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Sample records for ventricular myocardium studies

  1. Isolated Noncompaction of Ventricular Myocardium: a Magnetic Resonance Imaging Study of 11 Patients

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    Yun, Hong; Zeng, Meng Su; Jin, Hang; Yang, Shan [Zhongshan Hospital, Fudan University and Shanghai Medical Imaging Institute, Shanghai (China)

    2011-11-15

    To retrospectively summarize the cardiac magnetic resonance imaging (CMRI) findings of isolated noncompaction of ventricular myocardium (INVM). Eleven patients (M:F = 9:2; mean age, 35 years) were evaluated. Steady-state free precession (SSFP), fast spin echo (SE) sequence, SSFP cine imaging, and delayed enhanced inversion recovery spoiled gradient echo (IR-SPGR) sequence were used for showing abnormal myocardium, measuring ratio of noncompacted/compacted myocardium layers (NC/C ratio), and detecting myocardial viability. The left ventricle was divided into nine segments and a NC/C ratio > 2.3 in diastole was used as cutoff value in diagnosing left INVM. The right ventricle was assessed qualitatively. Cardiac MRI indicated left INVM in seven patients, right INVM in one patient and biventricle INVM in three patients. Characteristic CMRI changes included prominent trabeculations, deep intertrabecular recesses and an increase in the NC/C ratio. The most frequently involved segments was left ventricular apex. Three patients had abnormal high signals within the trabecular structures on SE T2 weighted image. One ventricular aneurysm and one apical thrombus were also observed. Delayed enhancement was seen in six of nine patients with subendocardial and transmural patterns. There are CMRI features that might be characteristic for INVM.

  2. Backscatter and attenuation characterization of ventricular myocardium

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    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  3. Biomechanical properties and microstructure of human ventricular myocardium.

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    Sommer, Gerhard; Schriefl, Andreas J; Andrä, Michaela; Sacherer, Michael; Viertler, Christian; Wolinski, Heimo; Holzapfel, Gerhard A

    2015-09-01

    In the multidisciplinary field of heart research it is of utmost importance to identify accurate myocardium material properties for the description of phenomena such as mechano-electric feedback or heart wall thickening. A rationally-based material model is required to understand the highly nonlinear mechanics of complex structures such as the passive myocardium under different loading conditions. Unfortunately, to date there are no experimental data of human heart tissues available to estimate material parameters and to develop adequate material models. This study aimed to determine biaxial extension and triaxial shear properties and the underlying microstructure of the passive human ventricular myocardium. Using new state-of-the-art equipment, planar biaxial extension tests were performed to determine the biaxial extension properties of the passive ventricular human myocardium. Shear properties of the myocardium were examined by triaxial simple shear tests performed on small cubic specimens excised from an adjacent region of the biaxial extension specimens. The three-dimensional microstructure was investigated through second-harmonic generation (SHG) microscopy on optically cleared tissues, which emphasized the 3D orientation and dispersion of the myofibers and adjacent collagen fabrics. The results suggest that the passive human LV myocardium under quasi-static and dynamic multiaxial loadings is a nonlinear, anisotropic (orthotropic), viscoelastic and history-dependent soft biological material undergoing large deformations. Material properties of the tissue components along local microstructural axes drive the nonlinear and orthotropic features of the myocardium. SHG microscopy investigation revealed detailed information about the myocardial microstructure due to its high resolution. It enabled the identification of structural parameters such as the fiber and the sheet orientations and corresponding dispersions. With this complete set of material data, a

  4. [Determination of iodine content in the left ventricular myocardium of healthy subjects using dual-source dual-energy CT myocardial first perfusion imaging: a preliminary study].

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    Chen, Z X; Wang, G; Liang, L; Lu, X R; Guo, Q H; Zhai, Y N; Shi, X N

    2017-05-24

    Objective: To analyze the normal value of the iodine content in the left ventricular myocardium of healthy subjects and to observe if there is a segmental differences on iodine distribution by using the second generation dual-source dual-energy computed tomography myocardial first perfusion imaging. Methods: In this retrospective study, 42 healthy subjects, who admitted to our department between January to June 2016, with normal second generation dual-source dual-energy computed tomography and coronary CT angioghphy (CTA), electrocardiogram (ECG) results, normal cardiac, hepatic, renal function, normal myocardial enzymes results were enrolled, data from 38 out of 42 subjects with satisfactory image quality were analyzed using Siemens Dual Energy-Heart PBV image processing software.In accordance with the standards of the American Heart Association myocardial 17 fractionation method, content of iodine was measured at different segmental left ventricular myocardium and aorta (left coronary artery from the opening level). The standardized containing iodine value (nIC) was calculated. Results: The iodine content of left ventricular myocardium in normal subjects was 3.1-7.8 mg/ml.The nIC of myocardium from 1st to 17th segments was 0.28±0.06, 0.31±0.07, 0.30±0.07, 0.30±0.04, 0.28±0.04, 0.29±0.05, 0.29±0.01, 0.30±0.07, 0.31±0.07, 0.27±0.06, 0.28±0.08, 0.28±0.07, 0.29±0.08, 0.31±0.07, 0.27±0.06, 0.29±0.06 and 0.21±0.07, respectively.The nIC of the 17th segment was the lowest and was significantly lower than in other segments (all PnIC was similar among the rest 16 segments (all P>0.05). Conclusion: The normal iodine content range in left ventricle myocardium is 3.1-7.8 mg/ml, and the lowest iodine content is detected in the apex and which is significantly lower than the other left ventricular segments.

  5. Left ventricular aneurysm associated with isolated noncompaction of the ventricular myocardium.

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    Sato, Yuichi; Matsumoto, Naoya; Yoda, Shunichi; Inoue, Fumio; Kunimoto, Satoshi; Fukamizu, Seiji; Tani, Shigemasa; Takayama, Tadateru; Tokai, Kotaro; Kasamaki, Yuji; Saito, Satoshi; Uchiyama, Takahisa; Koyama, Yasushi

    2006-05-01

    A 66-year-old woman was admitted to our hospital because of left ventricular failure and nonsustained ventricular tachycardia. Two-dimensional echocardiography demonstrated prominent trabeculations and deep intertrabecular recesses, findings consistent with noncompaction of the ventricular myocardium. Myocardial perfusion scintigraphy demonstrated a defect in the anterobasal left ventricular segment. Coronary angiogram was normal, but the left ventriculogram showed an aneurysm in the anterior myocardial segments. This is the first reported case with isolated noncompaction of the ventricular myocardium associated with left ventricular aneurysm.

  6. Absence of Borrelia burgdorferi in the myocardium of subjects with normal left ventricular systolic function: a study using PCR and electron microscopy.

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    Kuchynka, Petr; Palecek, Tomas; Grus, Tomas; Lindner, Jaroslav; Berenova, Dagmar; Kurzova, Zuzana; Balatova, Pavla; Krsek, Daniel; Vitkova, Ivana; Nemecek, Eduard; Podzimkova, Jana; Danek, Anna Barbara; Linhart, Ales

    2016-03-01

    Several studies have demonstrated the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with dilated cardiomyopathy (DCM). To further support a causal relationship between the presence of Bb in the heart muscle and the development of DCM, demonstration of the absence of Bb in the myocardium of subjects with normal left ventricular (LV) systolic function is needed. To determine the prevalence of Bb by polymerase chain reaction (PCR) and electron microscopy (EM) in individuals with normal LV systolic function and no history suggestive of myocarditis. We investigated 50 patients (67 ± 9 years, 15 women) with normal LV ejection fraction (EF) ≥ 50% undergoing cardiac surgery. During surgery, four samples from the right atrial appendage were obtained and subsequently examined by PCR and EM for the presence of Bb, and by immunohistochemistry to detect inflammatory cells. Serological testing of antibodies against Bb was also performed. Neither PCR nor EM detected Bb in any of the subjects. Immunohistological examination revealed myocardial inflammation in 2 individuals (4%). Serological analysis by enzyme-linked immunosorbent assay demonstrated IgM antibodies against Bb in 4% and IgG antibodies in 12% of the study cohort; Western blot revealed IgM as well as IgG positivity in 14% of patients. The absence of Bb in the myocardium of individuals who undergo cardiac surgery and have normal LV systolic function supports the idea of Bb pathogenicity in the development of DCM.

  7. Distinct microRNA expression signatures in human right atrial and ventricular myocardium.

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    Zhang, Yangyang; Wang, Xiaowei; Xu, Xiaohan; Wang, Jun; Liu, Xiang; Chen, Yijiang

    2012-12-01

    Human atrial and ventricular myocardium has distinct structure and physiology. MicroRNAs (miRNAs) are the central players in the regulation of gene expression, participating in many physiological processes. A comprehensive knowledge of miRNA expression in the human heart is essential for the understanding of myocardial function. The aim of this study was to compare the miRNA signature in human right atrial and ventricular myocardium. Agilent human miRNA arrays were used to indicate the miRNA expression signatures of the right atrial (n = 8) and ventricular (n = 9) myocardium of healthy individuals. Quantitative reverse transcription-polymerase chain reactions (qRT-PCRs) were used to validate the array results. DIANA-mirPath was used to incorporate the miRNAs into pathways. MiRNA arrays showed that 169 miRNAs were expressed at different levels in human right atrial and ventricular myocardium. The unsupervised hierarchical clustering analysis based on the 169 dysregulated miRNAs showed that miRNA expression categorized two well-defined clusters that corresponded to human right atrial and ventricular myocardium. The qRT-PCR results correlated well with the microarray data. Bioinformatic analysis indicated the potential miRNA targets and molecular pathways. This study indicates that distinct miRNA expression signatures in human right atrial and ventricular myocardium. The findings provide a novel understanding of the molecular differences between human atrial and ventricular myocardium and may establish a framework for an anatomically detailed evaluation of cardiac function regulation.

  8. [Research of different expressions of microRNA in sinus node, atrial myocardium, and ventricular myocardium of mouse].

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    Fang, Yibing; Wen, Zhi; Deng, Mingbin; Lai, Qiancheng; Yu Fengxu; Tang, Xiaolun; Wu, Changxue; Mu, Guangrong; Liao, Bin

    2014-09-01

    To study microRNA (miRNA) involved in the regulation of sinus cell differentiation by comparing sinus node, atrial myocardium, and ventricular myocardium specific miRNA expression profile differences in Kunming mice. A total of 180 Kunming mice, aged 60-90 days and weighing 35-45 g, were selected without gender differences after the method of anatomical localization for sinus node had been confirmed by preliminary experiments in another 10 Kunming mice. All the sinus node, atrial myocardium, and ventricular myocardium tissue from 180 mice were dissected and frozen by liquid nitrogen. The structure of tissue was observed by HE staining. Total RNA were extracted and quality-controlled before hybridize with miRNA chip. The chips with miRNA were used to screen specific miRNAs; and correlation analysis of gene function was done. The area of mice sinus node located at juncture of the superior vena cava and the right atrium junction with crista as its longitudinal axis, ranged 2.0 mm x 1.5 mm x 1.0 mm. HE staining showed the sinus cells were less, with no stripes, lightly stained cytoplasm, large and round nucleus, and there were much fibrous connective tissue around cells with a visible sinus node artery. The miRNA microarray results showed that compared with atrial myocardium and ventricular myocardium, there were 39 differentially expressed miRNAs in sinus node, including 12 up-regulated miRNAs and 27 down-regulated miRNAs. Based on the regulatory networks of differential miRNA and target gene, the regulatory miRNA was obtained. The differentially expressed miRNA in mice sinus node possibly may be involved in the regulation of sinus cell differentiation.

  9. Computerized mapping of fibrillation in normal ventricular myocardium

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    Chen, Peng-Sheng; Garfinkel, Alan; Weiss, James N.; Karagueuzian, Hrayr S.

    1998-03-01

    It is well known that the ability to fibrillate is intrinsic to a normal ventricle that exceeds a critical mass. The questions we address are how is ventricular fibrillation (VF) initiated and perpetuated in normal myocardium, and why is VF not seen more often in the general population if all ventricles have the ability to fibrillate. To study the mechanisms of VF, we used computerized mapping techniques with up to 512 channels of simultaneous multisite recordings for data acquisition. The data were then processed for dynamic display of the activation patterns and for mathematical analyses of the activation intervals. The results show that in normal ventricles, VF can be initiated by a single strong premature stimulus given during the vulnerable period of the cardiac cycle. The initial activations form a figure-eight pattern. Afterward, VF will perpetuate itself without any outside help. The self-perpetuation itself is due to at least two factors. One is that single wave fronts spontaneously break up into two or more wavelets. The second is that when two wavelets intersect perpendicular to each other, the second wavelet is broken by the residual refractoriness left over from the first wavelet. Mathematical analyses of the patterns of activation during VF revealed that VF is a form of chaos, and that transition from ventricular tachycardia (VT) to VF occurs via the quasiperiodic route. In separate experiments, we found that we can convert VF to VT by tissue size reduction. The physiological mechanism associated with the latter transition appears to be the reduction of the number of reentrant wave fronts and wandering wavelets. Based on these findings, we propose that the reentrant wave fronts and the wandering wavelets serve as the physiological equivalent of coupled oscillators. A minimal number of oscillators is needed for VF to perpetuate itself, and to generate chaotic dynamics; hence a critical mass is required to perpetuate VF. We conclude that VF in normal

  10. Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance.

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    Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

    2015-06-01

    It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that

  11. Pharmacological effects on oscillatory afterpotentials in partially depolarized ventricular myocardium.

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    Albitz, R; Nilius, B

    1988-01-01

    Oscillatory afterpotentials induced by toxic concentrations of ouabain were studied in isolated papillary muscles from the right ventricular myocardium of guinea pigs. In partially depolarized muscles (22 mM extracellular K+) oscillatory afterpotentials (OAP) that follow action potentials can be described as nearly harmonic, periodical damped oscillation using a five parameter model. We measured the time course of the appearance and disappearance of ouabain-induced OAP under control conditions and modified by different pharmacological tools. Changes were quantified by the parameters of the model used. Adriamycin (50 microM) significantly delayed the time to the first OAP after administration of ouabain but also shortened the time necessary for recovery after a 30 min application of ouabain. Adriamycin also reduced the damping ratio of OAP but unlike caffeine (2 mM) it did not completely suppress OAP. The reduction of the extracellular Na+ concentration from 126 to 63 mM strikingly depressed OAP both in damping ratio and amplitude. Dexamethasone (2 microM) transiently depressed already developed OAP. The effects of adriamycin as well as Na+ reduction point to a contribution of a Na/Ca exchange in the generation of OAP. The effect of dexamethasone may refer to an involvement of eicosanoides in the generation of arrhythmogenic OAP.

  12. Coronary flow reserve in the remote myocardium predicts left ventricular remodeling following acute myocardial infarction.

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    Cheng, Rongchao; Wei, Guoqian; Yu, Longhao; Su, Zhendong; Wei, Li; Bai, Xiuping; Tian, Jiawei; Li, Xueqi

    2014-07-01

    Coronary flow reserve (CFR) in the non-infarcted myocardium is often impaired following acute myocardial infarction (AMI). However, the clinical significance of CFR in the non-infarcted myocardium is not fully understood. The objective of the present study was to assess whether a relationship exists between CFR and left ventricular remodeling following AMI. We enrolled 18 consecutive patients undergoing coronary intervention. Heart function was analyzed using real-time myocardial contrast echocardiography at one week and six months after coronary angioplasty. Ten subjects were enrolled as the control group and were examined using the same method at the same time to assess CFR. Cardiac troponin I (cTnI) levels were routinely analyzed to estimate peak concentration. CFR was 1.55±0.11 in the infarcted zone and 2.05±0.31 in the remote zone (p2.05). The levels of cTnI were higher in Group I compared to Group II on admission (36.40 vs. 21.38, p<0.05). Furthermore, left ventricular end diastolic volume was higher in Group I compared to Group II at six months following coronary angioplasty. Microvascular dysfunction is commonly observed in the remote myocardium. The CFR value accurately predicts adverse ventricular remodeling following AMI.

  13. Hypertrabeculated Left Ventricular Myocardium in Relationship to Myocardial Function and Fibrosis: The Multi-Ethnic Study of Atherosclerosis.

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    Kawel-Boehm, Nadine; McClelland, Robyn L; Zemrak, Filip; Captur, Gabriella; Hundley, W Gregory; Liu, Chia-Ying; Moon, James C; Petersen, Steffen E; Ambale-Venkatesh, Bharath; Lima, João A C; Bluemke, David A

    2017-09-01

    Purpose To determine if excess greater left ventricle (LV) trabeculation is associated with decreased average regional myocardial function, diffuse fibrosis, or both. Materials and Methods This was a HIPAA-compliant institutional board approved multicenter study, and all participants provided written informed consent. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent a comprehensive cardiac magnetic resonance (MR) examination. LV trabeculation was measured with the maximal apical fractal dimension (FD), which is a marker of endocardial complexity. Demographic covariates, cardiovascular risk factors, and cardiac MR measurements were compared across quartiles of FD. Associations between FD and peak regional systolic circumferential strain (Ecc) and T1 time, a surrogate for diffuse myocardial fibrosis, were assessed with multivariable linear regression models. Results A total of 1123 subjects (593 [52.8%] female; mean age, 67.1 years ± 8.7 [standard deviation]) underwent FD and Ecc measurement, and 992 (521 [52.5%] female; mean age, 67.1 years ± 8.7) underwent FD and T1 measurement. Mean FD was 1.2 ± 0.07 in both groups, and mean Ecc was -18.3 ± 2.27 in the subjects who underwent FD and Ecc measurement. Global volumes and ejection fraction showed no differences between FD quartiles. However, with increasing FD quartile, Ecc was greater (indicating worse average regional function) (P myocardial strain (relative to the mean) per unit change in FD (regression coefficient = 4.0%; P < .001). There was no association between the degree of trabeculation and diffuse fibrosis measured with T1 mapping. Conclusion Average regional LV function was worse in individuals with greater LV trabeculation, supporting the concept of hypertrabeculation being an epiphenomenon of disease. © RSNA, 2017.

  14. Irx4 identifies a chamber-specific cell population that contributes to ventricular myocardium development.

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    Nelson, Daryl O; Jin, Dexter X; Downs, Karen M; Kamp, Timothy J; Lyons, Gary E

    2014-03-01

    The ventricular myocardium is the most prominent layer of the heart, and the most important for mediating cardiac physiology. Although the ventricular myocardium is critical for heart function, the cellular hierarchy responsible for ventricle-specific myocardium development remains unresolved. To determine the pattern and time course of ventricular myocardium development, we investigated IRX4 protein expression, which has not been previously reported. We identified IRX4+ cells in the cardiac crescent, and these cells were positive for markers of the first or second heart fields. From the onset of chamber formation, IRX4+ cells were restricted to the ventricular myocardium. This expression pattern persisted into adulthood. Of interest, we observed that IRX4 exhibits developmentally regulated dynamic intracellular localization. Throughout prenatal cardiogenesis, and up to postnatal day 4, IRX4 was detected in the cytoplasm of ventricular myocytes. However, between postnatal days 5–6, IRX4 translocated to the nucleus of ventricular myocytes. Given the ventricle-specific expression of Irx4 in later stages of heart development, we hypothesize that IRX4+ cells in the cardiac crescent represent the earliest cell population in the cellular hierarchy underlying ventricular myocardium development.

  15. Lesion dimensions during temperature-controlled radiofrequency catheter ablation of left ventricular porcine myocardium

    DEFF Research Database (Denmark)

    Høgh Petersen, H; Chen, X; Pietersen, Adrian

    1999-01-01

    the effect of catheter-tip length, ablation site, and convective cooling on lesion dimensions. METHODS AND RESULTS: In vitro strips of porcine left ventricular myocardium during different levels of convective cooling and in vivo pig hearts at 2 or 3 left ventricular sites were ablated with 2- to 12-mm...

  16. Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

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    Mario Torrado

    2010-01-01

    Full Text Available Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric remodeling remains largely elusive. To this end, we compared gene expression in the left (LV versus right ventricle (RV in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F and gene expression (PTPLAD1, JMJD1C, CEP290, which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV and volume (RV overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.

  17. Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

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    2011-01-01

    Background We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model. Methods Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h. Results In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05). Conclusion MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model. PMID:21244680

  18. Geometry-independent inclusion of basal myocardium yields improved cardiac magnetic resonance agreement with echocardiography and necropsy quantified left-ventricular mass.

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    Simprini, Lauren A; Goyal, Parag; Codella, Noel; Fieno, David S; Afroz, Anika; Mullally, Jamie; Cooper, Mitchell; Wang, Yi; Finn, John Paul; Devereux, Richard B; Weinsaft, Jonathan W

    2013-10-01

    Left-ventricular mass (LVM) is widely used to guide clinical decision-making. Cardiac magnetic resonance (CMR) quantifies LVM by planimetry of contiguous short-axis images, an approach dependent on reader-selection of images to be contoured. Established methods have applied different binary cut-offs using circumferential extent of left-ventricular myocardium to define the basal left ventricle (LV), omitting images containing lesser fractions of left-ventricular myocardium. This study tested impact of basal slice variability on LVM quantification. CMR was performed in patients and laboratory animals. LVM was quantified with full inclusion of left-ventricular myocardium, and by established methods that use different cut-offs to define the left-ventricular basal-most slice: 50% circumferential myocardium at end diastole alone (ED50), 50% circumferential myocardium throughout both end diastole and end systole (EDS50). One hundred and fifty patients and 10 lab animals were studied. Among patients, fully inclusive LVM (172.6±42.3g) was higher vs. ED50 (167.2±41.8g) and EDS50 (150.6±41.1g; both Pmyocardium, yields smallest CMR discrepancy with echocardiography-measured LVM and non-significant differences with necropsy-measured left-ventricular weight.

  19. Scrib:Rac1 interactions are required for the morphogenesis of the ventricular myocardium.

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    Boczonadi, Veronika; Gillespie, Rachel; Keenan, Iain; Ramsbottom, Simon A; Donald-Wilson, Charlotte; Al Nazer, Mariana; Humbert, Patrick; Schwarz, Robert J; Chaudhry, Bill; Henderson, Deborah J

    2014-10-01

    The organization and maturation of ventricular cardiomyocytes from the embryonic to the adult form is crucial for normal cardiac function. We have shown that a polarity protein, Scrib, may be involved in regulating the early stages of this process. Our goal was to establish whether Scrib plays a cell autonomous role in the ventricular myocardium, and whether this involves well-known polarity pathways. Deletion of Scrib in cardiac precursors utilizing Scrib(flox) mice together with the Nkx2.5-Cre driver resulted in disruption of the cytoarchitecture of the forming trabeculae and ventricular septal defects. Although the majority of mice lacking Scrib in the myocardium survived to adulthood, they developed marked cardiac fibrosis. Scrib did not physically interact with the planar cell polarity (PCP) protein, Vangl2, in early cardiomyocytes as it does in other tissues, suggesting that the anomalies did not result from disruption of PCP signalling. However, Scrib interacted with Rac1 physically in embryonic cardiomyocytes and genetically to result in ventricular abnormalities, suggesting that this interaction is crucial for the development of the early myocardium. The Scrib-Rac1 interaction plays a crucial role in the organization of developing cardiomyocytes and formation of the ventricular myocardium. Thus, we have identified a novel signalling pathway in the early, functioning, heart muscle. These data also show that the foetus can recover from relatively severe abnormalities in prenatal ventricular development, although cardiac fibrosis can be a long-term consequence. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  20. Late Gadolinium Enhancement of the right ventricular myocardium: Is it really different from the left ?

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    Macgowan Christopher K

    2008-05-01

    Full Text Available Abstract It has been suggested that, in late gadolinium enhancement, the signal of right ventricular myocardium is nulled at a shorter inversion time than the left. While we initially made the same observation, we believe that the difference is not real, but results from artifacts. We present 7 cases as well as computer simulations to describe the nature of these artifacts and explain how they can create the impression of different inversion times for the right and left ventricle. At inversion times that are shorter than ideal for the myocardium a black rim can be seen at the border of the myocardium with blood on the inside and with fat on the outside. This is most likely a partial volume effect. The thin myocardium of the right ventricle is sandwiched between these black rims and, at a low spatial resolution, is no longer visible. In this case, the adjacent black rims may then be misinterpreted as myocardium. While black rims also occur on the left side, the myocardium is thicker and remains discernable as a separate layer. As a consequence, the optimal inversion time for the right ventricle only appears different from that for the left. In fact, in the presence of hypertrophy of the right ventricle or during systolic wall thickening we did not find a difference in inversion times between the left and right ventricle. We conclude that sufficient spatial resolution is important for adequate late gadolinium enhancement of the right ventricle.

  1. Effect of ramipril on the electrophysiological characteristics of ventricular myocardium after myocardial infarction in rabbits.

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    Zhong, Ya; Cao, Ping; Tong, Chuanfeng; Li, Xia

    2012-05-01

    The current study aims to explore the effect of ramipril on the occurrence of ventricular arrhythmias and its possible mechanism after myocardial infarction (MI) in rabbits. A total of 24 rabbits were divided into three groups: the sham operation group (SHAM), the MI group, and the ramipril group (RAM). All groups were subjected to thoracotomy under sterile conditions; the MI and RAM groups underwent ligation of the left anterior descending coronary artery. On the second day after surgery, the RAM group was given ramipril (1 mg/kg per day). The rabbits in each group were fed for 12 weeks. The monophasic action potentials of the epicardium, mid-myocardium and endocardium in each group were, respectively, recorded before the MI and at 12 weeks after the MI. Meanwhile, the episodes of ventricular tachycardia or fibrillation (VT/VF) induced by procedure stimulations were counted, and the changes in L-type Ca flux (Ica-L) were recorded by means of the whole-cell patch-clamp technique. The episodes of VT/VF were decreased in the RAM group after MI. At 12 weeks after MI, the transmural dispersion of repolarization (TDR) in the MI group was prolonged significantly compared with the SHAM and RAM groups. The density of Ica-L in the MI group was significantly lower than that any other group. Ramipril manifestly decreases the incidence of VT/VF after MI in rabbits, and the mechanism may be associated with its inhibitory effect on electrical remodeling after MI.

  2. Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium

    National Research Council Canada - National Science Library

    Lowe, Martin D; Lynham, James A; Grace, Andrew A; Kaumann, Alberto J

    2002-01-01

    ... of (-)-isoprenaline and CGP12177 on ferret ventricular myocardium. (-)-CGP12177, (-)-pindolol and (-)-alprenolol were non-conventional partial agonists with intrinsic activity of 0.7, 0.2 and 0.1 respectively...

  3. Comparison of the affinity of [beta]-blockers for two states of the [beta]1-adrenoceptor in ferret ventricular myocardium

    National Research Council Canada - National Science Library

    Martin D Lowe; James A Lynham; Andrew A Grace; Alberto J Kaumann

    2002-01-01

    ... of (-)-isoprenaline and CGP12177 on ferret ventricular myocardium. (-)-CGP12177, (-)-pindolol and (-)-alprenolol were non-conventional partial agonists with intrinsic activity of 0.7, 0.2 and 0.1 respectively...

  4. Non-compaction of the ventricular myocardium: a cardiomyopathy in search of a pathoanatomical definition.

    Science.gov (United States)

    Val-Bernal, J Fernando; Garijo, M Francisca; Rodriguez-Villar, Diana; Val, Daniel

    2010-04-01

    Ventricular non-compaction is a rare cardiomyopathy characterized by numerous, excessively prominent ventricular trabeculations and deep intertrabecular recesses communicating with the ventricular cavity. The lesion is postulated to result from an intrauterine developmental arrest that stops compaction of the myocardial fiber meshwork. This cardiomyopathy affects the left ventricle, with or without concomitant right ventricular involvement. The disease is now seen with increasing frequency and it is clinically diagnosed by imaging techniques such as echocardiography or cardiac magnetic resonance. Current diagnostic criteria are considered too sensitive, particularly in black individuals. Therefore, this condition has generated considerable controversy and demands a new definition. Non-compaction cardiomyopathy shows variability of hereditary patterns, genetic heterogeneity, diversity in associated phenotypes and a wide spectrum of clinical presentation and pathophysiological findings. Non-compaction can be simply a variant of normal maturation of the ventricular myocardium with only the most severe forms producing a distinct clinical-pathological entity. Ventricular non-compaction most probably is a secondary consequence of an underlying molecular derangement produced by a pathogenetic mutation. It is likely that surgical pathologists will find this entity more frequently due to involvement in transplantation teams.

  5. The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.

    Science.gov (United States)

    Milani-Nejad, Nima; Canan, Benjamin D; Elnakish, Mohammad T; Davis, Jonathan P; Chung, Jae-Hoon; Fedorov, Vadim V; Binkley, Philip F; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2015-12-15

    Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization (P myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients. Copyright © 2015 the American Physiological Society.

  6. His bundle activates faster than ventricular myocardium during prolonged ventricular fibrillation.

    Science.gov (United States)

    Angel, Nathan; Li, Li; Dosdall, Derek J

    2014-01-01

    The Purkinje fiber system has recently been implicated as an important driver of the rapid activation rate during long duration ventricular fibrillation (VF>2 minutes). The goal of this study is to determine whether this activity propagates to or occurs in the proximal specialized conduction system during VF as well. An 8×8 array with 300 µm spaced electrodes was placed over the His bundles of isolated, perfused rabbit hearts (n = 12). Ventricular myocardial (VM) and His activations were differentiated by calculating Laplacian recordings from unipolar signals. Activation rates of the VM and His bundle were compared and the His bundle conduction velocity was measured during perfused VF followed by 8 minutes of unperfused VF. During perfused VF the average VM activation rate of 11.04 activations/sec was significantly higher than the His bundle activation rate of 6.88 activations/sec (pHis system activation rate (6.16, 5.53, 5.14, 5.22, 6.00, and 4.62 activations/sec significantly faster than the rate of the VM (4.67, 3.63, 2.94, 2.24, 3.45, and 2.31 activations/sec) (pHis system immediately decreased to 94% of the sinus rate during perfused VF then gradually decreased to 67% of sinus rhythm conduction at 8 minutes of unperfused VF. During prolonged VF the activation rate of the His bundle is faster than that of the VM. This suggests that the proximal conduction system, like the distal Purkinje system, may be an important driver during long duration VF and may be a target for interventional therapy.

  7. Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium

    Directory of Open Access Journals (Sweden)

    Amara eGreer-Short

    2015-02-01

    Full Text Available Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL prolongation (overdrive suppression and RCL shortening (overdrive excitation. The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25±4.0%, n=10 without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C produced significantly earlier excited beats (53±14%, n=5 with wider QRS durations (58±6.3%, n=5 than suppressed beats. Digoxin + hypothermia (0.75 M produced the most excited beats with significantly earlier RCL (44±3.2%, n=6 and wider QRS (60±3.1%, n=6 ratios relative to suppressed beats. Increasing pacing further shortened RCL (30±7.8%, n=6. In a prospective study, TTX (100 nM increased RCL ratio (15±6.0%, n=10 without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.

  8. In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI.

    Science.gov (United States)

    Kawel-Boehm, N; Dellas Buser, T; Greiser, A; Bieri, O; Bremerich, J; Santini, F

    2014-02-01

    To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 ± 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 ± 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 ± 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 ± 61 ms, and average T1 of the left-ventricular (LV) was 956 ± 25 ms (p myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV.

  9. Structurally-functional features of left ventricular myocardium and endothelial dysfunction in rheumatoid arthritis depending on presence of hypertension

    Directory of Open Access Journals (Sweden)

    E E Myasoedova

    2007-01-01

    Full Text Available Objective. To study the structure and functional peculiarities of left-ventricular myocardium and endothelial dysfunction in rheumatoid arthritis (RA in connection with the course of disease, concomitant arterial hypertension (AH and cardiovascular risk factors. Material and methods. Before the beginning of regular antihypertensive therapy we observed 55 pts with RA, 30 of them had mild or moderate AH developed in the course of RA and 36 pts with essential hypertension (EH without rheumatic diseases. Wfe evaluated anamnesis, blood pressure level (BPL, echocardiography data, endothelial vasodilation capacity and endothelial dysfunction index. All pts were purely comparable in age; RA with AH pts and EH pts — in BPL, anamnesis duration, SCORE-risk. No one of the observed persons had associated clinical states. 26 healthy subjects made control group. Results. RA with AH pts in comparison with EH had marked left-ventricular hypertrophy. Concentric hypertrophy prevailed in RA. 65,3% of RA-pts had diastolic dysfunction type 1. Endothelial dysfunction in RA-pts was found more often (in 57,9% individuals with RA and normal BPL and in 50% pts with RA and concomitant AH (p<0,05 than in EH-pts (20%. Thus, left-ventricular hypertrophy in RA optionally depended on AH presence but it is closely connected with metabolic (hyperlipidemia, abdominal obesity and endocrine (menopause disorders in pts with chronic autoimmune inflammation.

  10. A cellular automaton model for the ventricular myocardium considering the layer structure

    Science.gov (United States)

    Deng, Min-Yi; Dai, Jing-Yu; Zhang, Xue-Liang

    2015-09-01

    A cellular automaton model for the ventricular myocardium considering the layer structure has been established. The three types of cells in this model differ principally in the repolarization characteristics. For the normal travelling waves in this model, the computer simulation results show the R, S, and T waves and they are qualitatively in agreement with the standard electrocardiograph. Phenomena such as the potential decline of point J and segment ST and the rise of the potential line after the T wave appear when the ischemia occurs in the endocardium. The spiral wave has also been simulated, and the corresponding potential has a lower amplitude, higher frequency, and wider R wave, which accords with the distinguishing feature of the clinical electrocardiograph. Mechanisms underlying the above phenomena are analyzed briefly. Project supported by the National Natural Science Foundation of China (Grant Nos. 11365003 and 11165004).

  11. Noncompaction of the Ventricular Myocardium Is Associated with a De Novo Mutation in the β-Myosin Heavy Chain Gene

    Science.gov (United States)

    Budde, Birgit S.; Binner, Priska; Waldmüller, Stephan; Höhne, Wolfgang; Blankenfeldt, Wulf; Hassfeld, Sabine; Brömsen, Jürgen; Dermintzoglou, Anastassia; Wieczorek, Marcus; May, Erik; Kirst, Elisabeth; Selignow, Carmen; Rackebrandt, Kirsten; Müller, Melanie; Goody, Roger S.; Vosberg, Hans-Peter; Nürnberg, Peter; Scheffold, Thomas

    2007-01-01

    Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the α- and β-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium. PMID:18159245

  12. Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene.

    Directory of Open Access Journals (Sweden)

    Birgit S Budde

    Full Text Available Noncompaction of the ventricular myocardium (NVM is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the alpha- and beta-myosin heavy chain, respectively were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T. In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA and atrial septal defect (ASD. A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium.

  13. Late enhancement of the left ventricular myocardium in young patients with hypertrophic cardiomyopathy by electron beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Kenichi; Yoshibayashi, Muneo; Tsukano, Shinya; Ono, Yasuo; Arakaki, Yoshio; Naito, Hiroaki; Echigo, Shigeyuki [National Cardiovascular Center, Suita, Osaka (Japan)

    2001-05-01

    In the assessment of myocardial characteristics with computed tomography, late enhancement (intense stain in delayed phase image of contrast enhancement) is an abnormal finding and thought to represent fibrotic change. The purpose of this study was to investigate the clinical importance of late enhancement in young patients with hypertrophic cardiomyopathy. Forty-five patients with hypertrophic cardiomyopathy, aged 1 to 24 years, were examined by electron beam computed tomography. We also assessed the clinical data on these patients. Late enhancement was found in 29 (64%) patients, usually as a patchy, stained area in the myocardium. In 29 patients with late enhancement, seven (24%) has syncopal episode and seven (24%) had a family history of sudden death. In contrast, none (0%) of 16 patients without late enhancement had syncopal episode nor a family history of sudden death (p<0.05). Twenty-four hour electrocardiographic monitoring was performed for 31 patients. Al patients with ventricular tachycardia were in the group with late enhancement [10/23 (43%) vs 0/8 (0%), p<0.05]. Thirty-seven patients were examined by thallium scintigraphy. The perfusion defect was more frequently found in patients with late enhancement than in patients without [14/26 (54%) vs 2/11 (18%), p<0.05]. These data suggest that late enhancement shown with electron beam computed tomography is related to syncopal episode, family history of sudden death, ventricular tachycardia, and myocardial damage in young patients with hypertrophic cardiomyopathy. (author)

  14. Comparison of the affinity of β‐blockers for two states of the β1‐adrenoceptor in ferret ventricular myocardium

    National Research Council Canada - National Science Library

    Lowe, Martin D; Lynham, James A; Grace, Andrew A; Kaumann, Alberto J

    2002-01-01

    ... of (−)‐isoprenaline and CGP12177 on ferret ventricular myocardium. (−)‐CGP12177, (−)‐pindolol and (−)‐alprenolol were non‐conventional partial agonists with intrinsic activity...

  15. Postnatal myocardium remodelling generates inhomogeneity in the architecture of the ventricular mass.

    Science.gov (United States)

    Jouk, Pierre-Simon; Truong, Ba Luu; Michalowicz, Gabrielle; Usson, Yves

    2017-11-28

    The 3D architecture of the ventricular mass is poorly known, although in vivo imaging techniques show the physiological inhomogeneity of ventricular walls mechanics. Polarized light imaging makes it possible to quantitatively analyse the myosin filament orientation. In this paper, we focus on the study the 3D architecture and regional isotropy of myocardial cells. Twenty normal human hearts, 10 from the perinatal period and 10 from the post-neonatal period were studied by polarized light microscopy. In each voxel of the ventricular mass (90 × 90 × 500 µm) the principal orientation segment was automatically and unambiguously extracted as well as a regional isotropy index (regional orientation tensor of the voxel neighbourhood). During the first months of postnatal age, the median regional isotropy values decreased in the ventricular mesh. This global decrease was not homogeneous across the ventricular walls. From the perinatal to the neonatal period, this decrease was more marked in the inner two-third of the lateral left ventricular wall and in the right part of the interventricular septum. There was a progressive post-neonatal appearance of a particularly inhomogeneous secondary arrangement of myocardial cells with alternation of thick low-RI and thin high-RI areas. This study has shown a postnatal change in ventricular myocardial architecture, which became more inhomogeneous. The cell rearrangements responsible for the inhomogeneity in ventricular myocardial architecture are revealed by a variation of the regional isotropy index. These major changes are probably an adaptive consequence of the major haemodynamic changes occurring after birth during the neonatal period that generates major parietal stress variations and parietal remodelling.

  16. Effect of myocardial revascularisation on left ventricular systolic function in patients with and without viable myocardium: should non-viable segments be revascularised?

    Science.gov (United States)

    Stipac, Alja Vlahovic; Stankovic, Ivan; Vidakovic, Radosav; Putnikovic, Biljana; Ilic, Ivan; Milicic, Biljana; Neskovic, Aleksandar N

    2013-12-01

    To assess the effect of surgical revascularisation on left ventricular (LV) systolic function in patients with viable and non-viable dysfunctional LV segments determined by low dose dobutamine stress echocardiography (DSE). Prospective observational cohort study. Single tertiary care centre. Consecutive patients referred to surgical revascularisation (n=115). DSE and surgical revascularisation. Functional recovery defined as increase in ejection fraction ≥ 5% 1 year after revascularisation in patients with and without viable myocardium (viability defined as improvement of contractility in ≥ 4 LV segments on DSE). The mean age, ejection fraction and wall motion score index (WMSi) of patients were 59 ± 9 years, 44 ± 9% and 1.82 ± 0.31, respectively. There was no difference between DSE positive and DSE negative patients for any of those parameters at baseline study (p>0.05 for all). After 12 months, the ejection fraction increased 11 ± 1% in patients with viable myocardium vs 7 ± 1% in patients without viable myocardium (p=0.002). Moreover, in patients with viable myocardium, the greatest increase of ejection fraction occurred 1 month after surgery (9 ± 1%), whereas in those patients with negative DSE the ejection fraction increased more gradually (2±1% after 1 month, p=0.002 between groups for 1 month vs preoperative value), but still improved after 12 months follow-up (pmyocardial revascularisation. Functional recovery continuously occurs throughout the first year after surgical treatment.

  17. Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes

    DEFF Research Database (Denmark)

    Larsen, Julie; Bushnell, Peter; Steffensen, John Fleng

    2017-01-01

    We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca(2+) release from the sarcoplasmic reticulum (SR) with ryanodine...... positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark...

  18. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    Science.gov (United States)

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  19. Non-compaction of the ventricular myocardium, a cardiomyopathy in search of a pathoanatomical definition

    OpenAIRE

    Val-Bernal, José Fernando; Garijo, M.F.; Rodriguez-Villar, Diana; Val, D.

    2010-01-01

    Ventricular non-compaction is a rare cardiomyopathy characterized by numerous, excessively prominent ventricular trabeculations and deep intertrabecular recesses communicating with the ventricular cavity. The lesion is postulated to result from an intrauterine developmental arrest that stops compaction of the myocardial fiber meshwork. This cardiomyopathy affects the left ventricle, with or without concomitant right ventricular involvement. The disease is now seen w...

  20. Quantification of Coupled Stiffness and Fiber Orientation Remodeling in Hypertensive Rat Right-Ventricular Myocardium Using 3D Ultrasound Speckle Tracking with Biaxial Testing.

    Directory of Open Access Journals (Sweden)

    Dae Woo Park

    Full Text Available Mechanical and structural changes of right ventricular (RV in response to pulmonary hypertension (PH are inadequately understood. While current standard biaxial testing provides information on the mechanical behavior of RV tissues using surface markers, it is unable to fully assess structural and mechanical properties across the full tissue thickness. In this study, the mechanical and structural properties of normotensive and pulmonary hypertension right ventricular (PHRV myocardium through its full thickness were examined using mechanical testing combined with 3D ultrasound speckle tracking (3D-UST. RV pressure overload was induced in Sprague-Dawley rats by pulmonary artery (PA banding. The second Piola-Kirchhoff stress tensors and Green-Lagrangian strain tensors were computed in the RV myocardium using the biaxial testing combined with 3D-UST. A previously established non-linear curve-fitting algorithm was applied to fit experimental data to a Strain Energy Function (SEF for computation of myofiber orientation. The fiber orientations obtained by the biaxial testing with 3D-UST compared well with the fiber orientations computed from the histology. In addition, the re-orientation of myofiber in the right ventricular free wall (RVFW along longitudinal direction (apex-to-outflow-tract direction was noticeable in response to PH. For normotensive RVFW samples, the average fiber orientation angles obtained by 3D-UST with biaxial test spiraled from 20° at the endo-cardium to -42° at the epi-cardium (Δ = 62°. For PHRV samples, the average fiber orientation angles obtained by 3D-UST with biaxial test had much less spiral across tissue thickness: 3° at endo-cardium to -7° at epi-cardium (Δ = 10°, P<0.005 compared to normotensive.

  1. Quantification of heart, pericardium, and left ventricular myocardium movements during the cardiac cycle for thoracic tumor radiotherapy.

    Science.gov (United States)

    Tong, Ying; Yin, Yong; Lu, Jie; Liu, Tonghai; Chen, Jinhu; Cheng, Pinjing; Gong, Guanzhong

    2018-01-01

    The purpose of this study was to quantify variations in the heart, pericardium, and left ventricular myocardium (LVM) caused by cardiac movement using the breath-hold technique. In this study, the electrocardiography-gated four-dimensional computed tomography (CT) images of 22 patients were analyzed, which were sorted into 20 phases (0-95%) according to the cardiac cycle. The heart, pericardium, and LVM were contoured on each phase of the CT images. The positions, volume, dice similarity coefficient (DSC) in reference to 0% phase, and morphological parameters (max 3D diameter, roundness, spherical disproportion, sphericity, and surface area) in different phases of the heart, pericardium, and LVM were analyzed, which were presented as mean ± standard deviation. The mean values of displacements along the X, Y, and Z axes respectively were as follows: 1.2 mm, 0.6 mm, and 0.6 mm for the heart; 0.5 mm, 0.4 mm, and 0.8 mm for the pericardium; and 1.0 mm, 4.1 mm, and 1.9 mm for the LVM. The maximum variations in volume and DSC respectively were 16.49%±3.85% and 10.08%±2.14% for the heart, 12.62%±3.94% and 5.20%±1.54% for the pericardium, and 24.23%±11.35% and 184.33%±128.61% for the LVM. The differences in the morphological parameters between the maximum and minimum DSC phases for the heart and pericardium were not significantly different ( p >0.05) but were significantly different for the LVM ( p <0.05). The volumetric and morphological variations of the heart were similar to those of pericardium, and all were significantly smaller than those of the LVM. This inconsistency in the volumetric and morphological variations between the LVM and the heart and pericardium indicates that special protection of the LVM should be considered.

  2. Quantification of heart, pericardium, and left ventricular myocardium movements during the cardiac cycle for thoracic tumor radiotherapy

    Directory of Open Access Journals (Sweden)

    Tong Y

    2018-01-01

    Full Text Available Ying Tong,1,2 Yong Yin,1 Jie Lu,1 Tonghai Liu,1 Jinhu Chen,1 Pinjing Cheng,2 Guanzhong Gong1 1Department of Radiation Physics, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, 2School of Nuclear Science and Technology, University of South China, Hengyang, People’s Republic of China Purpose: The purpose of this study was to quantify variations in the heart, pericardium, and left ventricular myocardium (LVM caused by cardiac movement using the breath-hold technique. Patients and methods: In this study, the electrocardiography-gated four-dimensional computed tomography (CT images of 22 patients were analyzed, which were sorted into 20 phases (0–95% according to the cardiac cycle. The heart, pericardium, and LVM were contoured on each phase of the CT images. The positions, volume, dice similarity coefficient (DSC in reference to 0% phase, and morphological parameters (max 3D diameter, roundness, spherical disproportion, sphericity, and surface area in different phases of the heart, pericardium, and LVM were analyzed, which were presented as mean ± standard deviation. Results: The mean values of displacements along the X, Y, and Z axes respectively were as follows: 1.2 mm, 0.6 mm, and 0.6 mm for the heart; 0.5 mm, 0.4 mm, and 0.8 mm for the pericardium; and 1.0 mm, 4.1 mm, and 1.9 mm for the LVM. The maximum variations in volume and DSC respectively were 16.49%±3.85% and 10.08%±2.14% for the heart, 12.62%±3.94% and 5.20%±1.54% for the pericardium, and 24.23%±11.35% and 184.33%±128.61% for the LVM. The differences in the morphological parameters between the maximum and minimum DSC phases for the heart and pericardium were not significantly different (p>0.05 but were significantly different for the LVM (p<0.05. Conclusion: The volumetric and morphological variations of the heart were similar to those of pericardium, and all were significantly smaller than those of the LVM. This inconsistency in the volumetric and

  3. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    Science.gov (United States)

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (pmyocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  4. Global intracoronary infusion of allogeneic cardiosphere-derived cells improves ventricular function and stimulates endogenous myocyte regeneration throughout the heart in swine with hibernating myocardium.

    Directory of Open Access Journals (Sweden)

    Gen Suzuki

    Full Text Available Cardiosphere-derived cells (CDCs improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the "stop-flow" technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25. CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼ 33 × 10(6 icCDCs. Global icCDC infusion was safe and while ∼ 3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23 ± 6 to 51 ± 5% (p<0.01. In diseased hearts, myocyte proliferation (phospho-histone-H3 increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.

  5. Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium.

    Science.gov (United States)

    Katzung, B G; Morgenstern, J A

    1977-01-01

    Automaticity was induced in isolated guinea pig and cat papillary muscles by application of depolarizing constant current pulses. Increasing extracellular potassium from 1 to 15 mM caused a shift of pacemaker-like activity to less negative diastolic potentials and a decrease in maximum phase 4 slope. Membrane resistance, estimated from the relation of applied current to maximum diastolic potential, decreased when extracellular potassium was increased. Voltage clamps of cat papillary muscle demonstrated that action potentials activate a time-dependent outward current which has a reversal potential of -79.1 mV (+/- 0.99 SE, n = 20) at an extracellular potassium concentration of 5 mM. The reversal potential of this current varies with extracellular K+ with a slope of 50-60 mV per 10-fold concentration change. The current is activated by voltage clamps or action potential plateaus in the range of -30 to +30 mV. It has a time constant of deactivation which increases from approximately 100 to over 400 msec as clamp potential is increased from -90 to -60 mV. It is proposed that this current is equivalent to Ix1 demonstrated in other cardiac tissues and is responsible, in combination with inward currents, for automaticity in ventricular fibers.

  6. Effects of a new antiarrhythmic drug SS-68 on electrical activity in working atrial and ventricular myocardium of mouse and their ionic mechanisms

    Directory of Open Access Journals (Sweden)

    Saida K. Bogus

    2015-08-01

    Full Text Available SS-68 is a derivative of indole, which demonstrated strong antiarrhythmic effects not associated with significant QT prolongation in dog models of atrial fibrillation. Therefore, SS-68 was proposed as a new antiarrhythmic drug and the present study is the first describing its effects on action potentials (APs configuration and elucidating the ionic mechanisms of these effects. Sharp microelectrodes were used to record APs in isolated preparations of mouse atrial and ventricular myocardium. In both types of myocardium 10−6 M SS-68 produced reduction of AP duration, 3 × 10−6 M failed to alter AP waveform and 10−5 – 3 × 10−5 M prolonged APs. Sensitivity of main ionic currents to SS-68 was determined using whole-cell patch clamp. Transient potassium current Ito was slightly inhibited by SS-68 with IC50 = 1.43 × 10−4 M. IKur was more sensitive with IC50 = 1.84 × 10−5 M. Background inward rectifier showed very low sensitivity to SS-68 – only 10−4 M SS-68 caused significant reduction of IK1. ICaL was significantly inhibited by 10−6M – 3 × 10−5 M SS-68. The IC50 value for the ICaL was 1.84 × 10−6 M. Thus, main ionic currents of mouse cardiomyocytes are inhibited by SS-68 in the following order of potency: ICaL > IKur > Ito > IK1. While lower concentration of SS-68 shorten APs via suppression of ICaL, higher concentrations inhibit K+-currents leading to APs prolongation.

  7. Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

    Science.gov (United States)

    Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven; Motiwala, Shweta R; Addae, Gifty; Manning, Warren J; Nezafat, Reza

    2017-10-01

    To compare remote myocardium native T1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T1 map was performed using a slice interleaved T1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. The remote myocardium native T1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P infarct size had a moderate correlation with reduced LV ejection fraction (r = -0.33, P infarct size. Native T1 time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081. © 2017 International Society for Magnetic Resonance in Medicine.

  8. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

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    D.V. Vassallo

    2008-09-01

    Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

  9. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium.

    Science.gov (United States)

    Remme, C A; Verkerk, A O; Hoogaars, W M H; Aanhaanen, W T J; Scicluna, B P; Annink, C; van den Hoff, M J B; Wilde, A A M; van Veen, T A B; Veldkamp, M W; de Bakker, J M T; Christoffels, V M; Bezzina, C R

    2009-09-01

    Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel disease.

  10. Extension of borderzone myocardium in postinfarction dilated cardiomyopathy.

    Science.gov (United States)

    Jackson, Benjamin M; Gorman, Joseph H; Moainie, Sina L; Guy, T Sloane; Narula, Navneet; Narula, Jagat; John-Sutton, Martin G; Edmunds, L Henry; Gorman, Robert C

    2002-09-18

    This study tests the hypothesis that hypocontractile, borderzone myocardium adjacent to an expanding infarct becomes progressively larger and more hypocontractile as remodeling continues. Early infarct expansion following anteroapical myocardial infarction (MI) is associated with progressive ventricular dilation and heart failure. The contribution of perfused, hypocontractile, borderzone myocardium to this process is unknown. Using a sheep model of anteroapical infarction, sonomicrometry array localization and serial microsphere injections were used to track changes in regional myocardial contractility, geometry, and perfusion. Eight sheep were studied before and after infarction and two, five, and eight weeks later. Thirty intertransducer chord lengths were analyzed to measure regional contractility and serial changes in regional geometry at end systole. Beginning as a narrow band of fully perfused hypocontractile myocardium adjacent to the infarction, borderzone myocardium extends to involve additional contiguous myocardium that progressively loses contractile function as the heart remodels. Three distinct myocardial zones develop as a result of transmural MI: infarct, borderzone (perfused but hypocontractile), and remote (perfused and normally functioning).This study demonstrates that hypocontractile, fully perfused borderzone myocardium extends to involve contiguous normal myocardium during postinfarction remodeling. This borderzone myocardium is a unique type of perfused, hypocontractile myocardium, which is distinct from hibernating or stunned myocardium. Preventing extension of borderzone myocardium by medical or surgical means offers the prospect of preventing late-onset heart failure following transmural expanding MIs.

  11. OSTEOPONTIN, INTERLEUKIN-15 AND DYSFUNCTION OF LEFT VENTRICULAR MYOCARDIUM IN HYPERTENSIVE PATIENTS WITH CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    O. M. Kovalyova

    2016-12-01

    Full Text Available Based on a survey of 108 patients with hypertension complicated by chronic heart failure, studied the connection concentration of osteopontin, interleukin-15 inserum and morpho-functional characteristics of the left ventricle of the heart. In patients with CHF osteopontin levels were significantly higher, it revealed a relationship between adverse LV filling state and knots in serum osteopontin, while the level of IL-15 did not show such a relationship. The results indicate the potential value of osteopontin as a biomarker for the diagnosis of CHF.

  12. Cesium blockade of delayed outward currents and electrically induced pacemaker activity in mammalian ventricular myocardium.

    Science.gov (United States)

    Meier, C F; Katzung, B G

    1981-05-01

    The effects of Cs+, 5-25 mM, were studied in cat and guinea pig papillary muscles using voltage clamp and current clamp techniques. In solutions containing normal K+, the major effects of Cs+ were depolarization of the resting potential and reduction of the delayed outward current (ixl) between -80 and -20 mV. Both inward and outward portions of the isochronal current voltage relation (l-s clamps) were reduced by extracellular Cs+. This resulted in a substantial reduction of inward rectification and, by subtraction from the normal I-V relationship, the definition of a Cs+-sensitive component of current. Under current clamp conditions, 5-10 mM Cs+ produced a dose-dependent slowing of repetitive firing induced by depolarization. At higher concentrations (25 mM) the resting potential was depolarized and repetitive activity could not be induced by further depolarization. However, release of hyperpolarizing pulses was followed by prolonged bursts of repetitive action potentials, suggesting partial reversal of blockade or participation of another pacemaker process. The experimental results and a numerical simulation show that under readily attainable conditions, reduction in an outward pacemaker current may slow pacemaker activity.

  13. A study of tropomyosin's role in cardiac function and disease using thin-filament reconstituted myocardium

    Science.gov (United States)

    Bai, Fan; Wang, Li

    2013-01-01

    Tropomyosin (Tm) is the key regulatory component of the thin-filament and plays a central role in the cardiac muscle's cooperative activation mechanism. Many mutations of cardiac Tm are related to hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular noncompaction (LVNC). Using the thin-filament extraction/reconstitution technique, we are able to incorporate various Tm mutants and protein isoforms into a muscle fiber environment to study their roles in Ca2+ regulation, cross-bridge kinetics, and force generation. The thin-filament reconstitution technique poses several advantages compared to other in vitro and in vivo methods: (1) Tm mutants and isoforms are placed into the real muscle fiber environment to exhibit their effect on a level much higher than simple protein complexes; (2) only the primary and immediate effects of Tm mutants are studied in the thin-filament reconstituted myocardium; (3) lethal mutants of Tm can be studied without causing a problem; and (4) inexpensive. In transgenic models, various secondary effects (myocyte disarray, ECM fibrosis, altered protein phosphorylation levels, etc.) also affect the performance of the myocardium, making it very difficult to isolate the primary effect of the mutation. Our studies on Tm have demonstrated that: (1) Tm positively enhances the hydrophobic interaction between actin and myosin in the “closed state”, which in turn enhances the isometric tension; (2) Tm's seven periodical repeats carry distinct functions, with the 3rd period being essential for the tension enhancement; (3) Tm mutants lead to HCM by impairing the relaxation on one hand, and lead to DCM by over inhibition of the AM interaction on the other hand. Ca2+ sensitivity is affected by inorganic phosphate, ionic strength, and phosphorylation of constituent proteins; hence it may not be the primary cause of the pathogenesis. Here, we review our current knowledge regarding Tm's effect on the actomyosin interaction

  14. Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium

    Science.gov (United States)

    Majumder, Rupamanjari; Engels, Marc C.; de Vries, Antoine A. F.; Panfilov, Alexander V.; Pijnappels, Daniël A.

    2016-04-01

    Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity.

  15. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium

    NARCIS (Netherlands)

    Remme, C.A.; Verkerk, A.O.; Hoogaars, W.M.H.; Aanhaanen, W.T.J.; Scicluna, B.P.; Annink, C.; van den Hoff, M.J.B.; Wilde, A.A.M.; van Veen, T.A.B.; Veldkamp, M.W.; de Bakker, J.M.T.; Christoffels, V.M.; Bezzina, C.R.

    2009-01-01

    Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and

  16. Molecular Remodeling of Left and Right Ventricular Myocardium in Chronic Anthracycline Cardiotoxicity and Post-Treatment Follow Up

    Science.gov (United States)

    Lenčová-Popelová, Olga; Jirkovský, Eduard; Mazurová, Yvona; Lenčo, Juraj; Adamcová, Michaela; Šimůnek, Tomáš; Geršl, Vladimír; Štěrba, Martin

    2014-01-01

    Chronic anthracycline cardiotoxicity is a serious clinical issue with well characterized functional and histopathological hallmarks. However, molecular determinants of the toxic damage and associated myocardial remodeling remain to be established. Furthermore, details on the different propensity of the left and right ventricle (LV and RV, respectively) to the cardiotoxicity development are unknown. Hence, the aim of the investigation was to study molecular changes associated with remodeling of the LV and RV in chronic anthracycline cardiotoxicity and post-treatment follow up. The cardiotoxicity was induced in rabbits with daunorubicin (3 mg/kg/week for 10 weeks) and animals were sacrificed either at the end of the treatment or after an additional 10 weeks. Daunorubicin induced severe and irreversible cardiotoxicity associated with LV dysfunction and typical morphological alterations, whereas the myocardium of the RV showed only mild changes. Both ventricles also showed different expression of ANP after daunorubicin treatment. Daunorubicin impaired the expression of several sarcomeric proteins in the LV, which was not the case of the RV. In particular, a significant drop was found in titin and thick filament proteins at both mRNA and protein level and this might be connected with persistent LV down-regulation of GATA-4. In addition, the LV was more affected by treatment-induced perturbations in calcium handling proteins. LV cardiomyocytes showed marked up-regulation of desmin after the treatment and vimentin was mainly induced in LV fibroblasts, whereas only weaker changes were observed in the RV. Remodeling of extracellular matrix was almost exclusively found in the LV with particular induction of collagen I and IV. Hence, the present study describes profound molecular remodeling of myocytes, non-myocyte cells and extracellular matrix in response to chronic anthracycline treatment with marked asymmetry between LV and RV. PMID:24804796

  17. Molecular remodeling of left and right ventricular myocardium in chronic anthracycline cardiotoxicity and post-treatment follow up.

    Directory of Open Access Journals (Sweden)

    Olga Lenčová-Popelová

    Full Text Available Chronic anthracycline cardiotoxicity is a serious clinical issue with well characterized functional and histopathological hallmarks. However, molecular determinants of the toxic damage and associated myocardial remodeling remain to be established. Furthermore, details on the different propensity of the left and right ventricle (LV and RV, respectively to the cardiotoxicity development are unknown. Hence, the aim of the investigation was to study molecular changes associated with remodeling of the LV and RV in chronic anthracycline cardiotoxicity and post-treatment follow up. The cardiotoxicity was induced in rabbits with daunorubicin (3 mg/kg/week for 10 weeks and animals were sacrificed either at the end of the treatment or after an additional 10 weeks. Daunorubicin induced severe and irreversible cardiotoxicity associated with LV dysfunction and typical morphological alterations, whereas the myocardium of the RV showed only mild changes. Both ventricles also showed different expression of ANP after daunorubicin treatment. Daunorubicin impaired the expression of several sarcomeric proteins in the LV, which was not the case of the RV. In particular, a significant drop was found in titin and thick filament proteins at both mRNA and protein level and this might be connected with persistent LV down-regulation of GATA-4. In addition, the LV was more affected by treatment-induced perturbations in calcium handling proteins. LV cardiomyocytes showed marked up-regulation of desmin after the treatment and vimentin was mainly induced in LV fibroblasts, whereas only weaker changes were observed in the RV. Remodeling of extracellular matrix was almost exclusively found in the LV with particular induction of collagen I and IV. Hence, the present study describes profound molecular remodeling of myocytes, non-myocyte cells and extracellular matrix in response to chronic anthracycline treatment with marked asymmetry between LV and RV.

  18. Ventricular myocardial architecture in marine fishes.

    Science.gov (United States)

    Sanchez-Quintana, D; Hurle, J M

    1987-03-01

    The fiber architecture of the ventricular myocardium has been studied in elasmobranch (Isurus oxyrhinchus, Galeorhinus galeus, Prionace glauca) and teleost (Xiphias gladius, Thunnus thynnus, Thunnus alalunga) fish species with hearts displaying mixed types of ventricular musculature (compact and trabecular). In all cases, the compact myocardium is organized in layers of fiber bundles with an orderly arrangement within the ventricular walls. The number of these layers appears to be dependent on the relative thickness of the compact myocardium. Differences in the pattern of myocardial fiber arrangement were observed among the different fish species. In elasmobranchs the compact myocardium at the level of the atrioventricular orifice is continuous with the trabeculated myocardium. Furthermore, in elasmobranchs the trabeculated myocardium displays a precise arrangement in arcuate trabeculae running from the auriculoventricular to the conoventricular orifices. In teleosts, the compact myocardium is independent of the trabeculated myocardium and a large number of fibers insert into the bulboventricular fibrous ring. The trabeculated myocardium in these species displays an anarchic arrangement except at the level of the bulboventricular orifice, where the fibers tend to be aligned longitudinally, also being inserted into the fibrous ring. Minor differences, consisting mainly of the presence of extra bundles of fibers, were also observed among different individuals of the same species. The possible relationship between myocardial fiber architecture and ventricular shape is discussed.

  19. Assessment of synchronization measures for effective ventricular support by using the shape memory alloy fibred artificial myocardium in goats.

    Science.gov (United States)

    Shiraishi, Y; Yambe, T; Saijo, Y; Sato, F; Tanaka, A; Yoshizawa, M; Sugai, T K; Kaneko, Y; Sato, Y; Uematsu, M; Umezu, M; Fujimoto, T; Masumoto, N; Liu, H; Baba, A; Konno, S; Tabayashi, K; Sasada, H; Homma, D

    2009-01-01

    Thromboembolic and haemorrhagic complications are the primary causes of mortality and morbidity in patients with artificial hearts, which are known to be induced by the interactions between blood flow and artificial material surfaces. The authors have been developing a new mechanical artificial myocardial assist device by using a sophisticated shape memory alloy fibre in order to achieve the mechanical cardiac support from outside of the heart without a direct blood contacting surface. The original material employed as the actuator of artificial myocardial assist devices was 100um fibred-shaped, which was composed of covalent and metallic bonding structure and designed to generate 4-7 % shortening by Joule heating induced by the electric current input. In this study, we focused on the synchronization of the actuator with native cardiac function, and the phase delay parameter was examined in animal experiments using Saanen goats. Total weight of the device including the actuator was around 150g, and the electric power was supplied transcutaneously. The device could be successfully installed into thoracic cavity, which was able to be girdling the left ventricle. The contraction of the device could be controlled by the originally designed microcomputer. The mechanical contraction signal input had been transmitted with the phase delay of 50-200 msec after the R-wave of ECG, and hemodynamic changes were investigated. Cardiac output and systolic left ventricular pressure were elevated with 20% delay of cardiac cycle by 27% and 7%, respectively, although there was smaller difference under the condition of the delay of over 30%. Therefore, it was suggested that the synchronization measures should be examined in order to achieve sophisticated ventricular passive/active support on physiological demand.

  20. A three-dimensional finite element method for large elastic deformations of ventricular myocardium: I--Cylindrical and spherical polar coordinates.

    Science.gov (United States)

    Costa, K D; Hunter, P J; Rogers, J M; Guccione, J M; Waldman, L K; McCulloch, A D

    1996-11-01

    A three-dimensional Galerkin finite element method was developed for large deformations of ventricular myocardium and other incompressible, nonlinear elastic, anisotropic materials. Cylindrical and spherical elements were used to solve axisymmetric problems with r.m.s. errors typically less than 2 percent. Isochoric interpolation and pressure boundary constraint equations enhanced low-order curvilinear elements under special circumstances (69 percent savings in degrees of freedom, 78 percent savings in solution time for inflation of a thick-walled cylinder). Generalized tensor products of linear Lagrange and cubic Hermite polynomials permitted custom elements with improved performance, including 52 percent savings in degrees of freedom and 66 percent savings in solution time for compression of a circular disk. Such computational efficiencies become significant for large scale problems such as modeling the heart.

  1. Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes: smooth dogfish (Mustelus canis), sandbar shark (Carcharhinus plumbeus), and clearnose skate (Raja eglanteria).

    Science.gov (United States)

    Larsen, Julie; Bushnell, Peter; Steffensen, John; Pedersen, Morten; Qvortrup, Klaus; Brill, Richard

    2017-02-01

    We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca 2+ release from the sarcoplasmic reticulum (SR) with ryanodine and thapsigargin and measuring the resultant changes in contraction-relaxation parameters and the force-frequency relationship at 20 °C and 30 °C. We also examined ultrastructural differences with electron microscopy. In tissues from smooth dogfish, net force (per cross-sectional area) and measures of the speeds of contraction and relaxation were all higher in atrial than ventricular myocardium at both temperatures. Atrial-ventricular differences were evident in the other two species primarily in measures of the rates of contraction and relaxation. Ryanodine-thapsigargin treatment reduced net force and its maximum positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark at 30 °C; indicating that SR involvement in excitation-contraction (EC) coupling is species- and temperature-specific in elasmobranch fishes, as it is in teleost fishes. Atrial and ventricular myocardium from all three species displayed a negative force-frequency relationship, but there was no evidence that SR involvement in EC coupling was influenced by heart rate. SR was evident in electron micrographs, generally located in proximity to mitochondria and intercalated discs, and to a lesser extent between the myofibrils; with mitochondria being more numerous in ventricular than atrial myocardium in all three species.

  2. A study on the relationship between electrical transmural heterogeneity and ventricular energetics.

    Science.gov (United States)

    Hasegawa, Yuki; Mishima, Mitsuharu; Shimayoshi, Takao; Amano, Akira; Matsuda, Tetsuya

    2013-01-01

    In this study, we use cardiovascular simulation to gain new insights on the correlation between electrical heterogeneity and ventricular energetics. Although there are numerous in vivo and in vitro studies on the electrical heterogeneity within the ventricular myocardium, not much attention has been directed to its correlation to cardiovascular mechanics, because of difficulties in simultaneously observing and analyzing multiple spatial scales (the cell, the organ, and the system). We performed simulations with two cardiovascular simulation models, one which uses different myocardial cell models for the epicardial, endocardial, and mid-myocardial cells, and another which uses a homogeneous model throughout the entire myocardium. The epicardial, endocardial, and midmyocardial cell models were created by parametrically tuning a homogenous cell model. From the cardiovascular simulation we obtained pressure-volume loops which were used to calculate cardiovascular energetic efficiency and myocardial contractility. We found that energetic efficiency is higher in the electrically heterogeneous model.

  3. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    Science.gov (United States)

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  4. Left Ventricular Systolic Function Changes in Primary Hypertension Patients Detected by the Strain of Different Myocardium Layers

    Science.gov (United States)

    Huang, Jun; Yan, Zi-Ning; Rui, Yi-Fei; Fan, Li; Shen, Dan; Chen, Dong-Liang

    2016-01-01

    Abstract This study investigated left ventricular (LV) systolic dysfunction associated with differential strain among myocardial layers in primary hypertension (PH) patients with or without LV hypertrophy (LVH), and normal patients. In 63 PH and 42 healthy patients, two-dimensional speckle tracking echocardiography was used to measure the peak systolic longitudinal and circumferential strain of the myocardial subendocardial, middle and subepicardial layers, and the peak systolic radial strain. To assess LV systolic function, the apical long axis, 4- and 2-chamber views, and parasternal short axis at the basal, middle, and apical levels were acquired by cardiovascular ultrasound (Vivid E9, GE Healthcare, USA). Overall, the pattern in peak systolic longitudinal strain among myocardial layers was subendocardial > middle > subepicardial. In the peak systolic circumferential strain, this was middle > subepicardial > subendocardial. The peak systolic longitudinal strain was normal > NLVH > LVH. Among the groups, the peak systolic circumferential strain at the basal parasternal short-axis level was statistically similar, but at the middle and the apical parasternal short-axis levels were NLVH > normal > LVH. In normal and NLVH patients, the peak radial strain was middle > apical > basal, and in LVH patients was apical > middle > basal. The peak averages of the longitudinal and subendocardial circumferential strains differed significantly when LVH compared with NLVH and normal patients. The systolic function of PH patients was damaged in comparison with normal individuals, which could be detected conveniently and accurately using two-dimensional speckle tracking echocardiography. PMID:26765428

  5. No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

    Directory of Open Access Journals (Sweden)

    Nilgün Gedik

    Full Text Available Remote ischemic preconditioning (RIPC by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG. Activation of signal transducer and activator of transcription 5 (STAT5 in left ventricular (LV myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation or placebo (cuff deflated before skin incision (n = 10/10. Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline and at early (5-10 min reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002. Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12 complex, light chain 3 (LC3, parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02. STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05.Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

  6. The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig.

    Science.gov (United States)

    Grant, A O; Katzung, B G

    1976-02-01

    The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.

  7. Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle.

    Science.gov (United States)

    Blagonravov, M L; Korshunova, A Yu; Azova, M M; Bryk, A A; Frolov, V A

    2016-06-01

    The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

  8. Speckle-tracking echocardiography elucidates the effect of pacing site on left ventricular synchronization in the normal and infarcted rat myocardium.

    Directory of Open Access Journals (Sweden)

    Michal Mor

    Full Text Available BACKGROUND: Right ventricular (RV pacing generates regional disparities in electrical activation and mechanical function (ventricular dyssynchrony. In contrast, left ventricular (LV or biventricular (BIV pacing can improve cardiac efficiency in the setting of ventricular dyssynchrony, constituting the rationale for cardiac resynchronization therapy (CRT. Animal models of ventricular dyssynchrony and CRT currently relay on large mammals which are expensive and not readily available to most researchers. We developed a methodology for double-site epicardial pacing in conscious rats. Here, following post-operative recovery, we compared the effects of various pacing modes on LV dyssynchrony in normal rats and in rats with ischemic cardiomyopathy. METHODS: Two bipolar electrodes were implanted in rats as follows: Group A (n = 6 right atrial (RA and RV sites; Group B (n = 7 RV and LV sites; Group C (n = 8 as in group B in combination with left coronary artery ligation. Electrodes were exteriorized through the back. Following post-operative recovery, two-dimensional transthoracic echocardiography was performed during pacing through the different electrodes. Segmental systolic circumferential strain (Ecc was used to evaluate LV dyssynchrony. RESULTS: In normal rats, RV pacing induced marked LV dyssynchrony compared to RA pacing or sinus rhythm, as measured by the standard deviation (SD of segmental time to peak Ecc, SD of peak Ecc, and the average delay between opposing ventricular segments. LV pacing and, to a greater extend BIV pacing diminished the LV dyssynchrony compared to RV pacing. In rats with extensive MI, the effects of LV and BIV pacing were markedly attenuated, and the response of individual animals was variable. CONCLUSIONS: Rodent cardiac pacing mimics important features seen in humans. This model may be developed as a simple new tool to study the pathophysiology of ventricular dyssynchrony and CRT.

  9. Excitation-contraction coupling in zebrafish ventricular myocardium is regulated by trans-sarcolemmal Ca2+ influx and sarcoplasmic reticulum Ca2+ release.

    Science.gov (United States)

    Haustein, Moritz; Hannes, Tobias; Trieschmann, Jan; Verhaegh, Rabea; Köster, Annette; Hescheler, Jürgen; Brockmeier, Konrad; Adelmann, Roland; Khalil, Markus

    2015-01-01

    Zebrafish (Danio rerio) have become a popular model in cardiovascular research mainly due to identification of a large number of mutants with structural defects. In recent years, cardiomyopathies and other diseases influencing contractility of the heart have been studied in zebrafish mutants. However, little is known about the regulation of contractility of the zebrafish heart on a tissue level. The aim of the present study was to elucidate the role of trans-sarcolemmal Ca(2+)-flux and sarcoplasmic reticulum Ca(2+)-release in zebrafish myocardium. Using isometric force measurements of fresh heart slices, we characterised the effects of changes of the extracellular Ca(2+)-concentration, trans-sarcolemmal Ca(2+)-flux via L-type Ca(2+)-channels and Na(+)-Ca(2+)-exchanger, and Ca(2+)-release from the sarcoplasmic reticulum as well as beating frequency and β-adrenergic stimulation on contractility of adult zebrafish myocardium. We found an overall negative force-frequency relationship (FFR). Inhibition of L-type Ca(2+)-channels by verapamil (1 μM) decreased force of contraction to 22 ± 7% compared to baseline (n=4, pmyocardium (n=5, pmyocardium requires not only trans-sarcolemmal Ca2+-flux, but also intact sarcoplasmic reticulum Ca(2+)-cycling. In contrast to mammals, FFR is strongly negative in the zebrafish heart. These aspects need to be considered when using zebrafish to model human diseases of myocardial contractility.

  10. Lesion dimensions during temperature-controlled radiofrequency catheter ablation of left ventricular porcine myocardium: impact of ablation site, electrode size, and convective cooling

    DEFF Research Database (Denmark)

    Høgh Petersen, H; Chen, X; Pietersen, A

    1999-01-01

    It is important to increase lesion size to improve the success rate for radiofrequency ablation of ischemic ventricular tachycardia. This study of radiofrequency ablation, with adjustment of power to approach a preset target temperature, ie, temperature-controlled ablation, explores the effect of...

  11. Intracellular diglycerides in relation to glycaemic control in the myocardium: A pilot study in humans.

    Science.gov (United States)

    Anastasiou, C A; Stamatelopoulos, A; Dedeilias, P; Charitos, C; Sidossis, L S; Kavouras, S A

    2015-11-01

    Intramyocellular diglycerides have been implicated in the development of insulin resistance in skeletal muscle. In the myocardium, excess lipid storage may also contribute to the appearance of diabetic cardiomyopathy, while diglycerides may have certain cardio-protective functions. However, little is known on intracellular diglyceride accumulation in the human heart. We aimed to determine diglyceride accumulation in the human myocardium in relation to diabetes status. Six diabetic and six non-diabetic aged human subjects undergoing by-pass surgery participated in the study. Subjects were matched for age and body mass index. Intracellular diglyceride levels were measured in heart biopsy samples. Additional samples were taken from pectoralis major muscle that served as control. Whole body glycaemic control was assessed as the percent glycated haemoglobin. Intracellular diglycerides were significantly higher in the myocardium compared to pectoralis major (Pmyocardium. A linear negative correlation was observed between myocardial diglycerides and glycaemic control (r=0.632, P<0.05). Our data suggest that poor glycaemic control and diabetes may be associated with a defective accumulation of myocardial diglycerides, possibly blunting intracellular processes and contributing to the development of cardiomyopathy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Effects of droperidol on depolarization-induced automaticity, maximum upstroke velocity (Vmax) and the kinetics of recovery of Vmax in guinea-pig ventricular myocardium.

    Science.gov (United States)

    Grant, A O; Hondeghem, L M; Katzung, B G

    1978-04-01

    The neuroleptic drug droperidol has been shown to have clinically useful antiarrhythmic activity. Prior reports have resulted in conflicting conclusions regarding actions on ventricular myocardial fibers. The present study was carried out to determine whether droperidol did in fact affect the electrophysiological properties of guinea-pig papillary muscle fibers. By means of microelectrode recordings from preparations mounted in a single sucrose gap, the effects of concentrations from 10(-6) to 4 X 10(-5) M were studied on depolarization-induced automaticity, and on Vmax and its recovery time under several conditions of membrane potential, stimulation rate and external ion concentration. The results showed that at clinically relevant concentrations, droperidol significantly slows ventricular pacemaker activity, a depression reversible by epinephrine. Furthermore, Vmax was decreased and the time constant for Vmax recovery was significantly prolonged under several conditions which pertain to clinical arrhythmias, i.e., reduced membrane potential, elevated extracellular potassium concentrations and increased stimulation rate.

  13. NEUROHUMORAL CHANGES AND THE INDUCIBILITY OF VENTRICULAR TACHYCARDIAS - EFFECT OF EARLY REPERFUSION ON THE ISCHEMIC PORCINE MYOCARDIUM

    NARCIS (Netherlands)

    TIO, RA; DELANGEN, CDJ; MOOK, PH; BEL, KJ; WOLTERS, GTP; VANGILST, WH; DEGRAEFF, PA; WESSELING, H

    1992-01-01

    The effects of early reperfusion were studied in closed-chest pigs subjected to either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during early reperfusion and electrophysiological stability after two weeks were assessed. Coronary artery occlusion durations of 3 hr and early

  14. Arrhythmogenic right ventricular dysplasia

    OpenAIRE

    Bockeria O.L.; Lе T.G.

    2015-01-01

    Arrhythmogenic right ventricular dysplasia is a hereditary cardiomyopathy characterized by structural and functional disorders in the right ventricle, which results in ventricular arrhythmias. Arrhythmogenic right ventricular dysplasia is one of the important causes of sudden cardiac death in young people and athletes. Structural disorders in arrhythmogenic right ventricular dysplasia are associated with fibrosis and fatty infiltration of the right ventricular myocardium. These changes lead t...

  15. Left ventricular noncompaction: Clinical-echocardiographic study

    Directory of Open Access Journals (Sweden)

    Nikolić Aleksandra

    2012-01-01

    Full Text Available Background/Aim. Left ventricular noncompaction (LVNC is a disorder in endomyocardial morphogenesis, seen either isolated (in the absence of other cardiac anomalies or in association with congenital heart disease and some neuromuscular diseases. Intrauterine arrest of the compaction of myocardial fibers is postulated to be the reason of LVNC. Recognition of this condition is extremely important due to its high mortality and morbidity that lead to progressive heart failure, ventricular arrhythmias and thromboembolic events. The aim of this study was to determine the prevalence and clinical presentation of LVNC among consecutive outpatients according to clinical and echocardiographyic findings. Methode. A total of 3,854 consecutive patients examined at the Institute for Cardiovascular Diseases within a period January 2006 - January 2007 were included in the study. All the patients underwent echocardiographic examination using the same equipment (Vivid 7, GE Medical System. Echocardiographic parameters and clinical presentation in patients with echocardiographic criteria for LVNC were analyzed. Results. Analyzing 3,854 consecutive outpatients, using two-dimensional Color Doppler echocardiography from January 2006 to January 2007, 12 patients met the criteria for LVNC. Seven of them were male. The mean age at diagnosis was 45 ± 15 years. Analyzing clinical manifestation of LVNC it was found that seven patients had signs of heart failure, six had arrhythmias with no embolic events. Conclusion. Our results suggest that the real prevalence of LVNC may be higher than expected. New studies have to be done to solve this problem.

  16. Benefício da revascularização do miocárdio em pacientes com disfunção ventricular e músculo viável: remodelamento ventricular reverso e prognóstico The beneficial effect of revascularization on patients with severe left ventricular dysfunction and viable myocardium: reverse remodeling and prognosis

    Directory of Open Access Journals (Sweden)

    Gustavo Calado de Aguiar Ribeiro

    2005-06-01

    evolution showed diabetes, more than one myocardial infarction, and time interval between myocardial infarction and surgery were associated with worse prognosis. CONCLUSION: The benefits of myocardium revascularization in patients with viable muscle, as well as an improvement in the left ventricular ejection fraction, provide reverse remodeling, improvement in functional class and favorable long-term prognosis.

  17. Ventricular Energetics in Pediatric Left Ventricular Assist Device Patients: A Retrospective Clinical Study.

    Science.gov (United States)

    Di Molfetta, Arianna; Ferrari, Gianfranco; Iacobelli, Roberta; Filippelli, Sergio; Di Chiara, Luca; Guccione, Paolo; Amodeo, Antonio

    The aim of this study is to estimate the trend of right and left energetic parameters in left ventricular assist device (LVAD) pediatric patients. Echocardiographic data were retrospectively collected at the baseline, in the acute phase after and at the monthly follow-ups till the LVAD explantation to estimate left and right ventricular energetic parameters. A significant relationship between the left and right ventricular energetic parameter trends was found along all the study period. Left ventricular end-systolic pressure-volume relationship improved till the follow-up of 2 months and then progressively decreases. Left arteroventricular coupling decreases after the LVAD, and right arteroventricular coupling decreases at the short-term follow-up. Left ventricular external work, potential energy, and pressure-volume area decrease at the short-term follow-up and then increase progressively. Right ventricular external work, potential energy, and pressure-volume area increase after the LVAD implantation. Left (right) cardiac mechanical efficiency is improved (worsened) by the LVAD. Energetic variables show that the LVAD benefits could decrease over time. A continuous and patient tailored LVAD setting could contribute to prolong LVAD benefits. The introduction of energetic parameters could lead to a more complete evaluation of LVAD patients' outcome which is a multiparametric process.

  18. S100A4 protects the myocardium against ischemic stress.

    Science.gov (United States)

    Doroudgar, Shirin; Quijada, Pearl; Konstandin, Mathias; Ilves, Kelli; Broughton, Kathleen; Khalafalla, Farid G; Casillas, Alexandria; Nguyen, Kristine; Gude, Natalie; Toko, Haruhiro; Ornelas, Luis; Thuerauf, Donna J; Glembotski, Christopher C; Sussman, Mark A; Völkers, Mirko

    2016-11-01

    Myocardial infarction is followed by cardiac dysfunction, cellular death, and ventricular remodeling, including tissue fibrosis. S100A4 protein plays multiple roles in cellular survival, and tissue fibrosis, but the relative role of the S100A4 in the myocardium after myocardial infarction is unknown. This study aims to investigate the role of S100A4 in myocardial remodeling and cardiac function following infarct damage. S100A4 expression is low in the adult myocardium, but significantly increased following myocardial infarction. Deletion of S100A4 increased cardiac damage after myocardial infarction, whereas cardiac myocyte-specific overexpression of S100A4 protected the infarcted myocardium. Decreased cardiac function in S100A4 Knockout mice was accompanied with increased cardiac remodeling, fibrosis, and diminished capillary density in the remote myocardium. Loss of S100A4 caused increased apoptotic cell death both in vitro and in vivo in part mediated by decreased VEGF expression. Conversely, S100A4 overexpression protected cells against apoptosis in vitro and in vivo. Increased pro-survival AKT-signaling explained reduced apoptosis in S100A4 overexpressing cells. S100A4 expression protects cardiac myocytes against myocardial ischemia and is required for stabilization of cardiac function after MI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Improved myocardium transducer

    Science.gov (United States)

    Culler, V. H.; Feldstein, C.; Lewis, G. W.

    1979-01-01

    Method of implanting myocardium transducer uses special indented pins that are caught and securely held by epicardial fibers. Pins are small enough to cause minimum of trauma to myocardium during implantation or removal.

  20. Left ventricular function studied with MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Juergens, Kai Uwe; Fischbach, Roman [University of Muenster, Department of Clinical Radiology, Muenster (Germany)

    2006-02-01

    Accurate determination of left ventricular (LV) myocardial function is fundamental for clinical diagnosis, risk stratification, and estimation of prognosis in patients with ischemic and nonischemic cardiomyopathy. Primarily, multi-detector-row spiral CT (MDCT) of the heart aimed at detecting coronary artery obstruction and cardiac morphology. Multiple studies have demonstrated that retrospectively, ECG-gated MDCT determination of LV volumes and consequently global LV function parameters is feasible in good agreement with established imaging modalities such as cineventriculography, echocardiography, and cine magnetic resonance imaging (CMR). Post-processing tools allow fast and semi-automatic determination of LV function parameters from MDCT data in analogy to known CMR evaluation approaches. Although MDCT is not considered to be first-line modality for LV function assessment, this technique provides accessory dynamic information in patients undergoing MDCT coronary angiography, contributing to combined assessment of cardiac morphology and function without need of additional radiation exposure. MDCT regional LV wall motion analysis at rest is feasible, but further improvement in temporal resolution seems mandatory to match results obtained from competing modalities. This paper will discuss the diagnostic potential of MDCT for assessment of LV function with regards to accuracy and clinical applications, as well as limitations, particularly in comparison with CMR as modality of reference. (orig.)

  1. CT imaging features and frequency of left ventricular myocardial fat in patients with CT findings of chronic left ventricular myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Zafar, H.M.; Litt, H.I. [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Torigian, D.A. [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States)], E-mail: drew.torigian@uphs.upenn.edu

    2008-03-15

    Aim: To determine the frequency of left ventricular myocardial fat in patients with computed tomography (CT) findings of chronic left ventricular myocardial infarction, and to review the typical CT imaging features. Materials and methods: A retrospective search of the CT and nuclear scintigraphy reports from 1998-2005 for chronic left ventricular myocardial infarction was performed. The study group comprised those cases with available CT examinations revealing findings of chronic left ventricular myocardial infarction. Assessment for the presence of various imaging characteristics of left ventricular myocardial fat was performed in all cases. Results: The frequency of left ventricular myocardial fat in 47 patients with CT evidence of chronic left ventricular myocardial infarction was 51%. Typical CT imaging features include thin linear or curvilinear fat attenuation within left ventricular myocardium, most commonly subendocardial, often associated with left ventricular wall thinning and/or calcification, predominantly in elderly men. Conclusions: Fat in the left ventricular myocardium is a common additional finding in patients with CT findings of chronic left ventricular myocardial infarction. The potential, but as yet unproven, use of this CT imaging finding is that the radiologist may be able to suggest a potential diagnosis of chronic left ventricular myocardial infarction on unenhanced, thick-section, non-gated or non-triggered chest CT imaging where identification of myocardial wall thinning may be difficult.

  2. Histologic pathologies of the myocardium in septic shock: a prospective observational study.

    Science.gov (United States)

    Schmittinger, Christian A; Dünser, Martin W; Torgersen, Christian; Luckner, Günter; Lorenz, Ingo; Schmid, Stefan; Joannidis, Michael; Moser, Patrizia; Hasibeder, Walter R; Halabi, Milo; Steger, Christina M

    2013-04-01

    Myocardial depression in septic shock is well known, but its pathophysiological genesis is incompletely understood. To assess the incidence and extent of stress-induced histologic myocardial alterations in septic shock, a prospective, observational, combined clinical and postmortem study was conducted, and 20 patients dying from septic shock were included. Exclusion criteria were younger than 18 years, pregnancy, open heart surgery or cardiopulmonary resuscitation, acute neurologic diseases, pheochromocytoma, and forensic autopsy. A systematic macropathologic evaluation was performed. Nine predefined heart sections were histologically screened for myocytolysis, interstitial fibrosis, contraction band necrosis, mononuclear infiltrates, interstitial edema, and tissue hemorrhage. Stress-induced pathologies were found in 90% to 100% of patients in all heart sections (myocytolysis, 100%; interstitial fibrosis, 100%; contraction band necrosis, 95%; mononuclear infiltrates, 90%; interstitial edema, 90%; tissue hemorrhage, 30%). The incidence and extent of contraction band necrosis, mononuclear infiltrates, and myocytolysis did not differ between sexes; patients with or without chronic β-blocker, calcium antagonist, and/or statin premedication; or between the binary use of different catecholamine agents (all comparisons P > 0.05). The maximum epinephrine dose correlated with the overall extent of mononuclear infiltrates (Spearman-Rho, r = 0.704; P = 0.05) and myocytolysis (Spearman-Rho, r = 0.933; P = 0.001). Maximum norepinephrine doses correlated with the extent of mononuclear infiltrates in the left ventricular anterior wall (Spearman-Rho, r = 0.519; P = 0.02). The total duration of catecholamine therapy was correlated with the extent of mononuclear infiltrates in the apex (Spearman-Rho, r = 0.571; P = 0.009) and right atrium (Spearman-Rho, r = 0.535; P = 0.02). In conclusion, our results suggest that histologic lesions potentially indicative of stress

  3. Pathomorphological Changes of the Myocardium in Canine Dilated Cardiomyopathy (DCM

    Directory of Open Access Journals (Sweden)

    Janus Izabela

    2015-04-01

    Full Text Available The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration, vascular changes (congestion and coronary vessel wall hypertrophy, degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure, and presence of inflammatory infiltrates (mononuclear and polynuclear were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.

  4. Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction.

    Science.gov (United States)

    Aoki, Hirofumi; Matsunari, Ichiro; Nomura, Yusuke; Fujita, Wataru; Komatsu, Ryoko; Miyazaki, Yoshiharu; Nekolla, Stephan G; Kajinami, Kouji

    2013-07-01

    The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction. In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by (11)C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using (11)C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique. The (11)C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P infarcted myocardium (r = -0.561, P infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced (11)C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups. This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.

  5. Micro-Computed Tomography for the Quantitative 3-Dimensional Assessment of the Compact Myocardium in the Mouse Embryo.

    Science.gov (United States)

    Merchant, Samer S; Kosaka, Yasuhiro; Yost, H Joseph; Hsu, Edward W; Brunelli, Luca

    2016-07-25

    Ventricular non-compaction is characterized by a thin layer of compact ventricular myocardium and it is an important abnormality in the mouse heart. It is reminiscent of left ventricular non-compaction, a fairly common human congenital cardiomyopathy. Non-compaction in transgenic mice has been classically evaluated by measuring the thickness of the compact myocardium through histological techniques involving image analysis of 2-dimensional (D) sections. Given the 3D nature of the heart, the aim of this study was to determine whether a technique for the non-destructive, 3D assessment of the mouse embryonic compact myocardium could be developed. Micro-computed tomography (micro-CT), in combination with iodine staining, enabled the differentiation of the trabecular from the compact myocardium in wild-type mice. The 3D and digital nature of the micro-CT data allowed computation anatomical techniques to be readily applied, which were demonstrated via construction of group atlases and atlas-based descriptive statistics. Finally, micro-CT was used to identify the presence of non-compaction in mice with a deletion of the cell cycle inhibitor protein, p27(Kip1). Iodine staining-enhanced micro-CT with computational anatomical analysis represents a valid addition to classical histology for the delineation of compact myocardial wall thickness in the mouse embryo. Given the quantitative 3D resolution of micro-CT, these approaches might provide helpful information for the analysis of non-compaction. (Circ J 2016; 80: 1795-1803).

  6. Diabetes Mellitus-Induced Microvascular Destabilization in the Myocardium.

    Science.gov (United States)

    Hinkel, Rabea; Howe, Andrea; Renner, Simone; Ng, Judy; Lee, Seungmin; Klett, Katharina; Kaczmarek, Veronika; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Skroblin, Philipp; Mayr, Manuel; Milting, Hendrik; Dendorfer, Andreas; Reichart, Bruno; Wolf, Eckhard; Kupatt, Christian

    2017-01-17

    Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors. This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus. The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 10(12) viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tβ4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56. Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p myocardium. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus.

    Science.gov (United States)

    Ruparelia, Neil; Digby, Janet E; Jefferson, Andrew; Medway, Debra J; Neubauer, Stefan; Lygate, Craig A; Choudhury, Robin P

    2013-05-01

    Acute myocardial infarction (AMI) results in the recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone also becomes inflamed and is associated with adverse left ventricular remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function. Here, we tested the hypothesis that AMI results in remote organ (renal) inflammation. Mice were subjected to either AMI, sham procedure or no procedure and the inflammatory response in peripheral blood, injured and remote myocardium, and kidneys was studied at 24 h. AMI resulted in increased circulating neutrophils (P infarcted myocardium and in remote myocardium. VCAM-1 mRNA was increased in both infarcted and remote myocardium. VCAM-1 protein was also increased in the kidneys of AMI mice (P < 0.05) and immunofluorescence revealed localisation of VCAM-1 to glomeruli, associated with leukocyte infiltration and increased local inflammatory mRNA expression. We conclude that in addition to local inflammation, AMI results in remote organ inflammation evidenced by (1) increased expression of mRNA for inflammatory cytokines, (2) marked upregulation of VCAM-1 in renal glomeruli, and (3) the recruitment and infiltration of leukocytes in the kidney.

  8. Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.

    Science.gov (United States)

    Chen, C M; Gettes, L S; Katzung, B G

    1975-07-01

    We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.

  9. Arrhythmogenic right ventricular dysplasia: A case report

    Directory of Open Access Journals (Sweden)

    Tessa Negrín Valdés

    2015-10-01

    Full Text Available Arrhythmogenic right ventricular dysplasia is a heart muscle disease that predominantly affects the right ventricle, bringing about the replacement of normal myocardium with fatty or fibrofatty tissue and causing sudden death in young individuals. Ventricular tachycardia is an important clinical manifestation, although there are reports of right or global heart failure. The diagnosis is confirmed by echocardiography and magnetic resonance imaging. The case of a 65-year-old former smoker, with hypertension and ischemic heart disease, a history of effort syncope symptoms and proven non-sustained ventricular tachycardia, with morphology of left bundle branch block, is reported. Relevant diagnostic studies were performed, and echocardiographic elements which were compatible with arrhythmogenic right ventricular dysplasia were found. Therefore, an implantable cardioverter defibrillator was implanted, after which the patient has had a favorable outcome.

  10. Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Christensen, A H; Benn, M; Bundgaard, H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a lethal condition characterised by ventricular tachyarrhythmias, right and/or left ventricular involvement and fibrofatty infiltrations in the myocardium. The disease has been associated with mutations in genes encoding desmosomal proteins....

  11. Study of Left Ventricular Diastolic Function in Patients with Diabetes ...

    African Journals Online (AJOL)

    Left Ventricular Function: all controls had normal LV function. Studied patients had normal LV systolic function. A total of 29 patients (58%) were found to have LV diastolic dysfunction. Grade I LVDD was most common (40%). LVDD was significantly correlated with duration of DM and age of the patient (P<0.05). There was a ...

  12. Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs

    Directory of Open Access Journals (Sweden)

    Grins Edgars

    2005-04-01

    Full Text Available Abstract Background The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. Methods In an open chest porcine model (n = 17, myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. Results Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 ± 2.0 vs. 4.3 ± 1.5 (mean ± standard deviation, (p = 0.004. In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 ± 1.7 vs. 6.2 ± 2.0 (p = 0.027. Conclusion Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified.

  13. [Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

    Science.gov (United States)

    Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B

    2009-01-01

    The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.

  14. Advanced quantitative echocardiography in arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Hastrup Svendsen, Jesper; Sogaard, Peter

    2007-01-01

    BACKGROUND: Arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) is a regional disease of the RV myocardium with variable degrees of left ventricular involvement. Three-dimensional echocardiography and Doppler tissue imaging (DTI) are new echocardiographic modalities for the evaluation of ...

  15. Myocardial viability for decision-making concerning revascularization in patients with left ventricular dysfunction and coronary artery disease: a meta-analysis of non-randomized and randomized studies.

    Science.gov (United States)

    Orlandini, Andrés; Castellana, Noelia; Pascual, Andrea; Botto, Fernando; Cecilia Bahit, M; Chacon, Carolina; Luz Diaz, M; Diaz, Rafael

    2015-03-01

    Myocardial viability tests have been proposed as a key factor in the decision-making process concerning coronary revascularization procedures in patients with left ventricular dysfunction and coronary artery disease (LVD-CAD). We performed a systematic review and meta-analysis of studies that compared medical treatment with revascularization in patients with viable and non-viable myocardium and recorded mortality as outcome. Thirty-two non-randomized (4328 patients) and 4 randomized (1079 patients) studies were analyzed. In non-randomized studies, revascularization provided a significant mortality benefit compared with medical treatment (p<0.05). Since the heterogeneity was significant (p<0.05) a viability subgroup analysis was performed, showing that revascularization provided a significant mortality benefit compared with medical treatment in patients with viable myocardium (p<0.05) but not in patients without (p=0.34). There was a significant subgroup effect (p<0.05) related to the intensity of the effect, but not to the direction. In randomized studies, revascularization did not provide a significant mortality benefit compared with medical treatment in either patients with viable myocardium or those without (p=0.21). There was no significant subgroup effect (p=0.72). Neither non-randomized nor randomized studies demonstrated any significant difference in outcomes between patients with and without viable myocardium. The available data are inconclusive regarding the usefulness of myocardial viability tests for the decision-making process concerning revascularization in LVD-CAD patients. Patients with viable myocardium appear to benefit from revascularization, but similar benefits were observed in patients without viable myocardium. Moreover, a neutral or adverse effect of revascularization cannot be excluded in either group of patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Acute myocardial infarction: estimation of at-risk and salvaged myocardium at myocardial perfusion SPECT 1 month after infarction.

    Science.gov (United States)

    Romero-Farina, Guillermo; Aguadé-Bruix, Santiago; Candell-Riera, Jaume; Pizzi, M Nazarena; Pineda, Victor; Figueras, Jaume; Cuberas, Gemma; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David

    2013-11-01

    To estimate at-risk and salvaged myocardium by using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging after acute myocardial infarction (AMI). The study was approved by the hospital's Ethical Committee on Clinical Trials (trial register number, PR(HG)36/2000), and all patients gave informed consent. Forty patients (mean age, 61.78 years; eight women) with a first AMI underwent two gated SPECT examinations--one before percutaneous coronary intervention (PCI) and one 4-5 weeks after PCI. Myocardium at risk was estimated by assessing the perfusion defect at the first gated SPECT examination, and salvaged myocardium was estimated by assessing the risk area minus necrosis at the second examination. Myocardium at risk was estimated by determining the discordance between the areas of left ventricular (LV) wall motion and perfusion at the second examination. Concordance between tests was analyzed by means of linear regression analysis, the Pearson correlation, the intraclass correlation coefficient, and Bland-Altman analysis. An improvement in perfusion, wall motion, wall thickening, and LV ejection fraction (P Myocardial perfusion gated SPECT performed 1 month after early PCI in a first AMI provides potentially useful information on at-risk and salvaged myocardium. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122324/-/DC1. RSNA, 2013

  17. Application of a New Robust ECG T-Wave Delineation Algorithm for the Evaluation of the Autonomic Innervation of the Myocardium

    DEFF Research Database (Denmark)

    Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

    2016-01-01

    T-wave amplitude (TWA) is a well know index of the autonomic innervation of the myocardium. However, until now it has been evaluated only manually or with simple and inefficient algorithms. In this paper, we developed a new robust single-lead electrocardiogram (ECG) T-wave delineation algorithm......-up tilt caused a decrease of TWA and that metoprolol blunted this decrease. Through the development of a robust algorithm, this study opens the way for further research on the T-wave analysis for the assessment of the autonomic innervation of the ventricular myocardium....

  18. Chlorogenic acid a dietary polyphenol attenuates isoproterenol induced myocardial oxidative stress in rat myocardium: An in vivo study.

    Science.gov (United States)

    Akila, Palaniyandi; Vennila, Lakshmanan

    2016-12-01

    Intent of the present study has been made to appraise the cardioprotective effect of chlorogenic acid (CGA) on isoproterenol (ISO) induced myocardial infarction (MI) in male albino Wistar rats. ISO-induced myocardial damage was indicated by the elevated levels of marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHPs) were significantly increased in the plasma and heart tissue. Activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the non enzymic antioxidants like vitamin C, vitamin E and reduced glutathione (GSH) were decreased in the erythrocytes, plasma and heart tissue of the ISO-induced rats and myocardium infarct size as observed by staining with triphenyltetrazolium chloride (TTC). Histopathological observation corroborated with the bioochemical parameters. Oral administration of CGA at different doses (10, 20, 40mg/kg BW) for 19days prevented the above changes. The 40mg/kg BW of CGA was more pronounced than other two doses and brought back all the above parameters to near normalcy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability : A PET study

    NARCIS (Netherlands)

    Slart, Riemer H. J. A.; Agool, Ali; van Veldhuisen, Dirk J.; Dierckx, Rudi A.; Bax, Jeroen J.

    SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on

  20. [Head to head comparison of dobutamine alone and combined with nitrate stress echocardiography and 99mTc-MIBI/18FDG myocardial SPECT image for diagnosis of viable myocardium in patients with severe left ventricular dysfunction].

    Science.gov (United States)

    Yang, Yue-jin; Yang, Wei-xian; Shi, Rong-fang; Hu, Feng-huan; You, Shi-jie; Tian, Yue-qin; He, Zuo-xiang; Wang, Yan-wu; Ye, Ling; Chen, Ji-lin; Gao, Run-lin; Chen, Zai-jia

    2005-04-01

    This study was sought to compare the sensitivity, specificity and accuracy of (1) dual isotope simultaneous acquisition single-photon emission computed tomography (DISA SPECT) myocardial image with (99m)Tc-sestamibi/(18)F-fluorodeoxyglucose ((99m)Tc-MIBI/(18)FDG); (2) low dose dobutamine alone and combined with Isosorbide Dinitrate (ISDN: Isoket) stress two dimensional echocardiography (2DE) to predict regional movement recovery after revascularization (CRV) in patients with old myocardial infarction (OMI) and severe left ventricular dysfunction. Twenty-six patients (mean age 51 +/- 8 years, male 25, female 1) with OMI and severe left ventricular dysfunction (mean left ventricular ejection fraction, LVEF (38.6% +/- 4.9%) underwent low dose dobutamine 10 microg x kg(-1) x min(-1) (Dob10 microg) and ISDN (286 +/- 31 microg/min) combined with Dob5 microg (ISDN-Dob 5 microg) 2DE and DISA SPECT within one week. In echocardiogram and DISA SPECT images: the left ventricle (LV) was divided into 16 segments. The semi-quantitative scoring system was used for both images. Myocardial viability was defined as an improvement of at least >or= 1 grade in at least two contiguous segments at rest 2DE after CRV. The viable segments detecting rate with stress 2DE and DISA SPECT were compared. Compared with the results of post-CRV, the sensitivity, specificity and accuracy of detecting viable segments of two methods were calculated. Among 272 abnormal segments in 26 patients, 156 (57.4%) segments showed contractile improvement after CRV. The viable segments detecting rate with DISA SPECT was 72.4% (134/254), which was significantly higher than the contractile improved rate after CRV (P 0.05). With DISA SPECT, the sensitivity, specificity and accuracy were 93.7%, 55% and 76.8%, respectively. Compared with DISA SPECT, Dob10 microg 2DE showed similar sensitivity (88.6%), specificity (64.2%) and the accuracy (77.9%). When ISDN combined with Dob5 microg, the sensitivity (91.4%), specificity

  1. Left ventricular filling patterns in patients with systemic hypertension and left ventricular hypertrophy (the LIFE study). Losartan Intervention For Endpoint

    DEFF Research Database (Denmark)

    Wachtell, K; Smith, G; Gerdts, E

    2000-01-01

    Abnormal left ventricular (LV) filling may exist in early stages of hypertension. Whether this finding is related to LV hypertrophy is currently controversial. This study was undertaken to assess relations between abnormal diastolic LV filling and LV geometry in a large series of hypertensive pat...

  2. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  3. [MRI diagnosis of right ventricular dysplasia].

    Science.gov (United States)

    Sommer, T; Lewalter, T; Bierhoff, E; Pakos, E; von Smekal, A; Pauleit, D; Hofer, U; Lüderitz, B; Schild, H

    1998-12-01

    Right ventricular dysplasia (RVD) represents an important cause of sudden death and ventricular arrhythmias in young patients. The aim of this study was to describe diagnostic diagnostic criteria and the MR-tomographie aspects of the disease. 34 patients with clinically suspected RVD were examined by 0.5-T MRI (cardiac-gated T1-weighted spin echo sequences and cine gradient echo sequences). RVD was confirmed in 16 patients and ruled out in 18 patients. MR images were evaluated for presence of: 1. right myocardial fatty infiltration, 2. dilatation of the right ventricle, 3. dilatation of the right ventricular outflow tract, and 4. localised right ventricular aneurysm. Right myocardial fatty infiltration was detected by MRI in 11 of 16 patients (69%) with RVD. Dilatation of the right ventricle was seen in 5 patients, dilatation of the right outflow tract in one patient, and localised right ventricular aneurysm in two patients with RVD. MRI is able to demonstrate fatty replacement of right ventricular myocardium in most cases and plays an important role in the diagnosis of RVD.

  4. Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium.

    Science.gov (United States)

    Tachibana, Atsushi; Santoso, Michelle R; Mahmoudi, Morteza; Shukla, Praveen; Wang, Lei; Bennett, Mihoko; Goldstone, Andrew B; Wang, Mouer; Fukushi, Masahiro; Ebert, Antje D; Woo, Y Joseph; Rulifson, Eric; Yang, Phillip C

    2017-09-01

    Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through

  5. Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction.

    Science.gov (United States)

    Duncker, Dirk J; de Beer, Vincent J; Merkus, Daphne

    2008-05-01

    The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted beta-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of K(ATP) channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, alpha-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance.

  6. Mutation analysis of the candidate genes SCN1B-4B, FHL1, and LMNA in patients with arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Refsgaard, Lena; Olesen, Morten Salling; Møller, Daniel Vega

    2012-01-01

    INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart disease characterized by fibrofatty infiltrations in the myocardium, right and/or left ventricular involvement, and ventricular tachyarrhythmias. Although ten genes have been associated with ARVC...

  7. Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus.

    Science.gov (United States)

    Afanasiev, S A; Kondratieva, D S; Rebrova, T Yu; Batalov, R E; Popov, S V

    2016-01-01

    Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR) with diabetes mellitus (DM) animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes.

  8. Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    S. A. Afanasiev

    2016-01-01

    Full Text Available Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR with diabetes mellitus (DM animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes.

  9. Vegfa Impacts Early Myocardium Development in Zebrafish.

    Science.gov (United States)

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P; Li, Fen

    2017-02-21

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium-endocardium crosstalk.

  10. Diagnostic dilemmas: overlapping features of Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy

    NARCIS (Netherlands)

    Hoogendijk, Mark G.

    2012-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome are distinct clinical entities which diagnostic criteria exclude their coexistence in individual patients. ARVC is a myocardial disorder characterized by fibro-fatty replacement of the myocardium and ventricular arrhythmias.

  11. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction

    OpenAIRE

    Zhang, Dongze; Tu, Huiyin; Wang, Chaojun; Cao, Liang; Muelleman, Robert L.; Wadman, Michael C; Li, Yu-Long

    2017-01-01

    Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG ...

  12. Bioengineering Human Myocardium on Native Extracellular Matrix

    Science.gov (United States)

    Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

    2015-01-01

    Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable

  13. The quantification of dipyridamole induced changes in regional deformation in normal, stunned or infarcted myocardium as measured by strain and strain rate: an experimental study.

    Science.gov (United States)

    Marciniak, Maciej; Claus, Piet; Streb, Witold; Marciniak, Anna; Boettler, Petra; McLaughlin, Myles; D'hooge, Jan; Rademakers, Frank; Bijnens, Bart; Sutherland, George R

    2008-04-01

    Strain rate imaging (SRI) during dobutamine stress-echocardiography (DSE) has been shown to differentiate between ischemic substrates based on the segmental response. Dipyridamole stress echo (DIPSE) is currently used as an alternative to DSE in detecting coronary artery disease. The aim of this study was: (a) to determine the normal response in peak-systolic myocardial strain (S) and strain-rate (SR) during DIPSE and (b) to compare the S and SR responses of DSE and DIPSE in the same chronically ischemic/infarcted segments in the setting of single vessel disease. The deformation response to DIPSE was studied in 7 normal pigs and in an additional 18 pigs, with a spectrum of ischemic substrates. S and SR data were extracted from a posterior wall "at risk" segment at baseline and during both DSE and DIPSE. The animals were divided into different ischemic substrate (stunning, non-transmural and transmural infarction), based on the DSE response as previously suggested. In normal myocardium, dipyridamole induced no changes in regional systolic deformation neither during nor after the infusion. Furthermore there was no detectable response in S and SR in segments with either a non-transmural or a transmural infarction. However, in myocardial segments with a DSE "stunning response", both end systolic S and peak-systolic SR tended to "normalize" at peak dipyridamole dose. These results suggest that dipyridamole does not induce changes in regional deformation in normal or (partially) infarcted myocardium. Only in stunned myocardium (in the setting of single-vessel disease), dipyridamole tends to normalize deformation.

  14. Noncompaction myocardium in association with type Ib glycogen storage disease.

    Science.gov (United States)

    Goeppert, Benjamin; Lindner, Martin; Vogel, Monika Nadja; Warth, Arne; Stenzinger, Albrecht; Renner, Marcus; Schnabel, Philipp; Schirmacher, Peter; Autschbach, Frank; Weichert, Wilko

    2012-10-15

    Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four. Copyright © 2012 Elsevier GmbH. All rights reserved.

  15. Pattern of left ventricular geometry in hypertension: a study of a ...

    African Journals Online (AJOL)

    Background: Hypertension is a leading cause of cardioxasular morbidity and mortality in Nigeria. The main aim of this study was to deterine the prevalence of left ventricular hypertrophy and left ventricular geometric patterns among hypertensives in Kano, Nigeria. Methods: The study was cross-sectional in design, and ...

  16. Left Ventricular Non-Compaction Associated with WPW Syndrome

    Directory of Open Access Journals (Sweden)

    ParidokhtNakhostin Davari

    2006-07-01

    Full Text Available Noncompaction of the ventricular myocardium is an embryonic cardiomyopathy that is increasingly being recognized. Noncompaction of LV myocardium, right ventricular myocardium, or both can occur in isolation, in congenital heart diseases, in valvular heart diseases, in neuromuscular disorders, skeletal abnormalities and in endocrinologic abnormalities. Clinical manifestations of ventricular non-compaction include congestive heart failure, arrhythmia, sudden cardiac death and embolic events. This report is illustrative of non-compaction left ventricle associated with WPW syndrome in a 12-year-old girl presented with aborted sudden cardiac death and heart failure.

  17. Kronisk iskaemisk hjerteinsufficiens. Revaskularisering bedrer overlevelsen blandt patienter med hibernating myocardium

    DEFF Research Database (Denmark)

    Holdgaard, Paw Chr; Nielsen, Søren Steen; Wiggers, Henrik

    2007-01-01

    INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional myocardium (Hibernating myocardium, HIB) can benefit from revascularization. These patients can be selected with nuclear methods. The purpose of this study was to describe the results of the imaging procedures...

  18. Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium.

    Science.gov (United States)

    Kim, Paul J; Mahmoudi, Morteza; Ge, Xiaohu; Matsuura, Yuka; Toma, Ildiko; Metzler, Scott; Kooreman, Nigel G; Ramunas, John; Holbrook, Colin; McConnell, Michael V; Blau, Helen; Harnish, Phillip; Rulifson, Eric; Yang, Phillip C

    2015-03-27

    The mechanism of functional restoration by stem cell therapy remains poorly understood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta-derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and precardiac properties. In this study, the restorative effects of 3 AMC-derived subpopulations were examined in a murine myocardial injury model: (1) unselected AMCs, (2) ckit(+)AMCs, and (3) AMC-derived induced pluripotent stem cells (MiPSCs). To determine the differential restorative effects of the AMC-derived subpopulations in the murine myocardial injury model using multimodality imaging. SCID (severe combined immunodeficiency) mice underwent left anterior descending artery ligation and were divided into 4 treatment arms: (1) normal saline control (n=14), (2) unselected AMCs (n=10), (3) ckit(+)AMCs (n=13), and (4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular function, whereas bioluminescence imaging assessed stem cell engraftment during a 4-week period. Immunohistological labeling and reverse transcriptase polymerase chain reaction of the explanted myocardium were performed. The unselected AMC and ckit(+)AMC-treated mice demonstrated transient left ventricular functional improvement. However, the MiPSCs exhibited a significantly greater increase in left ventricular function compared with all the other groups during the entire 4-week period. Left ventricular functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSC-treated animals lacked any evidence of de novo cardiac differentiation. The functional restoration seen in MiPSCs was characterized by increased myocardial viability and sustained engraftment without de novo cardiac differentiation, indicating salvage of the injured myocardium. © 2015 American Heart Association, Inc.

  19. Miocárdio hibernante: uma realidade clínica Hibernant myocardium: a clinical reality

    Directory of Open Access Journals (Sweden)

    J.A. Marin-Neto

    1997-12-01

    Full Text Available O conceito da hibernação miocárdica implica a ocorrência de disfunção ventricular crônica, potencialmente reversível, causada por dissinergia regional, dependente de isquemia prolongada. Não tem fisiopatologia elucidada, em parte porque não existem modelos experimentais satisfatórios para seu estudo. Diversos métodos são capazes de demonstrar viabilidade miocárdica nas regiões que não exibem capacidade contrátil basal. O desmascaramento da hibernação nesses territórios pode ser feito mediante demonstração de reserva contrátil, de funcionamento normal da membrana celular, ou de metabolismo preservado. A correta identificação de miocárdio hibernante reveste-se de especial significado clínico, por suas implicações prognósticas quanto a intervenções de revascularização miocárdica, destinadas a reabilitar a função ventricular em muitos pacientes coronariopatas crônicos.Myocardial hibernation is believed to occur in ventricular dyssynergic regions chronically deprived of coronary flow enough to warrant the preservation of contractile function. Pathophysiology of this condition remains largely unclear, mainly because good experimental models for its study are still lacking. Various methods can be clinically employed to detect hibernation in patients with chronic ventricular dysfunction. These methods use the principle of unmasking contractile reserve, or are based on the demonstration of preserved membrane function or myocardium metabolism in the dyssynergic regions. The correct identification of viable hibernating myocardium is crucial in the process of deciding which coronary disease patients would potentially benefit from revascularization procedures.

  20. Proposed mechanism(s) of transitory ischemic injury to myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D.; Kelman, B.J.

    1979-01-01

    The main objective of this study was to produce primary acute ischemic injury to myocardium in a live animal. In vitro, guinea pig platelets were sensitive to perturbation and aggregation by a suspension of ultrafine fibrillary collagen material isolated from the aorta of an aged burro (Equus asinus). The platelets responded to this material down to 100 to 200 ng (dry weight) added to 0.45 ml of platelet-rich plasma, as determined by aggregometric technique. Aortic fibrillary collagen material injected IV into guinea pigs circulating platelets within 5 minutes. In blood samples taken 2.5 hours after injection, 50 to 75% of control levels of platelets were found. In other experiments, 3 anesthetized animals were injected by jugular vein with active fibrillary collagen material. Two control animals were injected with the same dose of the material that had been inactivated (15 minutes at 100 C). Intraventricular pressures and electrocardiographs (ECG) were monitored continuously for the first 30 minutes. The injection of the active fibrillary collagen material caused a large ventricular pressure elevation in approximately 40 s. Within 60 s, there was a reduction in the absolute platelet number in the peripheral circulation. The elevation of ventricular pressure persisted for approximately 5 minutes and was followed within 30 minutes by a set of ECG events suggestive of acute myocardial ischemic injury. The ECG changes seemed to be subsequent to platelet microthrombus formation in the pulmonary arterial microcirculation. By 2.5 hours after the treatment, platelets rebounded into the circulation in 2 surviving guinea pigs, and left ventricular pressures and ECG profiles returned to the preinfusion base lines. Guinea pigs IV infused with similar amounts of inactivated fibrillary collagen material did not show changes.

  1. Quantification of Shear Deformations and Corresponding Stresses in the Biaxially Tested Human Myocardium.

    Science.gov (United States)

    Sommer, Gerhard; Haspinger, Daniel Ch; Andrä, Michaela; Sacherer, Michael; Viertler, Christian; Regitnig, Peter; Holzapfel, Gerhard A

    2015-10-01

    One goal of cardiac research is to perform numerical simulations to describe/reproduce the mechanoelectrical function of the human myocardium in health and disease. Such simulations are based on a complex combination of mathematical models describing the passive mechanical behavior of the myocardium and its electrophysiology, i.e., the activation of cardiac muscle cells. The problem in developing adequate constitutive models is the shortage of experimental data suitable for detailed parameter estimation in specific functional forms. A combination of shear and biaxial extension tests with different loading protocols on different specimen orientations is necessary to capture adequately the direction-dependent (orthotropic) response of the myocardium. In most experimental animal studies, where planar biaxial extension tests on the myocardium have been conducted, the generated shear stresses were neither considered nor discussed. Hence, in this study a method is presented which allows the quantification of shear deformations and related stresses. It demonstrates an approach for experimenters as to how the generation of these shear stresses can be minimized during mechanical testing. Experimental results on 14 passive human myocardial specimens, obtained from nine human hearts, show the efficiency of this newly developed method. Moreover, the influence of the clamping technique of the specimen, i.e., the load transmission between the testing device and the tissue, on the stress response is determined by testing an isotropic material (Latex). We identified that the force transmission between the testing device and the specimen by means of hooks and cords does not influence the performed experiments. We further showed that in-plane shear stresses definitely exist in biaxially tested human ventricular myocardium, but can be reduced to a minimum by preparing the specimens in an appropriate manner. Moreover, we showed whether shear stresses can be neglected when performing

  2. Diagnosis of Non-compacted Myocardium of the Left Ventricle in Children

    Directory of Open Access Journals (Sweden)

    I.B. Yershova

    2014-05-01

    Full Text Available The authors presented a review of published literature data on rare congenital abnormalities in children — a non-compacted myocardium of the left ventricle, which refers to unclassified cardiomyopathy. This pathology by the American Heart Association classification relates to genetic cardiomyopathy. Non-compacted myocardium of the left ventricle in children develops due to violation of myocardial induration of the fetus in utero. Diagnosis of the disease is difficult due to the lack of specific clinical signs. The authors also presented a clinical case of non-compacted left ventricular myocardium in 6-year-old girl.

  3. Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study)

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva

    2010-01-01

    associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure...... was strongly associated with a reduced risk for hospitalization for heart failure.......Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension...

  4. [Ventricular pump function under ectopic excitation of the frog heart].

    Science.gov (United States)

    Kibler, N A; Belogolova, A S; Vaĭkshnoraĭte, M A; Azarov, Ia E; Shmakov, D N

    2008-02-01

    The ventricular pump function under ectopic excitation of the heart was studied in decapitated and pithed adult frogs Rana temporaria (n = 21) at 18-19 degrees C. The intraventricular pressure was recorded with a catheter via ventricular wall. During pacing of the ventricular base and apex, the systolic pressure decreased (6.1 +/- 4.5 mm Hg and 8.9 +/- 5.0 mm Hg, respectively) as compared to the supraventricular rhythm (8.9 +/- 5.0 mm Hg, p < 0.05). The end-diastolic pressure decreased insignificantly both under basal and apical pacing. The systolic rate of pressure rise during dP/dtmax decreased under ventricular pacing, especially during pacing of the ventricular apex, as compared to the supraventricular rhythm (14.4 +/- 6/9 mm Hg/s and 22.1 +/- 11.2 mm Hg/s, respectively, p < 0.003). The isovolumetric relaxation (dP/dtmin) slowed during apical pacing as compared to the supraventricular rhythm (-25.1 +/- 13.6 and -35.6 +/- 18.3 mm Hg/s, respectively, p < 0.03). Ectopic excitation of the ventricular base and apex resulted in increase of the QRS duration (93 +/- 33 ms and 81 +/- 30 ms, respectively) as compared to the supraventricular rhythm (63 +/- 13 ms, p < 0.05). Thus, pacing of different ventricular areas ventricular myocardium with the ventricular pump function being reduced more obviously during the apical pacing compared to the pacing of ventricular base.

  5. Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

    Science.gov (United States)

    Rischpler, Christoph; Dirschinger, Ralf J; Nekolla, Stephan G; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

    2016-04-01

    The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, Pfunctional outcome independent of infarct size (Δ ejection fraction: Pfunctional outcome at 6 months. Thus, (18)F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. © 2016 American Heart Association, Inc.

  6. External ventricular drain causes brain tissue damage: an imaging study.

    Science.gov (United States)

    Ortolano, Fabrizio; Carbonara, Marco; Stanco, Antonella; Civelli, Vittorio; Carrabba, Giorgio; Zoerle, Tommaso; Stocchetti, Nino

    2017-10-01

    An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions. Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes. In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time. EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema.

  7. Remodeling of the myocardium in early trabeculation and cardiac valve formation; a role for TGFβ2.

    Science.gov (United States)

    Kruithof, Boudewijn P T; Kruithof-De-Julio, Marianna; Poelmann, Robert E; Gittenberger-De-Groot, Adriana C; Gaussin, Vinciane; Goumans, Marie-José

    2013-01-01

    Trabeculation and the formation of the leaflets of the mitral and tricuspid valves both involve remodeling of the embryonic myocardium. The nature and possible connection of these myocardial remodeling processes, however, are unclear. Therefore, we examined the morphogenesis of the early ventricular and atrioventricular (AV) myocardium and report for the first time that the formation of the early trabeculae and the positioning of the valve primordia (endocardial cushions) into the ventricular lumen are part of one continuous myocardial remodeling process, which involves the dissociation of the myocardial layers. For the endocardial cushions, this process results in delamination from the AV myocardium. The AV myocardium that will harbor the right lateral cushion is the exception and becomes positioned in the ventricular lumen by folding of the right ventricle. As a consequence, remodeling of the left and right AV myocardium occurs differently with implications for the formation of the mural leaflets and annulus fibrosis. At both the right and left side, the valvular myocardium harbors a distinct molecular phenotype and its removal from the cardiac leaflets involves a second wave of delamination. Interestingly, in the TGFβ2-KO mouse, which is a known model for cushion and valve defects, remodeling of the early myocardium is disturbed as indicated by defective trabeculae formation, persistence of valvular myocardium, disturbed myocardial phenotypes and differential defects at left and right side of the AV canal. Based on these results we propose a new model clarifying early trabeculae formation and AV valve formation and provide new inroads for an enhanced understanding of congenital heart defects.

  8. Hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-11-01

    Full Text Available A case report of apical left ventricular aneurysm in patient with hypertrophic cardiomyopathy with mid-ventricular obstruction (diagnosis and surgical treatment is presented. We revealed apical aneurysm and mid-ventricular obstruction during echocardiography and specified anatomical characteristics of aneurysm during computer tomography. There was no evidence of obstructive coronary artery disease during coronary angiography. Taking into consideration multiple cerebral infarcts, aneurysm resection and left ventricular plastics was performed. Electronic microscopy of myocardium confirmed the diagnosis of hypertrophic cardiomyopathy.

  9. An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle.

    Science.gov (United States)

    Hassaballah, Abdallah I; Hassan, Mohsen A; Mardi, Azizi N; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium's tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle.

  10. An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle.

    Directory of Open Access Journals (Sweden)

    Abdallah I Hassaballah

    Full Text Available The determination of the myocardium's tissue properties is important in constructing functional finite element (FE models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility, as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle.

  11. OCT imaging of myocardium extending to pulmonary vein

    Science.gov (United States)

    Li, Zhifang; Dickfeld, Timm; Tang, Qinggong; Wang, Bohan; Chen, Yu

    2016-02-01

    In this study, we propose to use optical coherence tomography to enable a direct visualization of myocardium extending into the pulmonary vein (PV). The results showed that there are obvious differences in the morphology of myocardium and fibrous tissue in the transition region of myocardial sleeve, which is in agreement with the histological analysis. In addition, the myocardial area in transition point has three layers in the depth of 1 mm, and the depth-resolved myocardial fiber show different orientation in the different layers. This characteristic was applied for segmentation of the structures of myocardium extending into PV.

  12. Applications of magnetic resonance imaging in the assessment of left ventricular dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Beacock, David John

    2002-07-01

    This thesis has described the use of Magnetic Resonance Imaging (MRI) in the investigation of left ventricular dimensions and systolic function. This has been performed in conditions of left ventricular dysfunction, in congestive cardiac failure and following anterior myocardial infarction. The reproducibility of measurements of left ventricular dimensions using MRI has been presented. Such measurements were shown to be reproducible between different MRI studies of normal volunteers and patients with congestive heart failure. Furthermore, measurements from different MRI studies obtained from two commercially different systems were reproducible for the same subject groups. Ventricular dimensions and systolic function was evaluated in adult normal volunteers of different ages. Although left ventricular volumes and mass remained unchanged, detailed studies of the systolic images revealed significant differences between the two age groups. Differences in left ventricular cavity volumes and mass between patients with congestive heart failure and age-matched normal volunteers were also investigated. Left ventricular volumes and myocardial mass were assessed in a group of patients following anterior myocardial infarction. End-systolic volume was significantly increased compared to age-matched volunteers, but no changes in end-diastolic volume or myocardial mass was observed. Serial re-evaluation of these patients revealed no other changes over the subsequent six months. All these patients were treated with optimal medical therapy (thrombolysis, aspirin, beta-blockade and angiotensin converting enzyme inhibition). Thus, the use of this therapy may attenuate the process of left ventricular remodelling. Regional wall thickness was measured in the post-infarct patients. Wall thickening was significantly reduced both in the infarcted regions and in myocardium remote to the infarction. In contrast to previous echocardiographic studies, no 'hypercontractility' was

  13. Ventricular arrhythmias in patients with newly diagnosed nonischemic cardiomyopathy: Insights from the PROLONG study.

    Science.gov (United States)

    Duncker, David; König, Thorben; Hohmann, Stephan; Bauersachs, Johann; Veltmann, Christian

    2017-08-01

    Patients with nonischemic cardiomyopathy (NICM) reportedly have low incidence of appropriate shocks from wearable cardioverter-defibrillators (WCDs). A recent study questions the benefit from primary preventive implantation of implantable cardioverter-defibrillators in NICM. We therefore analyzed a subgroup of patients with NICM from the PROLONG study. Patients with newly diagnosed NICM show a risk for ventricular tachyarrhythmia. The PROLONG study included 167 patients with newly diagnosed heart failure and left ventricular ejection fraction (LVEF) ≤35% with a WCD. Patients with NICM were identified and included in this analysis. 117 patients presented with NICM. Sixty-five (55%) were male; mean age was 51 ± 15 years. Mean LVEF at diagnosis was 23% ± 7%. Mean follow-up was 11 ± 10 months. Mean WCD wear time was 101 ± 82 days; mean wear time per day was 21.4 ± 4.5 hours. Overall, 12 ventricular arrhythmias occurred in 10 (9%) patients (6 DCM, 4 PPCM). Nine appropriate WCD shocks for hemodynamically unstable ventricular tachycardia/fibrillation in 8 (7%) patients were observed. Two patients presented sustained hemodynamically stable ventricular tachycardia for >30 minutes detected by the WCD, but withheld WCD therapy. Patients with newly diagnosed NICM and LVEF ≤35% show an elevated risk of ventricular tachycardia/fibrillation during initiation and optimization of heart failure therapy. To prevent sudden cardiac death, WCD should be considered in patients with newly diagnosed NICM with severely reduced LVEF. © 2017 Wiley Periodicals, Inc.

  14. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  15. MRI assessment of right ventricular dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Di Cesare, Ernesto [Department of Radiology, University of L' Aquila, via Vetoio 1, 67100, L' Aquila (Italy)

    2003-06-01

    Right ventricular dysplasia is a new entity of unknown origin in the classification of cardiomyopathies. Also known as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia, it is a disease of the heart muscle characterised by fibroadipose atrophy mainly involving the right ventricle and responsible for severe ventricular arrhythmias and sudden death also in young people. Magnetic resonance imaging provides evidence of ventricular dilatation at the outflow tract, thinning and thickening of the wall, diastolic bulging areas (especially located at the level of the right ventricle outflow tract) and fatty substitution of the myocardium mainly at the level of the right ventricle. Many radiologists erroneously consider the previously described fatty substitution as the main sign of ARVC, even though an evaluation of fat substitution alone may be a source of error for two reasons: firstly, because isolated areas of fatty replacement are not synonymous with ARVC since small non-transmural focal fatty areas of fat are also present in the normal patients; and secondly, because the MRI detection of fat may be overestimated due to partial-volume artefacts with normal subepicardial fat. Cardiac MRI can also be employed for the diagnosis of idiopathic right ventricular outflow tract tachycardia. Considering the evolutive nature of the disease, the non-invasiveness of MRI allows the follow-up of these patients and may be considered an excellent screening modality for the diagnosis of ARVC in family members. Finally, MRI can be employed in electrophysiological studies to locate the arrhythmogenic focus and reduce sampling errors. (orig.)

  16. Vegfa Impacts Early Myocardium Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Diqi Zhu

    2017-02-01

    Full Text Available Vascular endothelial growth factor A (Vegfa signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk.

  17. Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations.

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    Full Text Available Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h, as ventricular couplets (Couplet, or as non-sustained ventricular tachycardia (nsVT, and during 31±18 months of follow-up as ventricular tachycardia (VT events (VTE such as sudden cardiac death (SCD, and sustained ventricular tachycardia (sVT. We identified >10 PVC/h in 28 (35%, Couplet/nsVT in 32 (40%, and VTE in 6 patients (8%, including 3 with SCD (4%. PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020, to moderate mitral valve regurgitation (P = .018 and P = .003, and to prolonged QTc intervals (P = .001 and P = .006, respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021. Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001 and with mutations in exons 24-32 (P<.001.Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

  18. Synergic effects of renin and aldosterone on right ventricular function in hypertension: a tissue Doppler study.

    Science.gov (United States)

    Gregori, Mario; Giammarioli, Benedetta; Tocci, Giuliano; Befani, Alberto; Ciavarella, Giuseppino Massimo; Ferrucci, Andrea; Paneni, Francesco

    2015-12-01

    Right ventricular dysfunction (RVD) is associated with poor cardiovascular outcome. The renin-angiotensin-aldosterone system is involved in alterations of the left ventricular geometry and function. Detrimental effects of the renin-angiotensin-aldosterone system on the right ventricular function are being postulated, but data supporting this assumption are still lacking. The aim of the study was to assess the impact of hyperreninemia, hyperaldosteronism or their combination on right ventricular function in hypertensive individuals. Plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) were measured in 116 hypertensive patients, divided as follows: normal PRA and PAC (n = 38); high PRA and normal PAC (hypereninemia) (n = 26); normal PRA and high PAC (hyperaldosternism) (n = 27); high PRA and PAC (HRA) (n = 25). Echocardiographic evaluation of the left and right ventricles (RV), including tissue Doppler imaging, was performed. RVD was identified by tissue Doppler Imaging-derived Myocardial Performance Index, calculated with a multisegmental approach. Indices of the right ventricular structure and function, as well as the prevalence of RVD, were higher in hyperreninemia and hyperaldosternism groups as compared with the normal group, and a further increase was observed in the HRA patients. Regression models showed a similar risk of RVD in the hyperreninemia and hyperaldosternism patients, regardless of systemic and pulmonary pressure, as well as left ventricular dysfunction. Notably, patients with both hyperreninemia and hyperaldosternism exhibited the strongest association with RVD as compared with patients with only hyperreninemia or hyperaldosternism. Isolated hyperreninemia or hyperaldosternism determines a similar impairment of the right ventricular function, whereas their combination is further detrimental. Renin and aldosterone may represent early biomarkers of right ventricular dysfunction in hypertension.

  19. Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study)

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva

    2010-01-01

    valve flow pattern, this was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial diameter, LV mass index, and treatment in time-varying Cox analyses. In contrast, lower in-treatment E/A ratios and shorter mitral valve deceleration times were...... associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure......Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension...

  20. Collagen XIV is important for growth and structural integrity of the myocardium

    Science.gov (United States)

    Tao, Ge; Levay, Agata K.; Peacock, Jacqueline D.; Huk, Danielle J.; Both, Sarah N.; Purcell, Nicole H.; Pinto, Jose R.; Galantowicz, Maarten L.; Koch, Manuel; Lucchesi, Pamela A.; Birk, David E.; Lincoln, Joy

    2012-01-01

    Collagen XIV is a fibril-associated collagen with an interrupted triple helix (FACIT). Previous studies have shown that this collagen type regulates early stages of fibrillogenesis in connective tissues of high mechanical demand. Mice null for Collagen XIV are viable, however formation of the interstitial collagen network is defective in tendons and skin leading to reduced biomechanical function. The assembly of a tightly regulated collagen network is also required in the heart, not only for structural support but also for controlling cellular processes. Collagen XIV is highly expressed in the embryonic heart, notably within the cardiac interstitium of the developing myocardium, however its role has not been elucidated. To test this, we examined cardiac phenotypes in embryonic and adult mice devoid of Collagen XIV. From as early as E11.5, Col14a1−/− mice exhibit significant perturbations in mRNA levels of many other collagen types and remodeling enzymes (MMPs, TIMPs) within the ventricular myocardium. By post natal stages, collagen fibril organization is in disarray and the adult heart displays defects in ventricular morphogenesis. In addition to the extracellular matrix, Col14a1−/− mice exhibit increased cardiomyocyte proliferation at post natal, but not E11.5 stages, leading to increased cell number, yet cell size is decreased by 3 months of age. In contrast to myocytes, the number of cardiac fibroblasts is reduced after birth associated with increased apoptosis. As a result of these molecular and cellular changes during embryonic development and post natal maturation, cardiac function is diminished in Col14a1−/− mice from 3 months of age; associated with dilation in the absence of hypertrophy, and reduced ejection fraction. Further, Col14a1 deficiency leads to a greater increase in left ventricular wall thickening in response to pathological pressure overload compared to wild type animals. Collectively, these studies identify a new role for type XIV

  1. Histology and Immunohistochemistry of the Cardiac Ventricular Structure in the Green Turtle (Chelonia mydas).

    Science.gov (United States)

    Braz, J K F S; Freitas, M L; Magalhães, M S; Oliveira, M F; Costa, M S M O; Resende, N S; Clebis, N K; Silva, N B; Moura, C E B

    2016-08-01

    This study describes the implications of cardiac ventricular microscopy in Chelonia mydas relating to its ability to dive. For this work, 11 specimens of the marine turtle species C. mydas found dead on the coast of Rio Grande do Norte (Northeast Brazil) were used. After necropsy, fragments of the cardiac ventricular wall were fixed in 10% buffered formaldehyde solution for 24 h and then subjected to routine processing for light and scanning electron microscopy (SEM). The ventricle in this species is formed by the epicardium, myocardium and endocardium. The subepicardial layer consists of highly vascularised connective tissue that emits septa to reinforce the myocardium surface. There is an abundant and diffuse subepicardial nerve plexus shown by immunostaining technique. The thickness of the spongy myocardium and the nature of its trabeculae varied between the heart chambers. The endocardium shows no characteristic elements of the heart conduction system. The valves have a hyaline cartilage skeleton, coated by dense irregular connective tissues characterised by elastic fibres. These findings in the green turtle ventricular microscopy are related to hypoxia resistance during diving. © 2015 Blackwell Verlag GmbH.

  2. Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Wiggers, Henrik; Bøtker, Hans Erik

    2009-01-01

    Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM).......Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM)....

  3. Effect of Commiphora mukul extract on cardiac dysfunction and ventricular function in isoproterenol-induced myocardial infarction.

    Science.gov (United States)

    Ojha, Shreesh K; Nandave, Mukesh; Arora, Sachin; Mehra, Raj D; Joshi, Sujata; Narang, Rajiv; Arya, D S

    2008-09-01

    In present study, hydroalcoholic extract of C. mukul significantly improved the cardiac function and prevented myocardial ischemic impairment manifested in the form of increased heart rate, decreased arterial pressure, increased left ventricular end diastolic pressure, and altered myocardial contractility indices. C. mukul treatment additionally also produced a significant increase in lactate dehydrogenase levels and prevented decline of protein content in heart. C. mukul preserved the structural integrity of myocardium. Reduced leakage of myocyte enzyme lactate dehydrogenase and maintenance of structural integrity of myocardium along with favorable modulation of cardiac function and improved cardiac performance indicate the salvage of myocardium with C. mukul treatment. Guggulsterones which are considered to be responsible for most of the therapeutic properties of C. mukul may underlie the observed cardioprotective effect of C. mukul against cardiac dysfunction in isoproterenol-induced ischemic rats.

  4. Effects of low-dose dobutamine on left ventricular function in normal subjects as assessed by gated single-photon emission tomography myocardial perfusion studies

    Energy Technology Data Exchange (ETDEWEB)

    Everaert, H.; Vanhove, C.; Franken, P.R. [Div. of Nuclear Medicine, University Hospital, Free University of Brussels (Belgium)

    1999-10-01

    Electrocardiography gated single-photon emission tomography (gated SPET) allows the assessment of regional perfusion and function simultaneously and in full spatial congruency. In this study changes in global and regional left ventricular function in response to dobutamine infusion were assessed in ten healthy volunteers using sequential gated SPET myocardial perfusion acquisitions. Four consecutive gated SPET images were recorded 60 min after injection of 925 MBq technetium-99m tetrofosmin on a three-head camera equipped with focussing collimators. Two acquisitions were made at rest (baseline 1 and 2), and the third and fourth acquisitions were started 5 min after the beginning of the infusion of 5 and 10 {mu}g kg{sup -1} min{sup -1} dobutamine, respectively. Systolic wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) and volumes were calculated automatically using the Cedars-Sinai program. Nine of the ten subjects presented a definite increase in WT during dobutamine infusion. WT increased on average from 46%{+-}14% at baseline to 71%{+-}23% (range: 37%-106%; P<0.05) during 5 {mu}g kg{sup -1} min{sup -1} dobutamine infusion and to 85%{+-}25% (range: 62%-123%; P<0.05 with respect to WT at 5 {mu}g kg{sup -1} min{sup -1}) during 10 {mu}g kg{sup -1} min{sup -1} dobutamine infusion. Apical segments showed the largest WT at baseline. The average WT response to dobutamine was similar for all parts of the myocardium. It is concluded that changes in WT induced by infusion of low-dose dobutamine can be assessed by sequential gated SPET myocardial perfusion studies. The ''stress gated SPET'' protocol proposed in this study might be helpful to distinguish viable from scar tissue in patients with coronary artery disease, by demonstrating a preserved inotropic response in hypoperfused myocardium. (orig.)

  5. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents.

    Science.gov (United States)

    Liu, Alexander; Wijesurendra, Rohan S; Francis, Jane M; Robson, Matthew D; Neubauer, Stefan; Piechnik, Stefan K; Ferreira, Vanessa M

    2016-01-01

    The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 ± 84 ms), without significant T1 reactivity (0.2 ± 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p T1 reactivity (0.2 ± 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 ± 17 ms; p = 0.92), showed blunted T1 reactivity (3.9 ± 0.6%; p T1 mapping at rest and

  6. Myocardial strain in sub-acute peri-infarct myocardium.

    Science.gov (United States)

    Ruzsics, Balázs; Surányi, Pál; Kiss, Pál; Brott, Brigitta C; Litovsky, Silvio; Denney, Thomas S; Aban, Inmaculada; Lloyd, Steven G; Simor, Tamas; Elgavish, Gabriel A; Gupta, Himanshu

    2009-02-01

    In the absence of additional ischemic insults, the peri-infarct region surrounding the infarct myocardium can recover function. T2 weighted MRI signal is sensitive to edema and used to detect peri-infarct, salvageable myocardium. The main purpose of this study was to investigate the alterations in myocardial strain in the peri-infarct myocardium as compared to normal and infarct myocardium. Comprehensive MRI of the myocardium was performed in five pigs 6-7 days following coronary artery occlusion-reperfusion myocardial injury. MRI included tagged cine images for myocardial strain, T2weighted (T2w)-images and late gadolinium enhancement (LGE) for assessing myocardial viability. Automated signal intensity thresholds were used to define tissue edema and myocardial infarct. Maximum-shortening strains were analyzed in the infarct, peri-infarct and normal myocardial sectors. The results were correlated with triphenyltetrazolium-chloride (TTC) and hemotoxylin-eosin stained tissue images. We found an excellent correlation of LGE with TTC (r = 0.94, P myocardial sectors had higher myocardial strain than infarct myocardial sectors (P myocardial strain measurements provide complementary information and both may be useful for characterization of the peri-infarct myocardium.

  7. A mismatch index based on the difference between measured left ventricular ejection fraction and that estimated by infarct size at three months following reperfused acute myocardial infarction

    DEFF Research Database (Denmark)

    Carlsen, Esben A; Bang, Lia E; Lønborg, Jacob

    2014-01-01

    BACKGROUND AND AIM: The reduction of left ventricular ejection fraction (LVEF) following ST-segment elevation myocardial infarction (STEMI) is a result of infarcted myocardium and may involve dysfunctional but viable myocardium. An index that may quantitatively determine whether LVEF is reduced...... beyond the expected value when considering only infarct size (IS) has previously been presented based on cardiac magnetic resonance (CMR). The purpose of this study was to introduce the index based on the electrocardiogram (ECG) and compare indices based on ECG and CMR. METHOD AND RESULTS: In 55 patients...

  8. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

    Science.gov (United States)

    Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

    2017-09-07

    Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

  9. Assessment of muscular ventricular septal defect closure by transcatheter or surgical approach: a three-dimensional echocardiographic study.

    Science.gov (United States)

    Acar, P; Abdel-Massih, T; Douste-Blazy, M-Y; Dulac, Y; Bonhoeffer, P; Sidi, D

    2002-09-01

    Previous classification of muscular ventricular septal defects (VSDs) visualized on two-dimensional echocardiography relied on artificial divisions of the septum. New visualization of the ventricular septum integrating the third dimension would facilitate communication between cardiologists and surgeons. The objectives of this study were (1) to assess in patients with muscular ventricular septal defects the accuracy of left ventricular three-dimensional echocardiographic reconstructions in demonstrating the position, the size and the tissue rims of the defects; (2) to compare findings by three-dimensional echocardiography with those obtained by surgical and transcatheter approaches. Twenty-six patients, aged from one month to 40 years, with muscular ventricular septal defects underwent three-dimensional echocardiographic study. From the left ventricular three-dimensional echocardiographic reconstructions, the localization, the maximal diameter and the tissue rim of the defect were analysed and compared with surgical or transcatheter findings. Optimal three-dimensional echocardiographic reconstructions were obtained in 22 patients. Nineteen had a single muscular ventricular septal defect and three had multiple muscular ventricular septal defects. The muscular ventricular septal defect localizations were the inlet septum in three, the outlet septum in three, the mid-muscular septum in 14 and the apex in eighth. In 10 patients who underwent surgical closure, the correlation between three-dimensional echocardiography and surgery for muscular ventricular septal defect maximal diameter was y=0 x 95 x +0.13 (r=0.98; Pventricular septal defect localization were complete. In five patients who underwent transcatheter closure, the mean difference between three-dimensional echocardiographic maximal diameter and stretched diameter was 1 x 8+/-0 x 5 mm. The three-dimensional echocardiographic left ventricular views provide a new and easily communicated visualization of various

  10. Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury.

    Science.gov (United States)

    Ojha, Shreesh Kumar; Sharma, Charu; Golechha, Mahaveer Jain; Bhatia, Jagriti; Kumari, Santosh; Arya, Dharamvir Singh

    2015-02-01

    The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity. © The Author(s) 2012.

  11. Body mass index and myocardium at risk in patients with acute coronary syndrome.

    Science.gov (United States)

    Arrebola-Moreno, A L; Marfil-Alvarez, R; Catena, A; García-Retamero, R; Arrebola, J P; Melgares-Moreno, R; Ramirez-Hernández, J A; Kaski, J C

    2014-04-01

    Whilst traditional studies have shown that obese individuals are at a higher risk of cardiovascular events compared to lean subjects, recent studies in patients with acute myocardial infarction (AMI) have suggested that obesity may exert protective effects (the "obesity paradox"). We sought to assess the relationship between body mass index (BMI) and the BARI score (BARIsc), a validated tool used to assess myocardium at risk, in patients with acute coronary syndrome. Participants were 116 consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI). Demographics, BMI, risk factors, biochemistry data, left ventricular function, angiographic data and the BARIsc were assessed in every patient. Multiple linear regression analyses showed that BMI significantly correlated with BARIsc; β=.23, p<0.02. This was found only in the overweight/obese patients, β=.27, p<0.01, but not in patients with normal BMIs, β=0.08, p=0.71. An increased body weight is associated with an increased area of myocardium at risk in patients with ACS. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Depressed recovery of subendocardial perfusion in persistent heart failure after complete revascularisation in diabetic patients with hibernating myocardium.

    Science.gov (United States)

    Mizuno, R; Fujimoto, S; Saito, Y; Nakamura, S

    2009-05-01

    To investigate the relation between myocardial perfusion and heart failure (HF) status after revascularisation in patients with HF due to hibernating myocardium (HM) in diabetic and non-diabetic subjects. 31 diabetic and 33 non-diabetic subjects with HF due to HM, who were already scheduled for complete revascularisation, were studied. Before and after revascularisation, left ventricular function and regional perfusion in subendocardial and subepicardial portions of the left ventricular wall were evaluated. Before revascularisation, left ventricular function and regional perfusion were similar in diabetic and non-diabetic subjects. At 6 months after revascularisation, subepicardial perfusion was markedly improved both in diabetic and non-diabetic subjects. However, subendocardial perfusion was markedly improved only in non-diabetic subjects and was little changed in diabetic patients. Thus, subendocardial perfusion was much lower in diabetic than non-diabetic subjects. Left ventricular function was improved more in non-diabetic than in diabetic subjects. Persistent HF was found much more often in diabetic than non-diabetic subjects. At multivariate analysis, subendocardial perfusion at 6 months independently contributed to persistent HF. This study describes the intramural heterogeneity of recovery of myocardial perfusion with depressed improvement in the subendocardial portion and its relation with persistent HF after complete revascularisation in diabetic patients with HF due to HM.

  13. Mild hypothermia delays the development of stone heart from untreated sustained ventricular fibrillation--a cardiovascular magnetic resonance study.

    Science.gov (United States)

    Sorrell, Vincent L; Paleru, Vijayasree; Altbach, Maria I; Hilwig, Ronald W; Kern, Karl B; Gaballa, Mohamed; Ewy, Gordon A; Berg, Robert A

    2011-03-06

    'Stone heart' resulting from ischemic contracture of the myocardium, precludes successful resuscitation from ventricular fibrillation (VF). We hypothesized that mild hypothermia might slow the progression to stone heart. Fourteen swine (27 ± 1 kg) were randomized to normothermia (group I; n=6) or hypothermia groups (group II; n=8). Mild hypothermia (34 ± 2 °C) was induced with ice packs prior to VF induction. The LV and right ventricular (RV) cross-sectional areas were followed by cardiovascular magnetic resonance until the development of stone heart. A commercial 1.5T GE Signa NV-CV/i scanner was used. Complete anatomic coverage of the heart was acquired using a steady-state free precession (SSFP) pulse sequence gated at baseline prior to VF onset. Un-gated SSFP images were obtained serially after VF induction. The ventricular endocardium was manually traced and LV and RV volumes were calculated at each time point. In group I, the LV was dilated compared to baseline at 5 minutes after VF and this remained for 20 minutes. Stone heart, arbitrarily defined as LV volume model of prolonged untreated VF, hypothermia reduced the early LV dilatation and importantly, delayed the onset of stone heart thereby extending a known, morphologic limit of resuscitability. © 2011 Sorrell et al; licensee BioMed Central Ltd.

  14. Mild hypothermia delays the development of stone heart from untreated sustained ventricular fibrillation - a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Kern Karl B

    2011-03-01

    Full Text Available Abstract Background 'Stone heart' resulting from ischemic contracture of the myocardium, precludes successful resuscitation from ventricular fibrillation (VF. We hypothesized that mild hypothermia might slow the progression to stone heart. Methods Fourteen swine (27 ± 1 kg were randomized to normothermia (group I; n = 6 or hypothermia groups (group II; n = 8. Mild hypothermia (34 ± 2°C was induced with ice packs prior to VF induction. The LV and right ventricular (RV cross-sectional areas were followed by cardiovascular magnetic resonance until the development of stone heart. A commercial 1.5T GE Signa NV-CV/i scanner was used. Complete anatomic coverage of the heart was acquired using a steady-state free precession (SSFP pulse sequence gated at baseline prior to VF onset. Un-gated SSFP images were obtained serially after VF induction. The ventricular endocardium was manually traced and LV and RV volumes were calculated at each time point. Results In group I, the LV was dilated compared to baseline at 5 minutes after VF and this remained for 20 minutes. Stone heart, arbitrarily defined as LV volume Conclusions In this closed-chest swine model of prolonged untreated VF, hypothermia reduced the early LV dilatation and importantly, delayed the onset of stone heart thereby extending a known, morphologic limit of resuscitability.

  15. Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

    Science.gov (United States)

    Poyraz, Esra; Öz, Tuğba Kemaloğlu; Zeren, Gönül; Güvenç, Tolga Sinan; Dönmez, Cevdet; Can, Fatma; Güvenç, Rengin Çetin; Dayı, Şennur Ünal

    2017-09-01

    In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p risk for developing overt systolic dysfunction.

  16. Preliminary report of an ongoing phase I/II dose range, safety and efficacy study of iodine-123-phenylpentadecanoic acid for the identification of viable myocardium.

    Science.gov (United States)

    Hansen, C L

    1994-04-01

    An agent that can accurately and cost-effectively identify viable myocardium is needed to select the patients most likely to benefit from myocardial revascularization. Iodine-123-phenylpentadecanoic acid (IPPA) is a synthetic radiolabeled fatty acid that has shown promise in evaluating patients with coronary artery disease (CAD). IPPA has unique metabolic properties that may make it superior to other single-photon agents used for this task. A Phase I/II study is underway to evaluate safety, dose range and efficacy of IPPA in assessing viability and predicting functional recovery after revascularization. Patients between the ages of 21 and 75 with angiographically documented CAD, who were being referred for coronary revascularization, were recruited. The patients were randomized to receive 2, 4 or 6 mCi of IPPA and then underwent sequential SPECT imaging at 4, 12, 20, 28 and 36 min after injection. Radionuclide ventriculography and perfusion imaging were performed before and again 8 wk after revascularization. Myocardial metabolic activity of IPPA was analyzed and compared to the preinjection and postejection fractions. There were no significant adverse effects from the administration of IPPA. Image quality was dose-dependent; the 2-mCi dose was not consistently acceptable for quantitative analysis. These preliminary data show that IPPA is safe and can produce myocardial images of good quality when 4 mCi or more are used. Early results are encouraging but more experience will be needed to define the role of IPPA in identifying myocardial viability.

  17. Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

    Science.gov (United States)

    Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

    2012-12-01

    The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, Pmetabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, Pmetabolic acidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

  18. The endothelial nitric oxide synthase cofactor tetrahydrobiopterin shields the remote myocardium from apoptosis after experimental myocardial infarction in vivo.

    Science.gov (United States)

    Heidrich, Felix M; Jercke, Marcel C; Ritzkat, Anna; Ebner, Annette; Poitz, David M; Pfluecke, Christian; Quick, Silvio; Speiser, Uwe; Simonis, Gregor; Wäßnig, Nadine K; Strasser, Ruth H; Wiedemann, Stephan

    2017-08-23

    Following myocardial infarction (MI), apoptosis occurs early in the remote myocardium and contributes to the processes of myocardial remodeling. Increased nitrosative stress is a well-known and potent inductor of myocardial apoptosis. Excess activation of endothelial nitric oxide synthase (eNOS) increases its uncoupling potential and results in nitrosative stress via formation of peroxynitrite. However, the pathophysiologic role of eNOS signaling in the remote myocardium after MI is as yet undefined. The impact of eNOS activation on pro- and anti-apoptotic signaling in the remote myocardium and the influence of pretreatment with the eNOS cofactor tetrahydrobiopterin (BH4) on eNOS activation, nitrosative stress level and apoptosis induction and execution were studied in a rat myocardial infarction model in vivo. 24 hours after anterior MI, eNOS activity in animals treated with left anterior descending coronary artery ligation (LIG) significantly increased in the posterior left ventricular myocardium as did protein nitrosylation when compared to sham treatment. This was paralleled by induction of apoptosis via both, the extrinsic and intrinsic pathways. Moreover, anti-apoptotic signaling via protein kinase B/Akt and glycogen synthase-kinase 3 beta was suppressed. Notably, pretreatment with the eNOS cofactor BH4 reduced eNOS activation, prevented excess protein nitrosylation, blunted apoptosis induction, facilitated anti-apoptotic signaling and eventually prevented apoptosis execution. Here we showed that 24 hours after experimental MI in rats in vivo, apoptosis was induced in the posterior non-infarcted LV wall. Evidence is presented that pretreatment with the eNOS cofactor BH4 resulted in less nitrosative stress and weakened apoptotic processes, although stabilizers contained did participate in this phenomenon. Because apoptosis is a crucial component of myocardial remodeling, influencing eNOS signaling might be an interesting pharmacological target for the

  19. Arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Soni, Roopali; Oade, Yvette

    2011-08-24

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disease of the heart muscle that causes ventricular tachyarrhythmias and sudden death in young people and athletes. It results in fibrofatty replacement of the right ventricle, and the subepicardial region of the left ventricle. It is the most common cause of sudden cardiac death in young people after hypertrophic heart disease. Diagnosis can be difficult and at present there is no cure for ARVC. Prevention of sudden death is the most important management strategy. Paediatricians need to be aware of the possibility of ARVC in adolescents and young adults presenting with palpitations, fatigue, syncope or cardiac arrest. The authors present two cases of apparently healthy teenage boys who died suddenly and unexpectedly. Postmortem examination of the myocardium was strongly suggestive of ARVC in both cases.

  20. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Roberts, Jason D; Veinot, John P; Rutberg, Julie; Gollob, Michael H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Control of a Pediatric Pulsatile Ventricular Assist Device: A Hybrid Cardiovascular Model Study.

    Science.gov (United States)

    Ferrari, Gianfranco; Di Molfetta, Arianna; Zieliński, Krzysztof; Fresiello, Libera; Górczyńska, Krystyna; Pałko, Krzysztof Jakub; Darowski, Marek; Amodeo, Antonio; Kozarski, Maciej

    2017-12-01

    The aim of this work is to study pediatric pneumatic ventricle (PVAD) performance, versus VAD rate (VADR) and native heart rate (HR) ratio Rr (VADR/HR). The study uses a hybrid model of the cardiovascular system (HCS). HCS consists of a computational part (a lumped parameter model including left and right ventricles, systemic and pulmonary arterial and venous circulation) interfaced to a physical part. This permits the connection of a VAD (15 mL PVAD). Echocardiographic and hemodynamic data of a pediatric patient (average weight 14.3 kg, HR 100 bpm, systemic pressure 75/44 mm Hg, CO 1.5 L/min) assisted apically with asynchronous PVAD were used to set up a basal condition in the model. After model tuning, the assistance was started, setting VAD parameters (ejection and filling pressures, systole duration) to completely fill and empty the PVAD. The study was conducted with constant HR and variable VADR (50-120, step 10, bpm). Experiments were repeated for two additional patients' HRs, 90 and 110 bpm and for two values of systemic arterial resistance (Ras ) and Emax . Experimental data were collected and stored on disk. Analyzed data include average left and right ventricular volumes (LVV, RVV), left ventricular flow (LVF), VAD flow (VADF), and total cardiac output (COt). Data were analyzed versus Rr. LVV and RVV are sensitive to Rr and a left ventricular unloading corresponds in general to a right ventricular loading. In the case of asynchronous assistance, frequency beats are always present and the beat rate is equal to the difference between HR and VADR. In the case of pulsatile asynchronous LVAD assistance, VADR should be chosen to minimize frequency beat effects and right ventricular loading and to maximize left ventricular unloading. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  2. Risk Factors for Delayed Extubation after Ventricular Septal Defect Closure: a Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Divyakant Parmar

    Full Text Available Objective: The objective of our study was to determine the feasibility of early extubation and to identify the risk factors for delayed extubation in pediatric patients operated for ventricular septal defect closure. Methods: A prospective, observational study was carried out at our Institute. This study involved consecutive 135 patients undergoing ventricular septal defect closure. Patients were extubated if feasible within six hours after surgery. Based on duration of extubation, patients were divided two groups: Group 1= extubation time ≤ 6 hours, Group 2= extubation time >6 hours. Results: A total of 99 patients were in Group 1 and 36 patients in Group 2. Duration of ventilation was 4.4±0.9 hours in Group 1 and 25.9±24.9 hours in Group 2 (P<0.001. Univariate analysis showed that young age, low weight, low partial pressure of oxygen, trisomy 21, multiple ventricular septal defect, high vasoactive inotropic score, transient heart block and low cardiac output syndrome were associated with delayed extubation. However, regression analysis revealed that only trisomy 21 (OR: 0.248; 95%CI: 0.176-0.701; P=0.001, low cardiac output syndrome (OR: 0.291; 95%CI: 0.267-0.979; P=0.001, multiple ventricular septal defect (OR: 0.243; 95%CI: 0.147-0.606; P=0.002 and vasoactive inotropic score (OR: 0.174 95%CI: 0.002-0.062; P=0.039 are strongest predictors for delayed extubation. Conclusion: Trisomy 21, low cardiac output syndrome, multiple ventricular septal defect and high vasoactive inotropic score are significant risk factors for delay in extubation. Age, weight, pulmonary artery hypertension, size of ventricular septal defect, aortic cross-clamp and cardiopulmonary bypass time did not affect early extubation.

  3. [Dynamic changes of IL-1β in rat myocardium during hypoxia/ reoxygenation transition].

    Science.gov (United States)

    He, Jin-bo; Bao, Cai-ying; Ye, Yu-zhu; Luo, Zi-yin; Ying, Lei; Wang, Wan-tie

    2015-01-01

    To investigate the expression profile of interleuki-1β (IL-1β) in rat myocardium at different time points during hypoxia/reoxygenation(H/R)transition. The isolated Langendorff perfused rat heart model was established.Forty SD rats were randomly divided into sham group (A group) and hypoxia/reoxygenation group (H/R group). The H/R group rats were subdivided into H/R 0.5 h group(B group), H/R 1 h group(C group), H/R 2 h group(D group)according to reoxygenation time. The left ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax) were continuously recorded. The concentration of interleukin-1β(IL-lβ) and creatine kinase-MB (CK-MB) in myocardium was measured by ELISA. The mRNA expression of IL-lβ in myocardium was determined by RT-PCR. Microstructure of myocardium was observed under light microscopy. The value of LVDP and ±dp/dtmax in hypoxia/reoxygenation group rat were significantly lower than that in sham group(P myocardium after myocardial hypoxia /reoxygenation in rats might lead to. ischemia/reperfusion injury.

  4. Diastolic Left Ventricular Dysfunction : A Clinical Appraisal

    NARCIS (Netherlands)

    Bronzwaer, J.G.F.

    2003-01-01

    Diastolic left ventricular (LV) distensibility is determined by the material properties of the LV wall and by LV geometry (i.e., LV shape, LV volume and LV wall thickness). These material properties are influenced both by the physical structure of the LV myocardium and by the dynamic process of

  5. Effects of Triple Cryoenergy Application on Lesion Formation and Coronary Arteries in the Developing Myocardium.

    Science.gov (United States)

    Krause, Ulrich; Abreu da Cunha, Filipe D; Backhoff, David; Jacobshagen, Claudius; Klehs, Sophia; Schneider, Heike E; Paul, Thomas

    2017-04-01

    To improve long-term outcome after cryoablation of substrates of supraventricular tachycardia, application of two and three consecutive freeze-thaw cycles has been performed. The effect of triple freeze-thaw cycles on lesion formation within developing myocardium and coronary arteries, however, has not been studied yet. In eight piglets (mean age 15 weeks, weight 15-20 kg), 30 cryolesions (three consecutive freeze-thaw cycles) were applied to the atrial aspect of both AV valve annuli (n = 18) as well as to ventricular myocardium below the valves (n = 12). Coronary angiography was performed before and after cryoenergy application. The animals were reevaluated by coronary angiography and intracoronary ultrasound (ICUS) after 48 h. All hearts were removed for histological examination of the lesions subsequently. After staining (hematoxylin-eosin, desmin immunohistochemistry), lesions was measured by planimetry with a digital virtual miscroscope analysis system and volumes of the cryolesions were calculated. Mean atrial lesion volume was 190.68 ± 167.53 mm(3) (n = 18), and mean ventricular lesion volume was 184.34 ± 107.42 mm(3) (n = 12). Compared with previously reported data on lesion volumes after single and double freeze-thaw cycles, lesions were significantly larger. Coronary arteries were unaffected on coronary angiography as well as on ICUS. No affection of coronary arteries was found on histological examination. Application of three consecutive freeze-thaw cycles resulted in increased lesion volume compared with single and double freeze-thaw cycles. No affection of the coronary arteries was evident. To evaluate the clinical benefit and safety of triple cryoenergy application for catheter ablation, prospective randomized trials are required.

  6. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

    Directory of Open Access Journals (Sweden)

    Elena Qirjazi

    Full Text Available The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia.We conducted a population-based retrospective cohort study of older adults (mean age 76 years from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701 or escitalopram (n = 38 436, compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620. After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days.Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29, and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18. Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68, but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18.Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

  7. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

    Science.gov (United States)

    Qirjazi, Elena; McArthur, Eric; Nash, Danielle M; Dixon, Stephanie N; Weir, Matthew A; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J; Oliver, Matthew J; Wald, Ron; Garg, Amit X

    2016-01-01

    The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

  8. The amount of viable and dyssynchronous myocardium is associated with response to cardiac resynchronization therapy: initial clinical results using multiparametric ECG-gated [18F]FDG PET.

    Science.gov (United States)

    Lehner, Sebastian; Uebleis, Christopher; Schüßler, Franziska; Haug, Alexander; Kääb, Stefan; Bartenstein, Peter; Van Kriekinge, Serge D; Germano, Guido; Estner, Heidi; Hacker, Marcus

    2013-12-01

    There is still a significant amount of patients who do not sufficiently respond to cardiac resynchronization therapy (CRT). Previous studies demonstrated that the amount of dyssynchronous myocardium was predictive of response to CRT. Otherwise, non-response is frequently associated with high amounts of scar tissue. The combination of these parameters might yield a more accurate prediction of response. We hypothesized that the probability of a CRT response increases with the presence of high amounts of "viable and dyssynchronous" myocardium. A total of 19 patients (17 male, 61 ± 10 years) underwent ECG-gated [(18)F]fluorodeoxyglucose (FDG) myocardial positron emission tomography (PET) before CRT device implantation and were followed for 6 months. Response to CRT was defined as clinical improvement of at least one New York Heart Association (NYHA) class in combination with left ventricular (LV) ejection fraction (EF) improvement of >5%. Twelve responders (71%) and seven non-responders (29%) were identified. For each patient bullseye maps of FDG uptake and phase analysis were calculated (QPS/QGS 2012, Cedars-Sinai, Los Angeles, CA, USA) and fused. Amounts of myocardium representing "viable and synchronous", "scar and synchronous", viable and dyssynchronous or "scar and dyssynchronous" myocardium were quantified by planimetric measurements of the fused bullseye maps. Responders by definition showed significant decrease in NYHA class and significant increase of LVEF. Furthermore, a significantly higher amount of viable and dyssynchronous myocardium was found as compared to non-responders (21 ± 13% vs 6 ± 5%; p < 0.05). Combined assessment of myocardial viability and LV dyssynchrony is feasible using multiparametric [(18)F]FDG PET and could improve conventional response prediction criteria for CRT.

  9. A new cryoenergy for ventricular tachycardia ablation: a proof-of-concept study.

    Science.gov (United States)

    Berte, Benjamin; Sacher, Frédéric; Wielandts, Jean-Yves; Mahida, Saagar; Pillois, Xavier; Weerasooriya, Rukshen; Bernus, Olivier; Jaïs, Pierre

    2017-08-01

    Lack of transmural lesion formation during radiofrequency (RF) ablation for ventricular tachycardia (VT) is an important determinant of arrhythmia recurrence. The aim of this proof-of-concept study was to evaluate safety and efficacy of a new and more powerful cryoablation system for ventricular ablation. Five healthy female sheep (59 ± 6 kg) underwent a surgical sternotomy for epicardial and endocardial access [endocardial access via right atrial appendage and left ventricular (LV) apex]. A cryoablation system with liquid nitrogen (IceCure) was used to create 3 min freezes at the right ventricle (RV). Left ventricular cryoablation was performed with either a 6 min or 2 × 4 min freezes. To assess safety, ablation was also performed on the mid left anterior descending artery and the proximal coronary sinus. A total of 45 lesions were created (RV epicardial, n = 12; LV epicardial, n = 18; RV endocardial, n = 7; LV endocardial, n = 8; LAD, n = 4; and CS, n = 4). The mean lesion volume was 5055 ± 92 mm3 (length: 32 ± 4.6 mm, width: 16.0 ± 6.4 mm, and depth: 11.2 ± 4.4 mm). Lesions were transmural in 28/45 (62%) and >10 mm in depth in 35/45 (78%). Of the endocardial lesions, 12/15 were transmural (80%). There was no benefit of the bonus freeze in LV lesions (6 vs. 2 × 4 min: 6790 ± 44 vs. 5595 ± 63 mm3; P = 0.44). All ablated vascular structures appeared macroscopically normal without acute stenosis. One animal died due to incessant Ventricular fibrillation (VF). Our results indicate that a more powerful cryoablation system is able to create large, transmural ventricular lesions from both the endocardium and the epicardium. The technology may hold potential for both surgical and catheter-based VT ablation in humans.

  10. An Inverse Finite Element Method for Determining the Tissue Compressibility of Human Left Ventricular Wall during the Cardiac Cycle

    Science.gov (United States)

    Hassaballah, Abdallah I.; Hassan, Mohsen A.; Mardi, Azizi N.; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium’s tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle. PMID:24367544

  11. [Viable myocardium detecting by CARTO voltage mapping in swine model of acute myocardial infarction].

    Science.gov (United States)

    Lin, Tao; Ma, Yi-Tong; Yang, Yi-Ning; Mu, Hu-Yati; He, Peng-Yi; Yang, Yu-Chun; Chou, Ping; Liu, Fen; Zhang, Yan-Yi

    2010-08-01

    To evaluate the accuracy and practicability of detecting viable myocardium by CARTO voltage mapping in swine model of acute myocardial infarction (MI). MI was induced in 13 anesthetized swines via occluding the distal of left anterior descending coronary arteries by angioplasty balloon for 60-90 minutes. The viable myocardium detection by CARTO voltage mapping was made after reconstruction of the left ventricle using CARTO and the results were compared with TTC staining. The standard of CARTO voltage to detect viable myocardium was 0.5 - 1.5 mV while viable myocardium showed pink color by TTC staining. Eleven out of 13 swines survived the operation and 2 swines died of ventricular fibrillation at 45 and 65 minutes post ischemia. Left ventricle was divided into 16 segments and 176 segments from 11 swines were analyzed. Viable myocardium detected by CARTO voltage mapping was identical as identified by TTC staining (Kappa = 0.816, P < 0.001). Taken the TTC result as standard, the sensitivity, specificity and accuracy rate of CARTO voltage mapping are 71.8%, 96.5% and 90.9% respectively. CARTO voltage mapping could be used as a reliable tool to detect viable myocardium in this model.

  12. Left ventricular function during transluminal angioplasty: a haemodynamic and angiographic study

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); W. Wijns (William); M.J.B.M. van den Brand (Marcel); S. Mey (Simon); J.C.H. Schuurbiers (Johan); P.G. Hugenholtz (Paul); R.W. Brower (Ronald); C.J. Slager (Cornelis)

    1984-01-01

    textabstractThe response of left ventricular function, was studied in a series of patients undergoing percutaneous transluminal coronary angioplasty (PTCA). From 4 to 6 balloon inflations procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD),

  13. Evaluation of adenosine preconditioning with {sup 99m}Tc-His{sub 10}-annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Ye Fei [Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Fang Wei [Cardiovascular Institute and Fuwai Hospital, No. 167 Bei-Li-Shi-Lu, Beijing 100037 (China); Wang Feng, E-mail: fengwang1972cn@gmail.co [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Hua Zichun [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Wang Zizheng [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Yang Xiang [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2011-05-15

    Purpose: The goal of this study was to evaluate the feasibility of {sup 99m}Tc-His{sub 10}-annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods: {sup 99m}Tc-His{sub 10}-annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of {sup 99m}Tc-His{sub 10}-annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20-30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model (n=14). Adenosine was infused intravenously in six pigs before coronary occlusion. {sup 99m}Tc-His{sub 10}-annexin V (n=12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with {sup 99m}Tc-MIBI was also performed 1 day after His{sub 10}-annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results: {sup 99m}Tc-His{sub 10}-annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of {sup 99m}Tc-His{sub 10}-annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His{sub 10}-annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of {sup 99m}Tc-His{sub 10}-annexin was found in the risk area which showed no defects in the {sup 99m}Tc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly

  14. Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis.

    Science.gov (United States)

    Ajijola, Olujimi A; Lux, Robert L; Khahera, Anadjeet; Kwon, OhJin; Aliotta, Eric; Ennis, Daniel B; Fishbein, Michael C; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2017-03-01

    The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation

  15. Arrhythmogenic right ventricular dysplasia: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Wall, E.E. van der; Bootsma, M.M.; Schalij, M.J. [Dept. of Cardiology, Leiden Univ. Medical Center, Leiden (Netherlands); Kayser, H.W.M.; Roos, A. de [Dept. of Radiology, Leiden Univ. Medical Center, Leiden (Netherlands)

    2000-06-01

    Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown cause that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. Clinical manifestations include structural and functional malformations of the right ventricle, electrocardiographic abnormalities, and presentation with ventricular tachycardias with left bundle branch pattern or sudden death. The disease is often familial with an autosomal inheritance. In addition to right ventricular dilatation, right ventricular aneurysms are typical deformities of ARVD and they are distributed in the so-called ''triangle of dysplasia'', i. e., right ventricular outflow tract, apex, and infundibulum. Ventricular aneurysms at these sites can be considered pathognomonic of ARVD. Another typical hallmark of ARVD is fibrofatty infiltration of the right ventricular free wall. These functional and morphologic characteristics are relevant to clinical imaging investigations such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and magnetic resonance imaging (MRI). Among these techniques, MRI allows the clearest visualization of the heart, in particular because the right ventricle is involved, which is usually more difficult to explore with the other imaging modalities. Furthermore, MRI offers the specific advantage of visualizing adipose infiltration as a bright signal of the right ventricular myocardium. MRI provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD within one single study. As a result, MRI appears to be the optimal imaging technique for detecting and following patients with clinical suspicion of ARVD. (orig.) [German] Die arrhythmogene rechtsventrikulaere Dysplasie (ARVD), eine Herzmuskelerkrankung unklarer Aetiologie, ist pathologisch durch fettige Degeneration des rechtsventrikulaeren Myokards gekennzeichnet. Die klinischen Symptome

  16. [Left ventricular functions in patients with cardiac syndrome X: a tissue Doppler study].

    Science.gov (United States)

    Yazici, Hüseyin Uğur; Sen, Nihat; Tavil, Yusuf; Hizal, Fatma; Turfan, Murat; Poyraz, Fatih; Boyaci, Bülent; Cengel, Atiye

    2009-12-01

    The aim of the study was to compare diagnostic accuracy of tissue Doppler imaging (TDI) and conventional Doppler echocardiography in diagnosis of left ventricular diastolic dysfunction in patients with cardiac syndrome X. Our study was designed as cross-sectional study. In our study, we compared 35 patients with cardiac syndrome X (19 female, mean age 47.2+/- 7.3 years) with 33 healthy persons as control group (18 female, mean age 49.5+/- 7.1 years) with no coronary artery disease and having no ischemic complaints or findings at exercise test. Left ventricular systolic function was found by considering mean values of modified Simpson method for left ventricular ejection fraction and TDI assessment of systolic wave peak velocity. The diastolic function of left ventricle was assessed with conventional echocardiography and TDI. Unpaired t test for independent samples or Mann-Whitney U test were used for comparison of continuous variables, Chi square test - for comparison of categorical variables. To define the capability of predicting diastolic dysfunction for conventional Doppler echocardiography and tissue Doppler imaging ROC curve analysis was applied. Left ventricular ejection fraction and systolic wave peak velocity were similar for both groups. Conventional Doppler echocardiographic measurements for left ventricular diastolic functions delineated the more frequent presence of diastolic dysfunction in cardiac syndrome X group As compared with controls (48% vs 18%; p<0.01). When both methods used for assessing diastolic dysfunction, it was found more apparent (66% vs 24%; p<0.01). When ROC curve was drawn for conventional Doppler echocardiography the AUC was 0.623, the sensitivity and the specificity were 49% and 76%, respectively. When the same was done for TDI the values were AUC=0.669, the sensitivity - 66% and the specificity - 68%. Our study revealed the deterioration of left ventricular diastolic function in patients with cardiac syndrome X. We found TDI

  17. Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

    Science.gov (United States)

    Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

    2017-06-06

    We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Gender differences in left ventricular structure and function during antihypertensive treatment: the Losartan Intervention for Endpoint Reduction in Hypertension Study

    DEFF Research Database (Denmark)

    Gerdts, E.; Okin, P.M.; Simone, G. de

    2008-01-01

    In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point...... hypertrophy regression during long-term antihypertensive treatment Udgivelsesdato: 2008/4...

  19. Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of randomized comparative studies.

    Science.gov (United States)

    Fagard, Robert H; Celis, Hilde; Thijs, Lutgarde; Wouters, Stijn

    2009-11-01

    Blood pressure-lowering therapy reduces left ventricular mass, but the question of whether differences exist among drug classes has not been fully resolved. Our aim was to compare the effects of diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers on left ventricular mass regression in patients with hypertension on the basis of prospective, randomized comparative studies. We performed meta-analyses, involving pooled pairwise comparisons of the drug classes and of each class versus other classes statistically combined, and meta-regression analyses to identify the determinants of the regression. The 75 relevant publications involved 84 pairwise comparisons and 6001 patients. Regression of left ventricular mass was significantly less (P=0.01) with beta-blockers (9.8%) than with angiotensin receptor blockers (12.5%), but none of the other analyzable pairwise comparisons between drug classes revealed significant differences (P>0.10). In addition, beta-blockers showed less regression than the other 4 classes statistically combined (Pmeta-regression analysis on all of the treatment arms, beta-blocker treatment was a significant and negative predictor of the regression (-3.6%; Pclasses, including angiotensin receptor blockers. In conclusion, beta-blockers show less regression of left ventricular mass, whereas angiotensin receptor blockers may induce larger regression. The inferiority of beta-blockers appears to be more convincing than the superiority of angiotensin receptor blockers.

  20. Right ventricular dysfunction in patients with Brugada-like electrocardiography: a two dimensional strain imaging study

    Directory of Open Access Journals (Sweden)

    Murata Kazuya

    2011-11-01

    Full Text Available Abstract Background Sodium channel blockers augment ST-segment elevation in the right precordial leads in patients undergoing Brugada-type electrocardiography (ECG. However, their effect on echocardiographic features is not known. We address this by assessing global and regional ventricular function using conventional Doppler and two- dimensional (2D speckle tracking techniques. Methods Thirty-one patients with Brugada-type ECG were studied. A pure sodium channel blocker, pilsicainide, was used to provoke an ECG response. The percentage longitudinal systolic myocardial strain at the base of both the right ventricular (RV free wall and the interventricular septum wall was measured using 2D speckle tracking. Left ventricular (LV and RV myocardial performance (TEI indices were also measured. Results The pilsicainide challenge provoked a positive ECG response in 13 patients (inducible group. In the inducible group, longitudinal strain was significantly reduced only at the RV (-27.3 ± 5.4% vs -22.1 ± 3.6%, P P P Conclusions Temporal and spatial analysis using the TEI index and 2D strain imaging revealed the deterioration of global ventricular function associated with conduction disturbance and RV regional function in patients with Brugada-type ECG and coved type ST elevation due to administration of a sodium channel blocker.

  1. Experimental Study on the Mechanism o£ Cardiac Failure in the Diffuse Anoxia and Acute Local Ischemia of Myocardium in Dogs

    Directory of Open Access Journals (Sweden)

    Nasser Guiti

    1971-07-01

    Full Text Available The acute diffuse hypoxia in dogs by general hypoxia, ligation of the coronary arteries and perfusion of the coronaries in the diffuse hypoxic hear ts. T he results of our experiments suggest that the quantitative diminu tion of oxygen and bloo d supply to the myocardium is, rather than oxygen differential , a determining fa ctor for development of ventr icular fi brillat ion or cardiac arrest.

  2. Cardiac "fitness" training: an experimental comparative study of three methods of pulmonary artery banding for ventricular training.

    Science.gov (United States)

    Le Bret, Emmanuel; Lupoglazoff, Jean Marc; Borenstein, Nicolas; Fromont, Gaelle; Laborde, François; Bachet, Jean; Vouhé, Pascal

    2005-01-01

    When the left ventricle is unable to sustain a systemic pressure in transposition of the great arteries (TGA), left ventricular retraining is mandatory before the morphologic left ventricle under the aorta is switched. This is currently achieved by creating a ventricular overload through pulmonary artery banding, usually associated with an aortopulmonary shunt in case of a TGA with an intact ventricular septum. Our experimental study compared three different modes of increased ventricular afterload to obtain ventricular hypertrophy. Fifteen lambs (mean weight 48 kg) underwent pulmonary artery banding. Five animals (group I) received a classic band; 5 (group II) received a classic band which was adjusted at week 1 and 3; and 4 (group III) received a band which was tightened for 1 hour, twice a day (early morning and late afternoon). After 5 weeks, the lambs were evaluated hemodynamically before they were sacrificed and their hearts harvested for histologic examination. No difference was noted in the hemodynamic data between groups 1 and II. Group III showed a greater ability to increase ventricular pressure in this model. No significant difference was noted between the three groups in terms of macroscopic alterations, but all animals demonstrated an increase in right ventricular wall thickness compared with control animals. Several fibrosis areas were evident in group I and II but none in group III. Intermittent pulmonary artery banding is able to induce hemodynamically sufficient ventricular hypertrophy without fibrosis.

  3. Arrhythmogenic right ventricular cardiomyopathy in a dog : case report

    Directory of Open Access Journals (Sweden)

    A.J. Möhr

    2000-07-01

    Full Text Available An 8-month-old Labrador retriever bitch was evaluated for sudden-onset, progressive abdominal distension. Physical examination revealed an exaggerated inspiratory effort, severe ascites, bilateral jugular vein distension, and hypokinetic femoral arterial pulses. Thoracic auscultation detected tachycardia with muffled heart sounds, without audible cardiac murmurs. Thoracic radiographs identified severe right ventricular enlargement and pleural effusion. The electrocardiogram was consistent with incomplete right bundle branch block or right ventricular enlargement. Echocardiography demonstrated severe right ventricular and atrial dilation, secondary tricuspid regurgitation, and thinning and hypocontractility of the right ventricular myocardium. Left heart chamber sizes were slightly decreased, with normal left ventricular contractility. Adiagnosis of arrhythmogenic right ventricular cardiomyopathy was reached, based on the characteristic clinical, electrocardiographic, radiographic and echocardiographic findings, and the exclusion of other causes of isolated right ventricular failure. Treatment effected good control of clinical signs, until acutely decompensated congestive right heart failure led to euthanasia after 4 months. Arrhythmogenic right ventricular cardiomyopathy is a well-described clinical entity in humans, and has previously been documented in 3 male dogs. The condition is characterised by progressive fibro-adipose replacement of right ventricular myocardium, while the left ventricle usually remains unaffected. It should be considered a differential diagnosis in any young dog presented with isolated right heart failure, syncope, or unexplained ventricular tachyarrhythmias. This article reports the 1st case of arrhythmogenic right ventricular cardiomyopathy in a female dog, and highlights its echocardiographic features.

  4. [Effect of spironolactone in patients with heart failure and preserved left ventricular function - TOPCAT study].

    Science.gov (United States)

    Widimský, Jiří

    2015-05-01

    The TOPCAT study followed the effect of spironolactone on a chronic heart failure with a preserved left ventricular ejection fraction. The study did not find any impact on the primary goal of the study, i.e. a combination of cardiovascular mortality, managed cardiac arrest or hospitalization rate for heart failure treatment. The only finding of the study was the decrease in hospitalization rates for a heart failure. A post hoc analysis, however, identified a significant difference between patients from the Americas (USA, Canada, Argentina, Brazil) on the one hand and those from Russia/Georgia on the other. The differences were rather striking. Whereas the former manifested a significant reduction in the incidence of the primary goal, i.e. cardiovascular mortality and hospitalization with heart failure through treatment with spironolactone, the incidence of all clinical events was considerably lower in Russia/Georgia and no impact of spironolactone at all on any of the goals was identified regarding the patients from Russia/Georgia. This post hoc analysis therefore suggested a possible therapeutic effect of spironolactone in the Americas, as well as in the populations of similar characteristics. Most studies accept a definition only based on the heart failure with a preserved left ventricular ejection fraction. The study points to the need to further elaborate this definition which also has to consider changes of the left ventricular diastolic function when defining a diastolic heart failure.

  5. Mature fat cells in the myocardium of patients with tuberous sclerosis complex

    NARCIS (Netherlands)

    Adriaensen, M.E.; Oosterhout, M.F. van; Feringa, H.H.; Schaefer-Prokop, C.M.; Zonnenberg, B.A.; Prokop, M.

    2011-01-01

    AIM: Routine abdominal CT scans in patients with tuberous sclerosis complex (TSC) showed characteristic fatty foci in the depicted caudal portions of the myocardium. The purpose of this study was to investigate if areas of abnormal myocardium in patients with TSC could also be found in post-mortem

  6. Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency

    NARCIS (Netherlands)

    D. Fan (Dongsheng); L.K. Soei (Lou Kie); L.M. Sassen; R. Krams (Rob); P.D. Verdouw (Pieter)

    1994-01-01

    textabstractOxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium,

  7. Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium

    Science.gov (United States)

    Razumova, Maria V.; Stelzer, Julian E.; Norman, Holly S.; Moss, Richard L.

    2011-01-01

    Myosin heavy chain (MHC) isoforms are principal determinants of work capacity in mammalian ventricular myocardium. The ventricles of large mammals including humans normally express ∼10% α-MHC on a predominantly β-MHC background, while in failing human ventricles α-MHC is virtually eliminated, suggesting that low-level α-MHC expression in normal myocardium can accelerate the kinetics of contraction and augment systolic function. To test this hypothesis in a model similar to human myocardium we determined composite rate constants of cross-bridge attachment (fapp) and detachment (gapp) in porcine myocardium expressing either 100% α-MHC or 100% β-MHC in order to predict the MHC isoform-specific effect on twitch kinetics. Right atrial (∼100% α-MHC) and left ventricular (∼100% β-MHC) tissue was used to measure myosin ATPase activity, isometric force, and the rate constant of force redevelopment (ktr) in solutions of varying Ca2+ concentration. The rate of ATP utilization and ktr were approximately ninefold higher in atrial compared with ventricular myocardium, while tension cost was approximately eightfold greater in atrial myocardium. From these values, we calculated fapp to be ∼10-fold higher in α- compared with β-MHC, while gapp was 8-fold higher in α-MHC. Mathematical modeling of an isometric twitch using these rate constants predicts that the expression of 10% α-MHC increases the maximal rate of rise of force (dF/dtmax) by 92% compared with 0% α-MHC. These results suggest that low-level expression of α-MHC significantly accelerates myocardial twitch kinetics, thereby enhancing systolic function in large mammalian myocardium. PMID:21217059

  8. Alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion.

    Science.gov (United States)

    Rodriguez, Filiberto; Langer, Frank; Harrington, Katherine B; Cheng, Allen; Daughters, George T; Criscione, John C; Ingels, Neil B; Miller, D Craig

    2005-04-01

    Helically oriented left ventricular fibers assemble into transmural sheets, which are important for wall-thickening mechanics: 15% fiber shortening results in 40% cross-fiber left ventricular wall thickening and a 60% ejection fraction through sheet extension, thickening, and shear. Normal cardiac microstructure and strains are optimized; deviations could result in apoptosis and deleterious matrix remodeling, which degenerates into global cardiomyopathy. We studied alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion. Nine sheep had radiopaque markers implanted to measure left ventricular systolic fractional area shortening; 3 transmural bead columns were inserted into the midlateral wall for strain analysis. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during 70 seconds of ischemia. Systolic strains were quantified along circumferential, longitudinal, and radial axes (n = 9) and were transformed into fiber-sheet coordinates by using quantitative microstructural measurements (n = 5). A functional border was defined in the midlateral left ventricle; ischemia decreased posterolateral fractional area shortening, and anterolateral fractional area shortening increased. In this demarcation junction, subepicardial end-systolic radial wall thickening decreased (0.16 +/- 0.08 vs 0.11 +/- 0.06) and sheet-normal shear was abolished (0.08 +/- 0.04 vs -0.01 +/- 0.03). Longitudinal shortening decreased in the subepicardium and midwall (-0.05 +/- 0.04 vs +/- -0.01 +/- 0.06), but circumferential-radial shear increased at these depths (0.04 +/- 0.04 vs 0.11 +/- 0.05). Subendocardial fiber stretch occurred during early systole (-0.01 +/- 0.03 vs 0.02 +/- 0.03), and end-systolic fiber-sheet shear increased (0.07 +/- 0.01 vs 0.11 +/- 0.04, all P < .05). Increased circumferential-radial shear and altered fiber-sheet strains reflect mechanical interactions between ischemic and nonischemic

  9. Comparative studies on right ventricular pressure and volume overloading by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Owada, K.; Tsukahara, Y.; Kijima, M.; Miyazaki, Y.; Ono, K. (Fukushima Medical Coll. (Japan))

    1982-03-01

    Thallium-201 myocardial scintigraphy was performed in 44 patients with various heart diseases including mitral stenosis, atrial septal defect, primary pulmonary hypertension, and left atrial myxoma. The morphological findings of right ventricular (RV) free wall on the scintigram and RV/IVS (interventricular septum) uptake ratio of the images obtained from the left anterior oblique projection were studied in the patients with RV pressure or volume overloading.

  10. Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: a post-hoc analysis of the Hokusai-VTE study

    NARCIS (Netherlands)

    Brekelmans, Marjolein P. A.; Ageno, Walter; Beenen, Ludo F.; Brenner, Benjamin; Buller, Harry R.; Chen, Cathy Z.; Cohen, Alexander T.; Grosso, Michael A.; Meyer, Guy; Raskob, Gary; Segers, Annelise; Vanassche, Thomas; Verhamme, Peter; Wells, Philip S.; Zhang, George; Weitz, Jeffrey I.

    2016-01-01

    Background In patients with pulmonary embolism, right ventricular dysfunction is associated with early mortality. The Hokusai-VTE study used N-terminal pro-brain natriuretic peptide (NT-proBNP) and right to left ventricular diameter ratio on CT as indicators of right ventricular dysfunction and

  11. Right ventricular dysfunction affects survival after surgical left ventricular restoration.

    Science.gov (United States)

    Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

    2017-04-01

    Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left

  12. Improved identification of viable myocardium using second harmonic imaging during dobutamine stress echocardiography

    OpenAIRE

    Sozzi, Fabiola; Poldermans, Don; Bax, Jeroen; Elhendy, Abdou; Vourvouri, Eleni; Valkema, Roelf; Sutter, J.; Schinkel, Arend; Borghetti, A; Roelandt, Jos

    2001-01-01

    OBJECTIVE—To determine whether, compared with fundamental imaging, second harmonic imaging can improve the accuracy of dobutamine stress echocardiography for identifying viable myocardium, using nuclear imaging as a reference.
PATIENTS—30 patients with chronic left ventricular dysfunction (mean (SD) age, 60 (8) years; 22 men).
METHODS—Dobutamine stress echocardiography was carried out in all patients using both fundamental and second harmonic imaging. All patients underwent dual isotope simul...

  13. Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study.

    Science.gov (United States)

    Kaye, Gerald C; Linker, Nicholas J; Marwick, Thomas H; Pollock, Lucy; Graham, Laura; Pouliot, Erika; Poloniecki, Jan; Gammage, Michael

    2015-04-07

    Chronic right ventricle (RV) apical (RVA) pacing is standard treatment for an atrioventricular (AV) block but may be deleterious to left ventricle (LV) systolic function. Previous clinical studies of non-apical pacing have produced conflicting results. The aim of this randomized, prospective, international, multicentre trial was to compare change in LV ejection fraction (LVEF) between right ventricular apical and high septal (RVHS) pacing over a 2-year study period. We randomized 240 patients (age 74 ± 11 years, 67% male) with a high-grade AV block requiring >90% ventricular pacing and preserved baseline LVEF >50%, to receive pacing at the RVA (n = 120) or RVHS (n = 120). At 2 years, LVEF decreased in both the RVA (57 ± 9 to 55 ± 9%, P = 0.047) and the RVHS groups (56 ± 10 to 54 ± 10%, P = 0.0003). However, there was no significant difference in intra-patient change in LVEF between confirmed RVA (n = 85) and RVHS (n = 83) lead position (P = 0.43). There were no significant differences in heart failure hospitalization, mortality, the burden of atrial fibrillation, or plasma brain natriutetic peptide levels between the two groups. A significantly greater time was required to place the lead in the RVHS position (70 ± 25 vs. 56 ± 24 min, P < 0.0001) with longer fluoroscopy times (11 ± 7 vs. 5 ± 4 min, P < 0.0001). In patients with a high-grade AV block and preserved LV function requiring a high percentage of ventricular pacing, RVHS pacing does not provide a protective effect on left ventricular function over RVA pacing in the first 2 years. ClinicalTrials.gov number NCT00461734. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  14. Probability mapping of scarred myocardium using texture and intensity features in CMR images.

    Science.gov (United States)

    Kotu, Lasya Priya; Engan, Kjersti; Skretting, Karl; Måløy, Frode; Orn, Stein; Woie, Leik; Eftestøl, Trygve

    2013-09-22

    The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium).

  15. Probability mapping of scarred myocardium using texture and intensity features in CMR images

    Science.gov (United States)

    2013-01-01

    Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

  16. The reliability of echocardiographic left ventricular wall motion index to identify high-risk patients for multicenter studies

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Gadsbøll, Niels; Quinones, Miguel A

    2006-01-01

    OBJECTIVE: To study whether the use of echocardiographic left ventricular (LV) wall motion index (WMI) is a dependable parameter for identifying patients with LV dysfunction to be enrolled in multicenter trials. METHODS: Videotaped echocardiographic examinations from 200 randomly selected patient...

  17. Ventricular dyssynchrony assessed by gated myocardial perfusion SPECT using a geometrical approach: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Veen, Berlinda J. van der; Younis, Imad Al [Leiden University Medical Centre, Department of Nuclear Medicine, Leiden (Netherlands); Ajmone-Marsan, Nina; Bax, Jeroen J. [Leiden University Medical Centre, Department of Cardiology, Leiden (Netherlands); Westenberg, Jos J.M.; Roos, Albert de [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Stokkel, Marcel P.M. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2012-03-15

    Left ventricular dyssynchrony may predict response to cardiac resynchronization therapy and may well predict adverse cardiac events. Recently, a geometrical approach for dyssynchrony analysis of myocardial perfusion scintigraphy (MPS) was introduced. In this study the feasibility of this geometrical method to detect dyssynchrony was assessed in a population with a normal MPS and in patients with documented ventricular dyssynchrony. For the normal population 80 patients (40 men and 40 women) with normal perfusion (summed stress score {<=}2 and summed rest score {<=}2) and function (left ventricular ejection fraction 55-80%) on MPS were selected; 24 heart failure patients with proven dyssynchrony on MRI were selected for comparison. All patients underwent a 2-day stress/rest MPS protocol. Perfusion, function and dyssynchrony parameters were obtained by the Corridor4DM software package (Version 6.1). For the normal population time to peak motion was 42.8 {+-} 5.1% RR cycle, SD of time to peak motion was 3.5 {+-} 1.4% RR cycle and bandwidth was 18.2 {+-} 6.0% RR cycle. No significant gender-related differences or differences between rest and post-stress acquisition were found for the dyssynchrony parameters. Discrepancies between the normal and abnormal populations were most profound for the mean wall motion (p value <0.001), SD of time to peak motion (p value <0.001) and bandwidth (p value <0.001). It is feasible to quantify ventricular dyssynchrony in MPS using the geometrical approach as implemented by Corridor4DM. (orig.)

  18. Comparison between right and left ventricular myocardia during the human fetal period. Stereological evaluation

    Directory of Open Access Journals (Sweden)

    Ricardo Xavier-Vidal

    1999-05-01

    Full Text Available PURPOSE: To develop a stereological comparison between right (RV and left ventricle (LV myocardium during the third human gestational trimester. METHODS: Five human fetal hearts of the third trimester provided representative samples of 5 RV myocardium and 4 LV myocardium. The material was fixed in 10% buffered formaldehyde, and processed through routine methods. Fifteen microscopic fields were randomly chosen and counted in each ventricular myocardium using an "M-42" test system. The following stereological parameters were assessed: Vv (%, Lv (µm², Sv (µm²/µm³, Vp (µm³, Nv (1/mm³ and total N. RESULTS: No significant difference between the stereological parameters of the myocardial structures assessed was evidenced, when comparing RV and LV. CONCLUSION: Right and left human ventricular myocardium are very similar during the fetal period at least in regard to their structural aspects.

  19. Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

    Science.gov (United States)

    Wenk, Jonathan F; Sun, Kay; Zhang, Zhihong; Soleimani, Mehrdad; Ge, Liang; Saloner, David; Wallace, Arthur W; Ratcliffe, Mark B; Guccione, Julius M

    2011-04-01

    Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure.

  20. Electrophysiologic study-guided amiodarone for sustained ventricular tachyarrhythmias associated with structural heart diseases.

    Science.gov (United States)

    Aiba, Takeshi; Yamagata, Kenichiro; Shimizu, Wataru; Taguchi, Atsushi; Satomi, Kazuhiro; Noda, Takashi; Okamura, Hideo; Suyama, Kazuhiro; Aihara, Naohiko; Kamakura, Shiro; Kurita, Takashi

    2008-01-01

    Although an electrophysiologic study (EPS) and Holter-monitoring are often helpful in evaluating the efficacy of antiarrhythmic drugs in patients with ventricular tachyarrhythmias (ventricular tachycardia/fibrillation (VT/VF)), the efficacy of EPS- or Holter-guided oral amiodarone therapy in Japanese patients is still unclear. EPS was performed 1 month after starting amiodarone, and Holter-monitoring was recorded before and 1 month after amiodarone in 188 patients with sustained VT/VF because of structural heart diseases. In spite of the judgment of EPS (n=89) or Holter (n=75), all patients continued amiodarone. Patients were followed up to 3 years and the primary endpoint was VT/VF recurrence and secondary endpoint was death by all cause. Kaplan-Meier estimated the risk of VT/VF recurrence was significantly smaller with EPS-guided amiodarone (pamiodarone. Multivariate Cox hazard analysis revealed that EPS-guided amiodarone was an independent factor suppressing the recurrence of VT/VF (pamiodarone was effective in patients with relatively well-preserved left ventricular ejection fraction (LVEF > or =0.30) but not in patients with lower LVEF (LVEF amiodarone was useful for preventing recurrence of VT/VF in patients with a relatively well-preserved LVEF, but not always beneficial in patients with a lower LVEF.

  1. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

    Science.gov (United States)

    Zhang, Xiaoli; Schindler, Thomas H.; Prior, John O.; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng

    2016-01-01

    Purpose The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Methods Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25±10 %) were studied with 13N-ammonia and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to 13N-ammonia activity ratios. Results Rest MBF was reduced in viable (0.42±0.18 ml/min per g) and nonviable regions (0.32±0.09 ml/min per g) relative to remote regions (0.68±0.23 ml/min per g, p0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39±0.56 vs 1.70±0.45, p>0.05) but were significantly lower in nonviable regions (1.23±0.43, pmyocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes. PMID:23287994

  2. Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

    Science.gov (United States)

    Li, Xiaorong; Zhang, Fengxiang; Song, Guixian; Gu, Weijuan; Chen, Minglong; Yang, Bing; Li, Dianfu; Wang, Daowu; Cao, Kejiang

    2013-01-01

    Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (pinfarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.

  3. Impact of left ventricular geometry on prognosis in hypertensive patients with left ventricular hypertrophy (the LIFE study)

    DEFF Research Database (Denmark)

    Gerdts, E.; Cramariuc, D.; Simone, G. de

    2008-01-01

    AIMS: Less is known about the relation between in-treatment left ventricular (LV) geometry and risk of cardiovascular events. We assessed LV geometric patterns on baseline and annual echocardiograms as time-varying predictors of the primary composite endpoint (cardiovascular death, stroke......, and myocardial infarction) in 937 hypertensive patients with LV hypertrophy during 4.8 years losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy. METHODS AND RESULTS: LV geometry was determined from LV mass/body surface area...... including LV geometric patterns as time-varying variables and adjusting for treatment, Framingham risk score, race, and time-varying systolic blood pressure, the patterns independently predicted higher risk of primary composite endpoints [HR 2.99 (1.16-7.71) for concentric remodelling, HR 1.79 (1...

  4. Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: intravital microscopic observation and (31)P-MR spectroscopic studies.

    Science.gov (United States)

    Homma, Satoshi; Kimura, Taizo; Sakai, Satoshi; Yanagi, Ken-ichi; Miyauchi, Yumi; Aonuma, Kazutaka; Miyauchi, Takashi

    2014-11-24

    Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We investigated the ameliorating effect of CGRP in myocardial ischemia induced by endothelin-1 (ET-1), with special emphasis on myocardial microvascular hemodynamics and levels of energy-related metabolites. The Langendorff preparations of rat isolated heart were perfused at a constant flow rate. Microvascular blood flow was also visualized in the anterior epicardium of the left ventricle by means of an intravital fluorescence microscope system. Energy-related metabolite contents in the myocardium were measured by means of (31)P-magnetic resonance spectroscopy ((31)P-MRS). Intracoronary bolus injections of CGRP caused dose-dependent decreases in coronary perfusion pressure (CPP) in the hearts exposed to ET-1 (30 pmol). The vasodilator potency of CGRP was about 10,000-fold greater than that of nitroglycerin and 1,000-fold greater than that of isobutylmethylxanthine. Vasodilation of the small-sized arterioles (10-40 μm in diameter) in response to CGRP (100 pmol) was confirmed by direct microscopic observation. After ET-1 (30 pmol) plus vehicle administration, high energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (pchanges in the myocardium (decrease in PCr) and macrohemodynamic alterations (increase in CPP, decrease in dP/dt etc.) induced by ET-1. We conclude that CGRP effectively confers hemodynamic and metabolic protections to isolated beating hearts against ET-1-induced myocardial ischemia. Copyright © 2014. Published by Elsevier Inc.

  5. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2017-06-09

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p Myocardial Damage in STEMI [LIPSIA-COND]; NCT02158468). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. A systematic review of left ventricular cardio-endoscopic surgery.

    Science.gov (United States)

    Soylu, Erdinc; Kidher, Emaddin; Ashrafian, Hutan; Stavridis, George; Harling, Leanne; Athanasiou, Thanos

    2017-05-25

    Better visualisation, accurate resection and avoidance of ventriculotomy associated with use of endoscopic devices during intracardiac surgery has led to increasing interest in their use. The possibility of combining a cardio-endoscopic technique with either minimally invasive or totally endoscopic cardiac surgery provides an incentive for its further development. Several devices have been used, however their uptake has been limited due to uncertainty around their impact on patient outcomes. A systematic review of the literature identified 34 studies, incorporating 54 subjects undergoing treatment of left ventricular tumours, thrombus or hypertrophic myocardium using a cardio-endoscopic technique. There were no mortalities (0%; 0/47). In 12 studies, the follow-up period was longer than 30 days. There were no post-operative complications apart from one case of atrial fibrillation (2.2%; 1/46). Complete resection of left ventricular lesion was achieved in all cases (100%; 50/50). These successful results demonstrate that the cardio-endoscopic technique is a useful adjunct in resection of left ventricular tumours, thrombus and hypertrophic myocardium. This approach facilitates accurate resection of pathological tissue from left ventricle whilst avoiding exposure related valvular damage and adverse effects associated with ventriculotomy. Future research should focus on designing adequately powered comparative randomised trials focusing on major cardiac and cerebrovascular morbidity outcomes in both the short and long-term. In this way, we may have a more comprehensive picture of both the safety and efficacy of this technique and determine whether such devices could be safely adopted for routine use in minimal access or robotic intra-cardiac surgery.

  7. Non-gated computed tomography of left ventricular hypertrophy. Comparison with vectorcardiogram

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Junta (Jikei Univ., Tokyo (Japan). School of Medicine)

    1983-08-01

    Non-ECG gated computed tomography (CT) of the heart was carried out in 19 cases with cardiovascular diseases; 4 with mitral stenosis, 3 with aortic valve disease, 2 with combined valve disease, 8 with hypertrophic cardiomyopathy and one myocardial infarction and one aortic aneurysm. All cardiac diseases were studied by echocardiography and 13 of them further investigated by intracadiac catheterization. The interventricular septum and the apical and posterolateral wall of the left ventricle were segmentally evaluated as to relative wall thickness of myocardium on CT. The wall thickness was directly measured on left ventricular cine angiograms in 13 cases. O-G vector calculated by CT was compatible with the palne of vectorcardiography in evaluating left ventricular hypertorphy. Conclusion were as follows: 1) The degree and site of myocardial hypertrophy were detected by CT with satisfaction. 2) The area of ventricular myocardium increased in aortic valve disease and hypertrophic cardiomyopathy. 3) The direction and magnitude of O-G vector calculated by CT were well correlated to the half area of QRS loop in horizontal plane of vectorcardiography.

  8. Pitx2c Is Reactivated in the Failing Myocardium and Stimulates Myf5 Expression in Cultured Cardiomyocytes

    Science.gov (United States)

    Torrado, Mario; Franco, Diego; Hernández-Torres, Francisco; Crespo-Leiro, María G.; Iglesias-Gil, Carmen; Castro-Beiras, Alfonso; Mikhailov, Alexander T.

    2014-01-01

    Background Pitx2 (paired-like homeodomain 2 transcription factor) is crucial for heart development, but its role in heart failure (HF) remains uncertain. The present study lays the groundwork implicating Pitx2 signalling in different modalities of HF. Methodology/Principal Findings A variety of molecular, cell-based, biochemical, and immunochemical assays were used to evaluate: (1) Pitx2c expression in the porcine model of diastolic HF (DHF) and in patients with systolic HF (SHF) due to dilated and ischemic cardiomyopathy, and (2) molecular consequences of Pitx2c expression manipulation in cardiomyocytes in vitro. In pigs, the expression of Pitx2c, physiologically downregulated in the postnatal heart, is significantly re-activated in left ventricular (LV) failing myocardium which, in turn, is associated with increased expression of a restrictive set of Pitx2 target genes. Among these, Myf5 was identified as the top upregulated gene. In vitro, forced expression of Pitx2c in cardiomyocytes, but not in skeletal myoblasts, activates Myf5 in dose-dependent manner. In addition, we demonstrate that the level of Pitx2c is upregulated in the LV-myocardium of SHF patients. Conclusions/Significance The results provide previously unrecognized evidence that Pitx2c is similarly reactivated in postnatal/adult heart at distinct HF phenotypes and suggest that Pitx2c is involved, directly or indirectly, in the regulation of Myf5 expression in cardiomyocytes. PMID:24595098

  9. Pitx2c is reactivated in the failing myocardium and stimulates myf5 expression in cultured cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Mario Torrado

    Full Text Available BACKGROUND: Pitx2 (paired-like homeodomain 2 transcription factor is crucial for heart development, but its role in heart failure (HF remains uncertain. The present study lays the groundwork implicating Pitx2 signalling in different modalities of HF. METHODOLOGY/PRINCIPAL FINDINGS: A variety of molecular, cell-based, biochemical, and immunochemical assays were used to evaluate: (1 Pitx2c expression in the porcine model of diastolic HF (DHF and in patients with systolic HF (SHF due to dilated and ischemic cardiomyopathy, and (2 molecular consequences of Pitx2c expression manipulation in cardiomyocytes in vitro. In pigs, the expression of Pitx2c, physiologically downregulated in the postnatal heart, is significantly re-activated in left ventricular (LV failing myocardium which, in turn, is associated with increased expression of a restrictive set of Pitx2 target genes. Among these, Myf5 was identified as the top upregulated gene. In vitro, forced expression of Pitx2c in cardiomyocytes, but not in skeletal myoblasts, activates Myf5 in dose-dependent manner. In addition, we demonstrate that the level of Pitx2c is upregulated in the LV-myocardium of SHF patients. CONCLUSIONS/SIGNIFICANCE: The results provide previously unrecognized evidence that Pitx2c is similarly reactivated in postnatal/adult heart at distinct HF phenotypes and suggest that Pitx2c is involved, directly or indirectly, in the regulation of Myf5 expression in cardiomyocytes.

  10. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function

    Science.gov (United States)

    Saxena, Amit; Dobaczewski, Marcin; Rai, Vikrant; Haque, Zaffar; Chen, Wei; Li, Na

    2014-01-01

    Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3EGFP reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24–72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of α-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling. PMID:25128167

  11. A Kinase-Independent Function of c-Src Mediates p130Cas Phosphorylation at the Serine-639 Site in Pressure Overloaded Myocardium.

    Science.gov (United States)

    Palanisamy, Arun P; Suryakumar, Geetha; Panneerselvam, Kavin; Willey, Christopher D; Kuppuswamy, Dhandapani

    2015-12-01

    Early work in pressure overloaded (PO) myocardium shows that integrins mediate focal adhesion complex formation by recruiting the adaptor protein p130Cas (Cas) and nonreceptor tyrosine kinase c-Src. To explore c-Src role in Cas-associated changes during PO, we used a feline right ventricular in vivo PO model and a three-dimensional (3D) collagen-embedded adult cardiomyocyte in vitro model that utilizes a Gly-Arg-Gly-Asp-Ser (RGD) peptide for integrin stimulation. Cas showed slow electrophoretic mobility (band-shifting), recruitment to the cytoskeleton, and tyrosine phosphorylation at 165, 249, and 410 sites in both 48 h PO myocardium and 1 h RGD-stimulated cardiomyocytes. Adenoviral mediated expression of kinase inactive (negative) c-Src mutant with intact scaffold domains (KN-Src) in cardiomyocytes did not block the RGD stimulated changes in Cas. Furthermore, expression of KN-Src or kinase active c-Src mutant with intact scaffold function (A-Src) in two-dimensionally (2D) cultured cardiomyocytes was sufficient to cause Cas band-shifting, although tyrosine phosphorylation required A-Src. These data indicate that c-Src's adaptor function, but not its kinase function, is required for a serine/threonine specific phosphorylation(s) responsible for Cas band-shifting. To explore this possibility, Chinese hamster ovary cells that stably express Cas were infected with either β-gal or KN-Src adenoviruses and used for Cas immunoprecipitation combined with mass spectrometry analysis. In the KN-Src expressing cells, Cas showed phosphorylation at the serine-639 (human numbering) site. A polyclonal antibody raised against phospho-serine-639 detected Cas phosphorylation in 24-48 h PO myocardium. Our studies indicate that c-Src's adaptor function mediates serine-639 phosphorylation of Cas during integrin activation in PO myocardium. © 2015 Wiley Periodicals, Inc.

  12. Relationships of the tricuspid valve to the membranous ventricular septum in Down's syndrome without endocardial cushion defect: study of 28 specimens, 14 with a ventricular septal defect.

    Science.gov (United States)

    Rosenquist, G C; Sweeney, L J; McAllister, H A

    1975-10-01

    The commissure between the anterior and medial leaflets of the tricuspid valve is commonly absent in Down's syndrome without endocardial cushion defect (19 of 28 specimens). As a result, aneurysm of the membranous ventricular septum may develop (eight of 14 specimens with ventricular septal defect limited to the membranous ventricular septum) and the potential for left ventricle-to-right atrial communication is increased.

  13. Cardioprotective effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats.

    Science.gov (United States)

    Gao, Yan; Gao, Jianping; Chen, Changxun; Wang, Huilin; Guo, Juan; Wu, Rong

    2015-05-01

    The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation. Georg Thieme

  14. Histological assessment of myocardium in lethal ethanol intoxication.

    Science.gov (United States)

    Litwiejko-Pietryńczak, Elżbieta; Szkudlarek, Magdalena; Niemcunowicz-Janica, Anna; Namiot, Andrzej; Klim, Beata; Łaskowski, Paweł; Dzięcioł, Janusz

    2015-01-01

    The pathological mechanism of sudden death in healthy persons following incidental ethanol intoxication has not yet been fully elucidated and might be underlain by cardiogenic causes. Histological assessment of the myocardium in lethal ethanol intoxication. The analysis was based on a histological assessment of specimens of the myocardium obtained from the hearts of 30 deceased males within the age range 29-45 years. The material for the study was taken from the myocardium of the anterior wall of the left ventricle and interventricular septum of the heart. The fixation material was first examined according to the standard histological procedure and subsequently subjected to a morphometric examination, which assessed the number of cardiomyocytes, their area, circumference, and circular deviation. The examination showed an increase in the area and circumference of cardiomyocytes, as well as fragmentation and segmentation of cardiomyocytes with a significant enlargement of cell nuclei. Additionally, it revealed the presence of lymphocytic cells in several cases.Conclusions: The obtained findings indicate a harmful influence of alcohol on the myocardium.

  15. Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts.

    Science.gov (United States)

    Huang, Shangwei; Wu, Liqun; Huang, Jian; Panitchob, Nuttanont; Hu, Nan; Ranjan, Ravi; Dosdall, Derek J

    2017-01-01

    The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1-2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 μM). Pacing pulses were delivered directly to the His bundle. By using standard glass microelectrodes, action potentials duration (APD) from the His bundle and WM were obtained simultaneously over a wide range of stimulation cycle lengths (CL). The global F-test indicated that the two restitution curves of the His bundle and the WM are statistically significantly different (PHis bundle was significantly shorter than that of WM throughout the whole pacing course (PHis bundle vs. the WM were shorter for the His bundle (134.2±13.1ms vs. 148.3±13.3ms, PHis bundle than in WM (130.0±10.0 vs. 145.6±14.2ms, PHis bundle APD was significantly shorter than that of WM under both slow and rapid pacing rates, which suggest that there may be an excitable gap during VF and that the His bundle may conduct wavefronts from one bundle branch to the other at short cycle lengths and during VF.

  16. Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

    Science.gov (United States)

    Saraf, Rabya; Huang, Thomas; Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D; Sellke, Frank; Matyal, Robina

    2016-01-01

    Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

  17. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  18. Right ventricular function in children with bronchial asthma: a tissue Doppler echocardiographic study.

    Science.gov (United States)

    Shedeed, Soad A

    2010-10-01

    Asthma is the most common cause of respiratory disability among children. Patients with severe bronchial asthma can experience cor pulmonale later in life, but little is known about the function of the right ventricle early in the disease. This study aimed to investigate the right ventricular function in children with bronchial asthma as detected by tissue Doppler echocardiography. This case-control study compared 60 asthmatic children ages 5 to 15 years between attacks (study group) with 60 apparently healthy children (control group). All the children were subjected to full history-taking, complete physical examination, measurement of peak expiratory flow rate (PEFR), chest x-ray, electrocardiography (ECG), echocardiographic examination, and both conventional and tissue Doppler study. The results of the tissue Doppler study examining the right ventricular diastolic function showed that peak E' velocity (10.08 ± 2.8 cm/s), peak A' velocity (5.7 ± 2.5 cm/s), E'/A' ratio (1.77 ± 0.58 m/s), and isovolumetric relaxation time (IVRT) of the lateral tricuspid annulus (138.9 ± 30.7 m/s) among the asthmatic patients differed significantly from those among the control subjects (12.4 ± 2.3, 7.8 ± 2.1 cm/s; 1.58 ± 0.32, and 91.1 ± 32.6 m/s, respectively). In addition, the E' velocity and IVRT of the lateral tricuspid annulus were significantly different among the mild, moderate, and severe cases (P children were apparently normal, the tissue Doppler echocardiographic study showed right ventricular dysfunction that is positively correlated with the severity of asthma. These findings signify the diagnostic value of tissue Doppler echocardiography for the early detection and monitoring of such deleterious effects among asthmatic patients.

  19. Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

    Science.gov (United States)

    Drobnik, J; Tosik, D; Piera, L; Szczepanowska, A; Olczak, S; Zielinska, A; Liberski, P P; Ciosek, J

    2013-12-01

    Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 μg/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole.

  20. Quantification of left ventricular myocardial collagen system in children, young adults, and the elderly Cuantificación del sistema de colágeno del ventrículo izquierdo del miocardio en niños, adultos jóvenes y ancianos

    OpenAIRE

    Andrea Bogoslavsky Levy Mendes; Marcelo Ferro; Bruno Rodrigues; Monica Rodrigues de Souza; Rubens Correa Araujo; Romeu Rodrigues de Souza

    2012-01-01

    Studies on the collagen system of the human myocardium are still limited compared to those on small laboratory animals. The aim of this work was to observe the collagen tissue of the myocardium of the human heart as a function of age. The types of collagen, as well as the density of collagen tissue and the diameter of collagen fibrils, were examined. Fragments of the left ventricular wall from 15 hearts, 5 from children, 5 from young adults, and 5 from elderly individuals, were analyzed by us...

  1. High spatial resolution and temporally resolved T2* mapping of normal human myocardium at 7.0 Tesla: an ultrahigh field magnetic resonance feasibility study.

    Directory of Open Access Journals (Sweden)

    Fabian Hezel

    Full Text Available Myocardial tissue characterization using T(2(* relaxation mapping techniques is an emerging application of (preclinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T(2(* mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T(2(* imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T(2(* mapping. In phantom experiments single cardiac phase and dynamic (CINE gradient echo imaging techniques provided similar T(2(* maps. In vivo studies showed that the peak-to-peak B(0 difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T(2(* weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T(2(* values were found for anterior (T(2(* = 14.0 ms, anteroseptal (T(2(* = 17.2 ms and inferoseptal (T(2(* = 16.5 ms myocardial segments. Shorter T(2(* values were observed for inferior (T(2(* = 10.6 ms and inferolateral (T(2(* = 11.4 ms segments. A significant difference (p = 0.002 in T(2(* values was observed between end-diastole and end-systole with T(2(* changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T(2(* mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes.

  2. Autologous bone marrow cell implantation attenuates left ventricular remodeling and improves heart function in porcine myocardial infarction: an echocardiographic, six-month angiographic, and molecular-cellular study.

    Science.gov (United States)

    Leu, Steve; Sun, Cheuk-Kwan; Sheu, Jiunn-Jye; Chang, Li-Teh; Yuen, Chun-Man; Yen, Chia-Hung; Chiang, Chiang-Hua; Ko, Sheung-Fat; Pei, Sung-Nan; Chua, Sarah; Youssef, Ali A; Wu, Chiung-Jen; Yip, Hon-Kan

    2011-07-15

    We investigated the potential benefits and the underlying mechanisms of autologous bone marrow-derived mononuclear cell (BMDMNC) implantation in a porcine model of acute anterior wall myocardial infarction (AAWMI) by studying 6-month left ventricular (LV) function and LV remodeling. After being aspirated from the iliac crest and cultured for 1 week, BMDMNCs were implanted immediately after AAWMI induction through the left anterior descending artery ligation. Thirty male mini-pigs (16-18 kg) were equally divided into group 1 [AAWMI plus saline injection into infarct-ischemia area (IA)], group 2 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into non-IA), group 3 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into IA), group 4 (sham control plus 3.0 × 10⁷ BMDMNC transplantation into LV myocardium), and group 5 (normal control). By day 90, echocardiography demonstrated an increased LV end-diastolic and end-systolic dimensions but reduced LV ejection fraction (LVEF) in groups 1 and 2 than in other groups (all p infarct area, the number of small vessels and mRNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin (IL)-10, and peroxisome proliferator-activated receptor-γ coactivator-1α were lower, whereas the number of apoptotic nuclei, caspase-3, Bax, endothelin-1, IL-8, and matrix metalloproteinase was higher in groups 1 and 2 than in other groups (all p < 0.01). Autologous BMDMNC transplantation into IA rather non-IA improves LV function and reduces LV remodeling via eliciting a broad-spectrum of molecular-cellular defensive mechanisms. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

    Science.gov (United States)

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Hirsch, Alexander; van der Laan, Anja M; Delewi, Ronak; van der Vleuten, Pieter A; Tio, René A; Tijssen, Jan G P; Hofman, Mark B M; Piek, Jan J; Zijlstra, Felix; van Rossum, Albert C

    2014-07-01

    To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone. © RSNA, 2014.

  4. Natural history of arrhythmogenic right ventricular cardiomyopathy in the boxer dog: a prospective study.

    Science.gov (United States)

    Meurs, K M; Stern, J A; Reina-Doreste, Y; Spier, A W; Koplitz, S L; Baumwart, R D

    2014-01-01

    Boxer arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that may result in sudden death or heart failure. To prospectively study the natural history of Boxer ARVC. 72 dogs (49 ARVC, 23 controls). Boxers >1 year of age were recruited for annual reevaluation. CONTROLS were defined as being ≥6 years of age and having Dogs were genotyped for the striatin deletion when possible. Descriptive statistics were determined for age; VPC number; annual change in VPC number; and left ventricular (LV) echocardiographic dimensions. Survival time was calculated. median age of 7 years (range, 6-10); number of VPCs 12 (range, 4-32). Median time in study of 6 years (range, 2-9). Seventeen of 23 were genotyped (5 positive, 12 negative). ARVC: median age of diagnosis of 6 (range, 1-11). Median time in study 5 years (range, 3-8). A total of 33% were syncopal and 43/49 were genotyped (36 positive, 7 negative). Yearly change in VPCs was 46 (range, -7,699 to 33,524). Annual percentage change in LV dimensions was 0, and change in fractional shortening (FS%) was 2%. Two dogs had FS% dogs died suddenly, there was no difference in survival time between groups. ARVC median age of survival was 11 years, and for controls was 10 years. Arrhythmogenic right ventricular cardiomyopathy is a disease of middle age and frequently is associated with the striatin deletion. Syncope occurs in approximately 1/3 of affected dogs; systolic dysfunction is uncommon. The prognosis in many affected dogs is good. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  5. Pulse pressure, left ventricular function and cardiovascular events during antihypertensive treatment (the LIFE study)

    DEFF Research Database (Denmark)

    Gerdts, Eva; Franklin, Stanley; Rieck, Ashild

    2009-01-01

    Background. Pulse pressure (PP) has been related to risk of cardiovascular events in hypertension. However, less is known about modification of this risk marker during antihypertensive treatment in patients with left ventricular (LV) hypertrophy. Methods. Associations of in-treatment PP with LV......, Framingham risk score and study treatment allocation. Conclusion. During systematic antihypertensive treatment in hypertensive patients with electrocardiographic LV hypertrophy, lower in-treatment PP was associated with lower in-treatment LV function and cardiac output as well as higher rate...

  6. APLICACIONES CLÍNICAS DE LAS TÉCNICAS NUCLEARES EN EL ESTUDIO DEL SINCRONISMO VENTRICULAR / Clinical applications of nuclear techniques in the study of ventricular synchronism

    Directory of Open Access Journals (Sweden)

    Amalia Peix González

    2012-07-01

    Full Text Available ResumenTécnicas incruentas como la ecocardiografía, la resonancia magnética nuclear y los estudios de Medicina Nuclear (ventriculografía radioisotópica y gammagrafía de perfusión miocárdica con tomografía de emisión de fotón único, proporcionan información indirecta sobre el sincronismo ventricular cuando se utilizan parámetros de contractilidad mecánica. El análisis de fase de Fourier es un instrumento útil para el empleo de técnicas nucleares con este propósito y se ha aplicado, tanto en la ventriculografía radioisotópica como en la gammagrafía de perfusión. En este trabajo se presenta una revisión en el tiempo de los fundamentos y aplicaciones clínicas de las técnicas nucleares en el estudio del sincronismo ventricular. En la actualidad es la gammagrafía SPECT-gatillada, dentro de las técnicas nucleares, la más utilizada, por la posibilidad que ofrece de evaluar perfusión, función y sincronismo intraventricular en el mismo examen. / AbstractNoninvasive techniques such as echocardiography, nuclear magnetic resonance imaging and nuclear medicine studies (radionuclide ventriculography and myocardial perfusion scintigraphy with single photon emission tomography, provide indirect information about ventricular synchronism when parameters of mechanical contractility are used. The Fourier phase analysis is a useful tool for the use of nuclear techniques for this purpose, and has been applied in both radionuclide ventriculography and perfusion scintigraphy. A review in time of the basics and clinical applications of nuclear techniques in the study of ventricular synchronism is presented in this article. Nowadays, the gated-SPECT scintigraphy is the most common among nuclear techniques because it allows assessing perfusion, function, and intraventricular synchronism in the same test.

  7. Determinants of left ventricular mass in obesity; a cardiovascular magnetic resonance study

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    Clarke Kieran

    2009-04-01

    Full Text Available Abstract Background Obesity is linked to increased left ventricular mass, an independent predictor of mortality. As a result of this, understanding the determinants of left ventricular mass in the setting of obesity has both therapeutic and prognostic implications. Using cardiovascular magnetic resonance our goal was to elucidate the main predictors of left ventricular mass in severely obese subjects free of additional cardiovascular risk factors. Methods 38 obese (BMI 37.8 ± 6.9 kg/m2 and 16 normal weight controls subjects, (BMI 21.7 ± 1.8 kg/m2, all without cardiovascular risk factors, underwent cardiovascular magnetic resonance imaging to assess left ventricular mass, left ventricular volumes and visceral fat mass. Left ventricular mass was then compared to serum and anthropometric markers of obesity linked to left ventricular mass, i.e. height, age, blood pressure, total fat mass, visceral fat mass, lean mass, serum leptin and fasting insulin level. Results As expected, obesity was associated with significantly increased left ventricular mass (126 ± 27 vs 90 ± 20 g; p 2 = 0.77. Conclusion The left ventricular hypertrophic response to obesity in the absence of additional cardiovascular risk factors is mainly attributable to increases in lean body mass, LV stroke volume and visceral fat mass. In view of the well documented link between obesity, left ventricular hypertrophy and mortality, these findings have potentially important prognostic and therapeutic implications for primary and secondary prevention.

  8. Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study

    Energy Technology Data Exchange (ETDEWEB)

    Clayton, Richard H; Holden, Arun V [School of Biomedical Sciences, University of Leeds, Woodhouse Lane, Leeds (United Kingdom)

    2003-01-07

    Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.

  9. Transmyocardial laser revascularization fails to prevent left ventricular functional deterioration and aneurysm formation after acute myocardial infarction in sheep.

    Science.gov (United States)

    Malekan, R; Kelley, S T; Suzuki, Y; Reynolds, C; Plappert, T; Sutton, M S; Edmunds, L H; Bridges, C R

    1998-11-01

    Transmyocardial laser revascularization is an investigational technique for revascularizing ischemic myocardium in patients with inoperable coronary arterial disease. This study tests the hypothesis that laser revascularization prevents left ventricular functional deterioration and aneurysm formation after acute anteroapical myocardial infarction. An ultrasonic ascending aortic flow probe and snares around the distal left anterior descending and second diagonal coronary arteries were placed in 26 Dorsett hybrid sheep. Ten to 14 days later, snared arteries were occluded to produce an anteroapical infarction of 23% of left ventricular mass. Before infarction 14 animals had 34 +/- 4 transmyocardial perforations in the area of the anticipated infarction made with a carbon dioxide laser. Twelve animals served as controls. Hemodynamic measurements and transdiaphragmatic quantitative echocardiograms were obtained before, immediately after, and 2, 5, and 8 weeks after infarction. Eighteen sheep completed the protocol. All animals had large anteroapical left ventricular aneurysms with massive ventricular enlargement. Immediately after infarction the anterior wall became thinner and dyskinetic in all sheep. At 8 weeks aneurysmal size and shape were indistinguishable between groups. Two days after infarction, laser holes were filled with fibrin. At 5 and 8 weeks the infarct consisted of dense collagen, fibroblasts, scattered calcifications, myocyte fragments, neutrophils, macrophages, and no laser holes. There were no significant differences at any time between groups for cardiac pressures or output, ventricular volumes, ejection fraction, stroke work, and the stroke work-left ventricular end-diastolic pressure index. Transmyocardial laser perforations do not revascularize acute myocardial infarction in sheep.

  10. Acute Effects of Hemodialysis on Left and Right Ventricular Function: A Doppler Tissue Imaging Study

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    Tansel Erol

    2012-08-01

    Full Text Available Purpose: Doppler tissue imaging (DTI allows noninvasive assessment of both left ventricular (LV and right ventricular (RV function. The aim of this study was to evaluate the effect of hemodialysis (HD on LV and RV function using DTI. Method: Our study group included 30 patients on chronic HD program (mean age 45 15 years. Myocardial (Sm, Em, Am and annular velocities (Ea, Aa were measured in several cardiac territories before and after HD. Results: After HD, Ea significantly reduced from 10.8 3.4 cm/s to 9.6 2.4 cm/s (p = 0.029. Patients exhibited a lower Em following HD in all measured territories. Em/Am ratio was also reduced for each LV wall investigated after HD in all measured territories. At the RV segments, Sm, Em, and Am decreased significantly in all measured territories. Em of the anterior wall was positively related to ultrafiltration volume (r = 0.25, p = 0.006, whereas the decrease of Sm of RV basal segment correlated with a decrease of diastolic blood pressure (r = 0.23, p < 0.01. Conclusion: Our data indicate that a single HD session is associated with acute changes of systolic and diastolic parameters of LV and RV. [Cukurova Med J 2012; 37(4.000: 215-222

  11. Reduced right ventricular diameter during cardiac arrest caused by tension pneumothorax - a porcine ultrasound study.

    Science.gov (United States)

    Caap, P; Aagaard, R; Sloth, E; Løfgren, B; Granfeldt, A

    2017-08-01

    Advanced life support (ALS) guidelines recommend ultrasound to identify reversible causes of cardiac arrest. Right ventricular (RV) dilatation during cardiac arrest is commonly interpreted as a sign of pulmonary embolism. The RV is thus a focus of clinical ultrasound examination. Importantly, in animal studies ventricular fibrillation and hypoxia results in RV dilatation. Tension pneumothorax (tPTX) is another reversible cause of cardiac arrest, however, the impact on RV diameter remains unknown. To investigate RV diameter evaluated by ultrasound in cardiac arrest caused by tPTX or hypoxia. Pigs were randomized to cardiac arrest by either tPTX (n = 9) or hypoxia (n = 9) and subsequently resuscitated. Tension pneumothorax was induced by injection of air into the pleural cavity. Hypoxia was induced by reducing tidal volume. Ultrasound images of the RV were obtained throughout the study. Tension pneumothorax was decompressed after the seventh rhythm analysis. The primary endpoint was RV diameter after the third rhythm analysis. At cardiac arrest the RV diameter was 17 mm (95% CI: 13; 21) in the tPTX group and 36 mm (95% CI: 33; 40) in the hypoxia group (P cardiac arrest caused by tPTX when compared with hypoxia. The difference disappears after tPTX decompression. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. [Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients].

    Science.gov (United States)

    Berrut, G; Chameau, A M; Bouhanick, B; Page, J D; Hallab, M; Richard, C; Girault, A; Fressinaud, P; Marre, M

    To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi-squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria.

  13. A novel design of ventricular assist device: an in vitro feasibility study.

    Science.gov (United States)

    Boccaccio, Antonio; Carbone, Carmine; Galietti, Umberto; Mastropasqua, Filippo; Pappalettere, Carmine

    2012-11-01

    Left ventricular assist devices (LVADs) work as a bypass between the left ventricular apex and the ascending aorta. The surgical procedure for their insertion requires the opening of the cardiac cavities and the dissection of the great vessels, the blood is constrained to flow through the device components and the risk can be run of thrombogenesis, haemolysis and infections. A possible strategy to overcome this limitation consists in utilizing external systems that assist the heart in its contraction from the outside without directly transporting the blood. In this study we conduct the feasibility analysis of a novel external LVAD design that does not require the opening of the cardiac cavities and the dissection of the great vessels and that allows the removal procedure to be easily achieved. The device, including a stepper motor, three metallic wires and three elastic elements, works alternatively between a contraction condition where it induces an elastic compulsion on the heart and a release condition where it elastically releases the organ. The values of force acting on the wires and the values of current supplied to the motor were measured and utilized for a preliminary study design. The experimental measurements demonstrated the feasibility of the system.

  14. Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.

    Science.gov (United States)

    Weber, Thomas; Wassertheurer, Siegfried; Schmidt-Trucksäss, Arno; Rodilla, Enrique; Ablasser, Cornelia; Jankowski, Piotr; Lorenza Muiesan, Maria; Giannattasio, Cristina; Mang, Claudia; Wilkinson, Ian; Kellermair, Jörg; Hametner, Bernhard; Pascual, Jose Maria; Zweiker, Robert; Czarnecka, Danuta; Paini, Anna; Salvetti, Massimo; Maloberti, Alessandro; McEniery, Carmel

    2017-12-01

    We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m2, and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively (P=0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively (P=0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732. © 2017 American Heart Association, Inc.

  15. Evolution of Ventricular Energetics in the Different Stages of Palliation of Hypoplastic Left Heart Syndrome: A Retrospective Clinical Study.

    Science.gov (United States)

    Di Molfetta, A; Iacobelli, R; Guccione, P; Di Chiara, L; Rocchi, M; Cobianchi Belisari, F; Campanale, M; Gagliardi, M G; Filippelli, S; Ferrari, G; Amodeo, A

    2017-12-01

    Hyperplastic left heart syndrome (HLHS) patients are palliated by creating a Fontan-type circulation passing from different surgical stages. The aim of this work is to describe the evolution of ventricular energetics parameters in HLHS patients during the different stages of palliation including the hybrid, the Norwood, the bidirectional Glenn (BDG), and the Fontan procedures. We conducted a retrospective clinical study enrolling all HLHS patients surgically treated with hybrid procedure and/or Norwood and/or BDG and/or Fontan operation from 2011 to 2016 collecting echocardiographic and hemodynamic data. Measured data were used to calculate energetic variables such as ventricular elastances, external and internal work, ventriculo-arterial coupling and cardiac mechanical efficiency. From 2010 to 2016, a total of 29 HLHS patients undergoing cardiac catheterization after hybrid (n = 7) or Norwood (n = 6) or Glenn (n = 8) or Fontan (n = 8) procedure were retrospectively enrolled. Ventricular volumes were significantly higher in the Norwood circulation than in the hybrid circulation (p = 0.03) with a progressive decrement from the first stage to the Fontan completion. Ventricular elastances were lower in the Norwood circulation than in the hybrid circulation and progressively increased passing from the first stage to the Fontan completion. The arterial elastance and Rtot increased in the Fontan circulation. The ventricular work progressively increased. Finally, the ventricular efficiency improves passing from the first to the last stage of palliation. The use of ventricular energetic parameters could lead to a more complete evaluation of such complex patients to better understand their adaptation to different pathophysiological conditions.

  16. Extracorporeal life support with left ventricular decompression-improved survival in severe cardiogenic shock: results from a retrospective study.

    Science.gov (United States)

    Schmack, Bastian; Seppelt, Philipp; Weymann, Alexander; Alt, Christina; Farag, Mina; Arif, Rawa; Doesch, Andreas O; Raake, Philip W; Kallenbach, Klaus; Mansur, Ashham; Popov, Aron-Frederik; Karck, Matthias; Ruhparwar, Arjang

    2017-01-01

    Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression. Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial. Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival. ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.

  17. Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Chinali, M.; Simone, G. de; Wachtell, K.

    2008-01-01

    with larger left ventricular diameter and higher left ventricular mass index (both P hypertrophy was greater (84 vs. 64%; P cardiac output......In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial......, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P hypertrophy, but normal left ventricular chamber systolic function with increased...

  18. Mitotically inactivated embryonic stem cells can be used as an in vivo feeder layer to nurse damaged myocardium after acute myocardial infarction: a preclinical study.

    Science.gov (United States)

    Burt, Richard K; Chen, You-hong; Verda, Larissa; Lucena, Carolina; Navale, Shankararao; Johnson, Jesse; Han, Xiaoqiang; Lomasney, Jon; Baker, Jessa M; Ngai, Ka-Leung; Kino, Aya; Carr, James; Kajstura, Jan; Anversa, Piero

    2012-10-26

    Various types of viable stem cells have been reported to result in modest improvement in cardiac function after acute myocardial infarction. The mechanisms for improvement from different stem cell populations remain unknown. To determine whether irradiated (nonviable) embryonic stem cells (iESCs) improve postischemic cardiac function without adverse consequences. After coronary artery ligation-induced cardiac infarction, either conditioned media or male murine or male human iESCs were injected into the penumbra of ischemic myocardial tissue of female mice or female rhesus macaque monkeys, respectively. Murine and human iESCs, despite irradiation doses that prevented proliferation and induced cell death, significantly improved cardiac function and decreased infarct size compared with untreated or media-treated controls. Fluorescent in situ hybridization of the Y chromosome revealed disappearance of iESCs within the myocardium, whereas 5-bromo-2'-deoxyuridine assays revealed de novo in vivo cardiomyocyte DNA synthesis. Microarray gene expression profiling demonstrated an early increase in metabolism, DNA proliferation, and chromatin remodeling pathways, and a decrease in fibrosis and inflammatory gene expression compared with media-treated controls. As a result of irradiation before injection, ex vivo and in vivo iESC existence is transient, yet iESCs provide a significant improvement in cardiac function after acute myocardial infarction. The mechanism(s) of action of iESCs seems to be related to cell-cell exchange, paracrine factors, and a scaffolding effect between iESCs and neighboring host cardiomyocytes.

  19. Focal Left Atrial Tachycardia in a Patient with Left Ventricular Noncompaction

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    Shailendra Singh

    2013-01-01

    Full Text Available Left ventricular noncompaction (LVNC is a rare disease caused by intrauterine failure of the myocardium to compact. The major clinical manifestations of LVNC include heart failure, ventricular tachyarrhythmia, thromboembolic event, and sudden deaths. Atrial arrhythmia usually seen is atrial fibrillation. We report a rare case of focal left atrial tachycardia in an 18-year-old patient who presented for evaluation of persistent tachycardia. Transthoracic echocardiogram showed severe systolic dysfunction and evidence of noncompaction of the left ventricle. A detailed review of ECG revealed the possibility of ectopic atrial tachycardia, most likely originating from the left side. Electrophysiology study showed sustained atrial tachycardia originating on the ridge anterior to the left sided pulmonary veins. A successful radiofrequency catheter ablation was performed at this site without any complications.

  20. Study of left ventricular diastolic dysfunction in recently diagnosed hypertensives in Central Nepal

    Directory of Open Access Journals (Sweden)

    Shankar Laudari

    2016-03-01

    Full Text Available CORRECTION: The conclusion on the PDF of this article was replaced on 17th April 2016. The corrected PDF is now available by clicking on the link below.Background & Objectives: Ectopic Left ventricular diastolic dysfunction is now well established as a cause of left sided heart failure and as a powerful predictor of cardiovascular events. It is attributed mostly to systemic hypertension. The objective of the study was to determine the prevalence of left ventricular diastolic dysfunction in recently diagnosed hypertensives in Nepalese population using echocardiography. Materials & Methods: Two-dimensional echocardiography was performed on 120 newly diagnosed patients of systemic hypertension. Transmitral Doppler indexes of diastolic function, Valsalva maneuver applied to the same mitral inflow pattern, pulsed tissue Doppler of the mitral annulus, deceleration time, isovolumic relaxation time and pulmonary venous flow pattern.Results: The age of the patients in our study ranged from 20 to 84 years with mean age of 50years±14.13 years (standard deviation and male:female ratio being 1.35:1. Hypertensive patients were highest in age group 45-64 years followed by 25-44 years in both the genders. Majority of the patients had stage 1 hypertension (44.16% followed by stage 2 HTN in 34.17% and pre-hypertension in 21.67%. The majority of the patients in our study had Grade 1 LVDD (66.67%, 10.83% patients had Grade II LVDD, only 2.50% had non-restrictive Grade III LVDD and none had LVDD-IV. Stage II hypertensives had more LVDD(I+II+III: 39/41-95.12% than stage I hypertensives(39/53-73.58% and pre-hypertensives (8/26-30.77%. The association between stages of systemic HTN and LVDD was found to be highly statistically significant (p=0.002. Conclusion: Our study showed that left ventricular diastolic dysfunction is a common entity in Nepalese population with systemic hypertension.JCMS Nepal. 2016;12(1:14-18.

  1. Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol

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    Botti Fiorenzo

    2002-09-01

    Full Text Available Abstract Background Experimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD. In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ. In the hypothesis that chronic inflammation and increased collagen metabolism are reflected also in the systemic circulation, we aimed this study to evaluate the effects on left ventricular wall structure by assessing splancnic and systemic collagen metabolism (procollagen III assay, deposition (ultrasonic tissue characterization, and cardiac function (echocardiography in patients with different long standing history of IBD, before and after surgery. Methods Thirty patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis, submitted to surgery will be enrolled in the study in a double blind fashion. They will be studied before the surgical operation and 6, 12 months after surgery. A control group of 15 healthy age and gender-matched subjects will also be studied. At each interval blood samples will be collected in order to assess the collagen metabolism; a transthoracic echocardiogram will be recorded for the subsequent determination of cardiac function and collagen deposition. Discussion From this study protocol we expect additional information about the association between IBD and cardiovascular disorders; in particular to address the question if chronic inflammation, through the altered collagen metabolism, could affect left ventricular structure and function in a manner directly related to the estimated duration of the disease.

  2. First Reported Case of Arrhythmogenic Right Ventricular Cardiomyopathy in Oman

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    Hatim Al Lawati

    2017-07-01

    Full Text Available Arrhythmogenic right ventricular cardiomyopathy (ARVC is a rare genetic disorder characterized by fatty degeneration of the right ventricular myocardium with variable involvement of the left ventricle. The condition is associated with exercise-mediated ventricular tachycardia and is one of the recognized causes of sudden cardiac death in the young and in athletes. Here, we report the first confirmed case of ARVC in Oman and present its electrocardiographic, echocardiographic features, and radiological findings on gated, contrast-enhanced cardiac computed tomography. Our patient was a 22-year-old male who had presented to our hospital for evaluation and investigation of syncope and symptomatic palpitations.

  3. Características morfológicas do miocárdio ventricular de Tambaqui (Colossoma macropomun; Characidae, Cuvier, 1818

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    Karina Simões

    2002-01-01

    Full Text Available The neotropical teleost fish Colossoma macropomun an active swimming species showed cardiac ventricle with pyramidal shape and myocardium with mixed structure. The myocardium presented an outer compact layer and an inner spongy layer whose particular bilaminar structure hitherto has been correlated to swimmer habit as well as to ventricular shape.

  4. O miocárdio na tetralogia de Fallot: estudo histológico e morfométrico El miocardio en la tetralogía de Fallot: estudio histológico y morfométrico The myocardium in tetralogy of Fallot: a histological and morphometric study

    Directory of Open Access Journals (Sweden)

    Maria Cecília Knoll Farah

    2009-03-01

    ventriculares para estudios morfométricos.BACKGROUND: Patients with Tetralogy of Fallot frequently develop ventricular dysfunction in the postoperative period. The histological basis of this functional alteration has been scarcely studied. OBJECTIVE: To evaluate myocardial remodeling in anatomical specimens, comparing the subepicardial and subendocardial regions, especially because the subendocardial region is easily approached by means of endomyocardial biopsy. METHODS: Transmural sections of myocardium from the right ventricular (RV inflow tract, anterior wall and infundibulum, and from the left ventricular (LV free wall were evaluated regarding the degree of cardiomyocyte hypertrophy, vascularization and interstitial fibrosis were analyzed. RESULTS: The mean diameter of subendocardial cardiomyocytes is similar to that of subepicardial cardiomyocytes in all regions, except for the RV infundibulum, in which subendocardial cardiomyocytes are significantly larger in relation to those of the subepicardium (p=0.007. The amount of interstitial collagen is in the upper limits of normal and was similar in the subendocardial layers in comparison with the subpericardial layer of each region; however, it was greater in the inflow tract and RV anterior wall than in the LV lateral wall. The numerical density of subendocardial capillaries was similar to that of the subepicardium and was lower than the mean minus two standard deviations of normal in all regions and layers, except for the infundibulum, in which the subepicardium showed normal values and the subendocardium showed values lower than the mean minus two standard deviations. CONCLUSION: The postnatal myocardial changes in Tetralogy of Fallot are homogeneously distributed in the subepicardial and subendocardial halves of the ventricular walls, except for the infundibulum, which has peculiar remodeling characteristics and, therefore, is not representative of the other ventricular regions and layers for morphometric studies.

  5. Home versus office blood pressure: longitudinal relations with left ventricular hypertrophy: the Finn-Home study.

    Science.gov (United States)

    Sivén, Sam S E; Niiranen, Teemu J; Langén, Ville L J; Puukka, Pauli J; Kantola, Ilkka M; Jula, Antti M

    2017-02-01

    Electrocardiographically assessed left-ventricular hypertrophy (ECG-LVH) is a particularly high-risk phenomenon that is a part of every hypertensive patient's initial work-up. Several cross-sectional studies have demonstrated that home blood pressure (BP) has a stronger relation to LVH than office BP. However, longitudinal evidence on the association between home BP and target organ damage is scarce to nonexistent. We studied in a sample of 615 community-dwelling participants (mean age at baseline 53.7 ± 7.2, 58% women) whether change in home BP is more strongly associated with change in ECG-LVH than change in office BP over an 11-year follow-up. Pearson's correlation coefficients between changes in home/office SBP and changes in Sokolow-Lyon index, Cornell voltage, Cornell product and R wave amplitude in aVL were 0.21/0.18, 0.28/0.17, 0.25/0.16, and 0.32/0.20, respectively (asterisk indicates P home/office DBP and change in the aforementioned ECG-LVH indexes, the correlations were 0.12/0.12, 0.20/0.15, 0.16/0.12, and 0.28/0.19. Multivariable-adjusted regression modelling provided similar results. No clinically significant increase in correlations between home BP and ECG-LVH indexes occurred after the fourth day of home BP measurement. Our study demonstrates for the first time the superiority of home BP over office BP in the follow-up of left ventricular mass. The results of this and previous studies underline the importance of using out-of-office BP measurements as the primary method for assessing blood pressure levels.

  6. Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model.

    Science.gov (United States)

    Kudlicka, Jaroslav; Mlcek, Mikulas; Belohlavek, Jan; Hala, Pavel; Lacko, Stanislav; Janak, David; Havranek, Stepan; Malik, Jan; Janota, Tomas; Ostadal, Petr; Neuzil, Petr; Kittnar, Otomar

    2015-02-22

    Mild therapeutic hypothermia (MTH) is being used after cardiac arrest for its expected improvement in neurological outcome. Safety of MTH concerning inducibility of malignant arrhythmias has not been satisfactorily demonstrated. This study compares inducibility of ventricular fibrillation (VF) before and after induction of MTH in a whole body swine model and evaluates possible interaction with changing potassium plasma levels. The extracorporeal cooling was introduced in fully anesthetized swine (n = 6) to provide MTH. Inducibility of VF was studied by programmed ventricular stimulation three times in each animal under the following: during normothermia (NT), after reaching the core temperature of 32°C (HT) and after another 60 minutes of stable hypothermia (HT60). Inducibility of VF, effective refractory period of the ventricles (ERP), QTc interval and potassium plasma levels were measured. Starting at normothermia of 38.7 (IQR 38.2; 39.8)°C, HT was achieved within 54 (39; 59) minutes and the core temperature was further maintained constant. Overall, the inducibility of VF was 100% (18/18 attempts) at NT, 83% (15/18) after reaching HT (P = 0.23) and 39% (7/18) at HT60 (P = 0.0001) using the same protocol. Similarly, ERP prolonged from 140 (130; 150) ms at NT to 206 (190; 220) ms when reaching HT (P < 0.001) and remained 206 (193; 220) ms at HT60. QTc interval was inversely proportional to the core temperature and extended from 376 (362; 395) at NT to 570 (545; 599) ms at HT. Potassium plasma level changed spontaneously: decreased during cooling from 4.1 (3.9; 4.8) to 3.7 (3.4; 4.1) mmol/L at HT (P < 0.01), then began to increase and returned to baseline level at HT60 (4.6 (4.4; 5.0) mmol/L, P = NS). According to our swine model, MTH does not increase the risk of VF induction by ventricular pacing in healthy hearts. Moreover, when combined with normokalemia, MTH exerts an antiarrhythmic effect despite prolonged QTc interval.

  7. Characteristics of left ventricular hypertrophy estimated by MIBG and BMIPP cardiac scintigraphy in patients undergoing peritoneal dialysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hiroshige; Oda, Hiroshi; Ohno, Michiya; Watanabe, Sachirow; Kotoo, Yasunori; Matsuno, Yukihiko [Gifu Prefectural Hospital (Japan)

    2002-12-01

    Left ventricular hypertrophy (LVH) has been reported as a major factor in morbidity and mortality in chronic dialysis patients. However, cardiovascular mortality in peritoneal dialysis (PD) patients with LVH is substantially similar to that in hemodialysis (HD) patients. The present study sought to study whether sympathetic nerve activity and fatty acid metabolism of the myocardium estimated by {sup 123}I metaiodobenzylguanidine (MIBG) and {sup 123}I {beta}-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy are impaired or not in PD patients with LVH. The underlying disease of 45 PD patients enrolled in this study was chronic glomerulonephritis in all cases. Serum levels of natriuretic peptides (arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP)) and free carnitine and MIBG, BMIPP myocardial scintigraphy and 2-dimensional echocardiography were measured in these 45 PD patients. The following results were obtained. The prevalence of increased left ventricular mass index (LVMI) was 84.4%. LVMI correlated with age, and serum levels of ANP and BNP, and inversely correlated with a heart-to-mediastinum ratio (H/M) estimated by MIBG and BMIPP myocardial scintigraphy. Percentages of the normal image of MIBG and BMIPP measured with a single photon emission computed tomography (SPECT) were 37.8% and 62.2%, respectively. The PD patients showing the diffuse defect of MIBG or BMIPP imaging had the decrease in left ventricular ejection fraction (LVEF). Especially, the serum level of free carnitine was reduced in the PD patients with diffuse defect of BMIPP SPECT. From these results, we concluded that PD patients with LVH showed impaired sympathetic nerve activity and fatty acid metabolism of the myocardium. Metabolic and functional disturbances of the myocardium may influence mortality in PD patients. (author)

  8. Fused Segmentation of Geometric Models for Myocardium and Coronary Artery via Medial Axis

    OpenAIRE

    Chaa, Jehyun; Ryub, Joonghyun; Choi, Jin-Ho; Kim, Deok-Soo

    2017-01-01

    Coronary arteries and their branches supply blood to myocardium. The obstruction of coronary arteries results in significant loss of myocardium, called acute myocardial infarction, and the number one cause of death globally. Hence, quantification of the regional amount of heart muscle subtended by obstructed coronary arteries is of critical value in clinical medicine. However, the conventional methods are inaccurate and frequently disagree with clinical practices. This study proposes a novel ...

  9. The myocardium functional reserve indicators in junior children with recurrent acute upper respiratory tract infection

    Directory of Open Access Journals (Sweden)

    L.S. Ovcharenko

    2017-02-01

    Full Text Available Background. The problem of early diagnosis of cardiovascular diseases in children is relevant throughout the world and in Ukraine, as in childhood the health and quality of life of an adult are formed. The psychoemotional stress in junior children as well as increasingly complicating school curriculum, information overload with electronic gadgets, increased frequency of colds in children cause physical inactivity. In addition, infectious agents have a toxic effect on the myocardium, altering its functional state. All these together adversely affect the formation and development of the cardiovascular and respiratory systems of children. The aim was to study the functional reserve of the myocardium in junior children, depending on the frequency of upper respiratory tract infection (URTI. Materials and methods. The study examined 1109 children aged 6 to 9 years old. The URTI incidence was analyzed depending on the age. In the study, the children were divided into two groups. Group 1 consisted of the children with URTI — 210. Group 2 involved the children with occasional URTI — 899. Results. Among 210 surveyed children with upper respiratory infections 171 schoolboys (81.4 % had reduced functional reserve of the myocardium, which is consistent with findings from other studies. In children aged 7 and 9 years old, the number of reduced functional reserve of the myocardium varies from 70 to 82 % in seven-year children, among the schoolboys aged 6 and 8 years old the incidence of reduced functional reserve of the myocardium increased from 83 to 100 % in six-year children. Conclusions. Children with URTI have a reduced functional reserve of the myocardium. Children with episodic URTI have higher rates of functional reserve of the myocardium, therefore reducing the incidence of URTI will lead to the improvement of the myocardium functional state.

  10. Isometric relaxation of rat myocardium at end-systolic fiber length.

    Science.gov (United States)

    Wiegner, A W; Bing, S H

    1978-12-01

    In a "physiologically sequenced" contraction (PSC), which loads the isolated muscle preparation in a manner which approximates that of the intact heart, isometric relaxation precedes isotonic relaxation and occurs at minimum ("end-systolic") length. We studied the effects of inital muscle length, load, temperature, calcium, and isoproterenol on the isometric relaxation phase of physiologically sequenced contractions to define the determinants of the rate of isometric relaxation of rat left ventricular myocardium. At the baseline temperature (28 degrees C), relaxation was found to be nonexponential, and the maximum rate of decline of force (-dF/dtmax) was used to evaluate changes in relaxation. Three factors, shortening, end-systolic length, and total load, were examined as possible mechanical determinants of -dF/dtmax. We found that -dF/dtmax is linearly related to end-systolic muscle length for lengths below 94% of Lmax; -dF/dtmax is also strongly related to total load for lightly loaded contractions, but peaks at loads of approximately 80% of peak developed force and declines thereafter. Shortening is poorly correlated with -dF/dtmax. The slope of the linear portion of the relation between -dF/dtmax and end-systolic length appears to be independent of muscle-loading conditions and sensitive to factors known to alter relaxation.

  11. [Structural and functional changes of myocardium in Chernobyl disaster clean-up workers with atrial fibrillation].

    Science.gov (United States)

    Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A

    2011-01-01

    Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.

  12. Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study

    DEFF Research Database (Denmark)

    Gerdts, E; Okin, P M; Omvik, P

    2009-01-01

    BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual...... echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did...... shortening (both phypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment....

  13. Nationwide (Denmark) Study of Symptoms Preceding Sudden Death due to Arrhythmogenic Right Ventricular Cardiomyopathy

    DEFF Research Database (Denmark)

    Sadjadieh, Golnaz; Jabbari, Reza; Risgaard, Bjarke

    2014-01-01

    In this study, we investigated medical history and symptoms before death in all subjects aged 1 to 35 years who died a sudden cardiac death (SCD) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in Denmark in the years 2000 to 2006. All deaths (n=6,629) in subjects aged 1 to 35 years...... in Denmark in the period 2000 to 2006 were included. A total of 16 cases of SCD due to ARVC were identified based on histopathologic examination. Information on medical history was retrieved from The National Patient Registry, general practitioners, and hospitals. Symptoms before death were compared with 2...... and 7 of them sought medical attention. None were diagnosed with ARVC before death. Only 1 patient in the healthy control group and 31 of the 39 patients with CAD experienced cardiac symptoms before death. A total of 6 patients of the 16 with ARVC died during strenuous physical activity and 4...

  14. [A study of ventricular repolarization duration variability and dependence of RTm/RR].

    Science.gov (United States)

    Pan, J; Zhu, Y; Pan, C; Zhou, L

    2000-03-01

    As an important electrophysiological parameter that reflects cardiac depolarization and repolarization process, ventricular repolarization duration has been drawing growing attention. It is influenced by several physiological and pathological factors and associated with several cardiac diseases. We studied repolarization duration variability (RDV) and dependence of RTm/RR among normal subjects of different age-groups, as well as between normal subjects and subjects with cardiac diseases. It was found that RDV and dependence of RTm/RR are related to age. There are significant differences in the slope of RTm/RR, coherence, CV ratio and RDV between normal subjects and subjects with cardiac diseases. The RDV and dependence of RTm/RR can be employed in providing a more useful evaluation of cardiac disease and function in clinical care.

  15. Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Xiaorong Li

    Full Text Available Induced pluripotent stem (iPS cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI. We hypothesize that porcine iPS (piPS cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively. Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p = 0.04 but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p = 0.02. The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01. PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.

  16. Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

    Science.gov (United States)

    Choo, Eun Ho; Lee, Jun-Ho; Park, Eun-Hye; Park, Hyo Eun; Jung, Nam-Chul; Kim, Tae-Hoon; Koh, Yoon-Seok; Kim, Eunmin; Seung, Ki-Bae; Park, Cheongsoo; Hong, Kwan-Soo; Kang, Kwonyoon; Song, Jie-Young; Seo, Han Geuk; Lim, Dae-Seog; Chang, Kiyuk

    2017-04-11

    Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair. © 2017 American Heart Association, Inc.

  17. Effect of Age on Left Ventricular Global Dyssynchrony in Asymptomatic Individuals: A Population Study.

    Science.gov (United States)

    Vancheri, Federico; Vancheri, Sergio; Henein, Michael Y

    2016-07-01

    Left ventricular (LV) segmental dyssynchrony is common in patients with heart failure or myocardial activation abnormalities and is associated with increased cardiovascular risk. Total isovolumic time (t-IVT) and Tei index are sensitive indexes of global ventricular dyssynchrony. The aim of this study was to investigate the effect of age on t-IVT and Tei index. We evaluated 410 individuals with no evidence for coronary heart disease or activation abnormalities. T-IVT was calculated as 60 - (total ejection time + total filling time) and Tei index as t-IVT/total ejection time. The relationship between age, LV systolic and diastolic function parameters as well as t-IVT and Tei index was studied. Ejection fraction and stroke volume did not change with age, whereas early diastolic filling velocity fell and atrial systolic velocity increased, reducing the E/A ratio. Isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) lengthened. With every 10 years of age, total LV ejection time shortened by 1.5 sec/min and total filling time by 2.1 sec/min. T-IVT and Tei index increased with age and strongly correlated with IVCT and E/A, but not with ejection fraction or QRS duration. Normal aging is associated with worsening of LV global dyssynchrony shown by prolongation of isovolumic times resulting in shortening of filling and ejection times. Age also affects diastolic function as shown by E/A but not systolic function parameters, ejection fraction or stroke volume. Worsening of global dyssynchrony correlates with that of diastolic function but not with QRS duration. © 2016, Wiley Periodicals, Inc.

  18. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism.

    Science.gov (United States)

    Aquilani, Roberto; La Rovere, Maria Teresa; Corbellini, Daniela; Pasini, Evasio; Verri, Manuela; Barbieri, Annalisa; Condino, Anna Maria; Boschi, Federica

    2017-11-15

    The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF), and relate them to left ventricular function and disease severity. Amino acids (AAs) play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA) class II to IV) were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI), protein-, fat-, carbohydrate-intake, resting energy expenditure (REE), total daily energy expenditure (REE × 1.3), and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF) severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001) and cardiac index (r = 0.4243; p = 0.0028). The value of arterial aspartic acid (µmol/L) multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076). All NYHA groups had adequate protein intake (≥1.1 g/kg/day) and inadequate calorie intake (KcalI < REE × 1.3) was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  19. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Aquilani

    2017-11-01

    Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  20. DDDR pacing results in left ventricular asynchrony with preservation of ejection fraction and NT-proBNP: a prospective study in sick sinus syndrome and normal ventricular function.

    Science.gov (United States)

    Psychari, Stavroula N; Apostolou, Thomas S; Iliodromitis, Efstathios K; Charalampopoulos, Athanasios; Kremastinos, Dimitrios T

    2010-10-08

    Desynchronization induced by right ventricular pacing may increase the risk for heart failure. We aimed to compare left ventricular (LV) function, synchrony and left atrial size along with NT-proBNP levels, in 2 different modes of pacing: AAIR versus DDDR. This was a prospective study of 60 patients with sick sinus syndrome, preserved LV function and normal atrioventricular conduction. Each pacing mode lasted at least 2 months, in every patient, after which period every patient was switched to the alternate pacing mode. Intraventricular asychrony was assessed by: 1) M-Mode septal-to-posterior wall motion delay (SPWMD), and 2) Tissue Doppler imaging (TDI) septal to lateral delay. NT-proBNP was measured at the end of each pacing mode. LV ejection fraction and left atrial diameter were not different in the 2 pacing modes, although asynchrony was induced in the DDDR arm (pAAIR mode (p=0.003, F=9.64). The NT-proBNP was inversely correlated to LV ejection fraction in the DDDR mode (p=0.0001, R=-0.75), whilst it was significantly correlated to the TDI septal-lateral delay and SPWMD (p=0.007, R=0.4 and p=0.002, R=0.5) in the AAIR mode. In conclusion in sick sinus syndrome with preserved LV function the DDDR mode does not compromise LV systolic function although it causes asynchrony. The NT-proBNP is lower when the right ventricle is paced, is inversely related to LV function and it is related to the degree of LV synchronization in the AAIR mode. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  1. Exenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium.

    Science.gov (United States)

    Wallner, Markus; Kolesnik, Ewald; Ablasser, Klemens; Khafaga, Mounir; Wakula, Paulina; Ljubojevic, Senka; Thon-Gutschi, Eva Maria; Sourij, Harald; Kapl, Martin; Edmunds, Nicholas J; Kuzmiski, J Brent; Griffith, David A; Knez, Igor; Pieske, Burkert; von Lewinski, Dirk

    2015-12-01

    Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart

  2. Echocardiography-based hemodynamic management of left ventricular diastolic dysfunction: a feasibility and safety study.

    Science.gov (United States)

    Shillcutt, Sasha K; Montzingo, Candice R; Agrawal, Ankit; Khaleel, Maseeha S; Therrien, Stacey L; Thomas, Walker R; Porter, Thomas R; Brakke, Tara R

    2014-11-01

    Patients with left ventricular diastolic dysfunction (LVDD) are at increased risk of postoperative adverse events. The primary aim of this study was to evaluate the safety and feasibility of using echocardiography-guided hemodynamic management (EGHEM) during surgery in subjects with LVDD compared to conventional management. The feasibility of using echocardiography to direct a treatment algorithm and clinical outcomes were compared for safety between groups. Subjects were screened for LVDD by preoperative transthoracic echocardiography (TTE) and randomized to the conventional or EGHEM group. Subjects in EGHEM received hemodynamic management based on left ventricular filling patterns on transesophageal echocardiography (TEE). Primary outcomes measured were the feasibility to obtain TEE images and follow a TEE-based treatment algorithm. Safety outcomes also compared the following clinical differences between groups: length of hospitalization, incidence of atrial fibrillation, congestive heart failure (CHF), myocardial infarction, cerebrovascular accident, transient ischemic attack and renal failure measured 30 days postoperatively. Population consisted of 28 surgical subjects (14 in conventional group and 14 in EGHEM group). Mean subject age was 73.4 ± 6.7 years (36% male) in conventional group and 65.9 ± 14.4 years (36% male) in EGHEM group. Procedures included orthopedic (conventional = 29%, EGHEM 36%), general (conventional = 50%, EGHEM = 36%), vascular (conventional = 7%, EGHEM = 21%), and thoracic (conventional = 14%, EGHEM = 7%). There was no statistically significant difference in adverse clinical events between the 2 groups. The EGHEM group had less CHF, atrial fibrillation, and shorter length of stay. Echocardiography-guided hemodynamic management of patients with LVDD during surgery is feasible and may be a safe alternative to conventional management. © 2014, Wiley Periodicals, Inc.

  3. Clinical Characteristics and Risk Factors of Left Ventricular Thrombus after Acute Myocardial Infarction: A Matched Case-control Study

    Directory of Open Access Journals (Sweden)

    Yue-Xin Jiang

    2015-01-01

    Conclusions: This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice.

  4. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study

    OpenAIRE

    Trupti Sarda; Surekha Rathod; Abhay Kolte; Girish Bodhare; Anil Modak

    2016-01-01

    Background: Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. Aim: This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM). Materials and Methods: ...

  5. Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Chen-Hui Ju

    2015-07-01

    Full Text Available Background/Aims: After myocardial infarction (MI, cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1 has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. Methods: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs stimulated by angiotensin II (Ang II was tested. Results: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. Conclusion: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.

  6. MRI diagnosis of right ventricular dysplasia; MRT-Diagnostik der rechtsventrikulaeren Dysplasie

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    Sommer, T.; Pauleit, D.; Hofer, U.; Schild, H. [Radiologische Universitaetsklinik Bonn (Germany); Lewalter, T.; Luederitz, B. [Medizinische Universitaetsklinik und Poliklinik Bonn (Germany); Bierhoff, E.; Pakos, E. [Bonn Univ. (Germany). Pathologisches Inst.; Smekal, A. v. [Universitaetsspital Zuerich (Switzerland). Inst. fuer Diagnostische Radiologie

    1998-12-01

    Purpose: Right ventricular dysplasia (RVD) represents an important cause of sudden death and ventricular arrhythmias in young patients. The aim of this study was to describe diagnostic criteria and the MR-tomographic aspects of the disease. Results: Right myocardial fatty infiltration was detected by MRI in 11 of 16 patients (69%) with RVD. Dilatation of the right ventricle was seen in 5 patients, dilatation of the right outflow tract in one patient, and localised right ventricular aneurysm in two patients with RVD. Conclusions: MRI is able to demonstrate fatty replacement of right ventricular myocardium in most cases and plays an important role in the diagnosis of RVD. (orig./AJ) [Deutsch] Ziel: Die rechtsventrikulaere Dysplasie (RVD) stellt eine in den letzten Jahren zunehmend beachtete Ursache ventrikulaerer Tachyarrhythmien und des ploetzlichen Herztodes bei juengeren Patienten dar. Ziel dieser Studie ist es, diagnostische Kriterien und MR-tomographische Aspekte der RVD darzustellen sowie die Wertigkeit der MRT im Nachweis der RVD-typischen lipomatoesen Degeneration des rechtsventrikulaeren Myokards zu evaluieren. Ergebnisse: Lipomatoeses rechtsventrikulaeres Ersatzgewebe konnte MR-tomographisch bei 11/16 Patienten (69%) mit RVD nachgewiesen werden. Des weiteren zeigte sich bei den Patienten mit gesicherter RVD eine RV-Dilatation in 5 Faellen, eine RVAT-Dilatation in einem Fall sowie aneurysmatische rechtsventrikulaere Wandaussackungen in zwei Faellen. Schlussfolgerungen: Die MRT kann das pathomorphologische Substrat der RVD, den fibro-lipomatoesen Ersatz des rechtsventrikulaeren Myokards, in einem Grossteil der Faelle darstellen und liefert damit einen entscheidenden Beitrag zur Diagnostik der RVD. (orig./AJ)

  7. ECMO Used in a Refractory Ventricular Tachycardia and Ventricular Fibrillation Patient: A National Case-Control Study.

    Science.gov (United States)

    Chen, Chih-Yu; Tsai, Ju; Hsu, Tai-Yi; Lai, Wan-Yu; Chen, Wei-Kung; Muo, Chih-Hsin; Kao, Chia-Hung

    2016-03-01

    Refractory cardiac arrhythmia, which has a poor response to defibrillation and antiarrhythmia medication, is a complicated problem for clinical physicians during resuscitation. Extracorporeal membrane oxygenation (ECMO) may be used to sustain life in this situation. ECMO is useful for cardiopulmonary resuscitation among patients suffering from cardiac arrest; the use of ECMO in this context is called E-cardiopulmonary resuscitation. However, a large-scale and nationwide survey of ECMO usage in cases involving refractory cardiac arrhythmia during resuscitation is lacking. We aimed to clarify the characteristics and efficacy of the application of ECMO in cases involving refractory cardiac arrhythmia during resuscitation by conducting a nationwide study. Using national insurance data from 1996 to 2011, 2702 patients who received defibrillation and amiodarone injections were selected. We excluded trauma patients (n = 316) and those aged1 day was higher risk of death (OR = 2.88, 95% CI = 1.27-6.53). In our retrospective case control study in refractory cardiac arrhythmia patients, ECMO supportive in high propensity score patients showed improving the overall survival rate but ECMO support for >1 day would be harmful. The evidence derived from this retrospective study using data from the national insurance system is generally of lower methodological evidence than that from randomized controlled trials because a retrospective study is subject to many biases due to lack of the necessary adjustments for possible confounding factors. Therefore, further investigation with a randomized clinical trial is needed to recommend ECMO as a routine in this specific population of patients experiencing cardiac arrest and refractory VT and VF.

  8. Hemodialysis-Induced Regional Left Ventricular Systolic Dysfunction and Inflammation : A Cross-sectional Study

    NARCIS (Netherlands)

    Assa, Solmaz; Hummel, Yoran M.; Voors, Adriaan A.; Kuipers, Johanna; Westerhuis, Ralf; Groen, Henk; Bakker, Stephan J. L.; Muller Kobold, Anneke C.; van Oeveren, Wim; Struck, Joachim; de Jong, Paul E.; Franssen, Casper F. M.

    Background: Hemodialysis may acutely induce regional left ventricular (LV) systolic dysfunction, which is associated with increased mortality and progressive heart failure. We tested the hypothesis that hemodialysis-induced regional LV systolic dysfunction is associated with inflammation and

  9. Myocardium wall thickness transducer and measuring method

    Science.gov (United States)

    Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

    1976-01-01

    A miniature transducer for measuring changes of thickness of the myocardium is described. The device is easily implantable without traumatizing the subject, without affecting the normal muscle behavior, and is removable and implantable at a different muscle location. Operating features of the device are described.

  10. Overexpression of M3 Muscarinic Receptor Suppressed Adverse Electrical Remodeling in Hypertrophic Myocardium Via Increasing Repolarizing K+ Currents

    Directory of Open Access Journals (Sweden)

    Xue Chen

    2017-09-01

    Full Text Available Background/Aims: Cardiac hypertrophy (CH is an adaptive response to diverse cardiovascular conditions, which is accompanied by adverse electrical remodeling manifested as abnormal K+ channel activities. M3 subtype of muscarinic acetylcholine receptor (M3-mAChR is a novel regulator of cardiac electrical activity. In this study we aim to explore if the overexpression of M3-mAChR could attenuate the adverse electrical remodeling in CH and then uncover its underlying electrophysiological mechanisms. Methods: Transgenic mice with M3-mAChR overexpression (M3-TG and wild type (WT mice were subjected to transverse aortic constriction (TAC to induce CH. Myocardial hypertrophy and cardiac function were quantified by the measurement of echocardiography, electrocardiogram, heart weight and tibia length. Whole-cell and signal-cell patch-clamp were employed to record electrophysiological properties by acute isolation of acutely isolated ventricular cardiomyocytes and Western blot was carried out to evaluate the Kir2.1and Kv4.2/4.3 protein levels in left ventricular tissue. Results: Compared with WT group, the elevation of cardiac index, including heart weight/body weight index and heart weight/tibia length index confirmed the myocardial hypertrophic growth induced by TAC. Echocardiography detection revealed that the TAC-treated mice showed an obvious increase in the thickness of left ventricular posterior wall (LVPW and ejection fraction (EF due to compensatory hypertrophy, which attenuated by the overexpression of M3-mAChR. Pressure overload induced a prolongation of QTc interval in WT mice, an effect blunted in M3-TG mice. Furthermore, compared with WT mice, M3-mAChR overexpression in hypertrophic myocardium accelerated cardiac repolarization and shortened action potential duration, and thus correcting the prolongation of QTc interval. Moreover, M3-TG mice have the greater current density of IK1 and Ito in ventricular myocytes after TAC compared with WT

  11. Noncoding RNA expression in myocardium from infants with tetralogy of Fallot.

    Science.gov (United States)

    O'Brien, James E; Kibiryeva, Nataliya; Zhou, Xin-Gang; Marshall, Jennifer A; Lofland, Gary K; Artman, Michael; Chen, Jie; Bittel, Douglas C

    2012-06-01

    The importance of noncoding RNAs (ncRNA), especially microRNAs (miRNAs), for maintaining stability in the developing vertebrate heart has recently become apparent; however, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of miRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, 3 fetal heart samples, and 8 normally developing infants. We found 61 miRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared with normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a surprising resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of miRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 miRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and 2 spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of genes that are critical for cardiac development. Taken together, these observations suggest a link between levels of snoRNA that target spliceosomal RNAs, spliceosomal function, and heart development. This is the first report characterizing ncRNA expression in a congenital heart defect. The striking shift in expression of nc

  12. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study.

    Science.gov (United States)

    Penicka, Martin; Gregor, Pavel; Kerekes, Roman; Marek, Dan; Curila, Karol; Krupicka, Jiri

    2009-01-01

    Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.

  13. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction

    Science.gov (United States)

    Zhang, Dongze; Tu, Huiyin; Wang, Chaojun; Cao, Liang; Muelleman, Robert L.; Wadman, Michael C.; Li, Yu-Long

    2017-01-01

    Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats. Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF. Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF. PMID:28533740

  14. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Dongze Zhang

    2017-05-01

    Full Text Available Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF. Our recent study demonstrates that N-type Ca2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats.Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP and the maximum rate of left ventricular pressure rise (LV dP/dtmax in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF.Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

  15. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction.

    Science.gov (United States)

    Zhang, Dongze; Tu, Huiyin; Wang, Chaojun; Cao, Liang; Muelleman, Robert L; Wadman, Michael C; Li, Yu-Long

    2017-01-01

    Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca(2+) currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats. Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca(2+) currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca(2+) currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca(2+) currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF. Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

  16. Quantification of myocardium at risk in myocardial perfusion SPECT by co-registration and fusion with delayed contrast-enhanced magnetic resonance imaging--an experimental ex vivo study.

    Science.gov (United States)

    Ugander, Martin; Soneson, Helen; Engblom, Henrik; van der Pals, Jesper; Erlinge, David; Heiberg, Einar; Arheden, Håkan

    2012-01-01

    Myocardial perfusion single-photon emission computed tomography (MPS) can be used to assess myocardium at risk in occlusive coronary ischaemia. The aim was to develop a method to quantify myocardium at risk as perfusion defect size on ex vivo MPS using co-registration and fusion with ex vivo magnetic resonance imaging (MRI). Pigs (n = 19) were injected 99mTc-tetrofosmin prior to concluding 40 min of coronary artery occlusion, followed by reperfusion and MRI contrast injection. The excised heart was imaged with T1-weighted MRI and MPS, and images were co-registered using freely available software (Segment v1.8, http://segment.heiberg.se). The left ventricle was semi-automatically delineated in MRI and copied to MPS. The threshold for a MPS perfusion defect was defined as the mean counts in the MPS image at the MRI-determined border between remote myocardium and air. The threshold was measured using count maxima set to the 100th-95th percentile of counts within the myocardium. The count maximum that gave the lowest threshold variability (SD) was considered the most robust. A count maximum using the 100th percentile yielded a threshold of (mean ± SD) 55 ± 6·2%. This method showed the lowest SD compared to 99th-95th percentile count maxima (6·6-7·2%). We describe a method for objective quantification of myocardium at risk as perfusion defect size on MPS using knowledge of the anatomy of the myocardium from co-registered MRI. This enables simultaneous quantification of myocardium at risk by MPS and infarct size by MRI for the evaluation of treatments for myocardial infarction. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  17. Extracorporeal life support with left ventricular decompression—improved survival in severe cardiogenic shock: results from a retrospective study

    Directory of Open Access Journals (Sweden)

    Bastian Schmack

    2017-09-01

    Full Text Available Objective Extracorporeal life support (ECLS is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression. Methods Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years, who received either central ECLS with (n = 20, 41.7% or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS integrated left ventricular vent in our retrospective single centre trial. Results Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14, bridge to transplant in 10.4% (n = 5 and bridge to recovery in 8.3% (n = 4. Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034. Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent. Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival. Conclusion ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.

  18. Post-repolarization refractoriness increases vulnerability to block and initiation of reentrant impulses in heterogeneous infarcted myocardium.

    Science.gov (United States)

    Cabo, Candido

    2015-10-01

    Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct. (1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts

  19. Transmural heterogeneity of myofilament function and sarcomeric protein phosphorylation in remodelled myocardium of pigs with a recent myocardial infarction

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    Jolanda evan der Velden

    2011-11-01

    Full Text Available Transmural differences in sarcomeric protein composition and function across the left ventricular (LV wall have been reported. We studied sarcomeric function and protein phosphorylation in subepicardial (EPI and subendocardial (ENDO layers of remote LV pig myocardium after infarction (MI, induced by left circumflex coronary artery ligation. EPI and ENDO samples were taken 3 weeks after sham surgery (n=12 or induction of MI (n=12 at baseline and after β-adrenergic receptor (βAR stimulation with dobutamine. Isometric force was measured in single cardiomyocytes at various [Ca2+] and 2.2 μm sarcomere length. In sham hearts, no significant transmural differences were observed in myofilament function or protein phosphorylation. Myofilament Ca2+-sensitivity was significantly higher in both EPI and ENDO of MI compared to sham hearts. Maximal force was significantly reduced in MI compared to sham, but solely in ENDO cells. A higher passive force was observed in MI hearts, but only in EPI cells. The proportion of stiff N2B isoform was higher in EPI than in ENDO in both sham and MI hearts, and a trend towards increased N2B-proportion appeared in MI EPI, but not MI Endo. Analysis of myofilament protein phosphorylation did not reveal significant transmural differences in phosphorylation of myosin binding protein C, desmin, troponin T, troponin I (cTnI and myosin light chain 2 (MLC-2 both at baseline and after βAR stimulation with dobutamine infusion. A significant increase in MLC-2 phosphorylation was observed during dobutamine only in sham. In addition, the increase in cTnI phosphorylation upon dobutamine was 2-fold lower in MI than in sham.Myofilament dysfunction is present in both EPI and ENDO in post-MI remodelled myocardium, but shows a high degree of qualitative heterogeneity across the LV wall. These heterogeneous transmural changes in sarcomeric properties likely contribute differently to systolic versus diastolic global LV dysfunction after MI.

  20. [Impact of chronic Chlamydia pneumoniae infection on left ventricular remodeling after myocardial infarction].

    Science.gov (United States)

    Marcinkowski, Marcin; Czarnecka, Danuta; Jastrzebski, Marek; Fedak, Danuta; Kawecka-Jaszcz, Kalina

    2006-01-01

    Postmyocardial infarction left ventricular remodeling is modified by inflammatory processes and structural changes in the myocardium. Chlamydia pneumoniae (Chp) causes chronic myocyte infection, affects apoptosis and TNF-alpha production, and may induce cross reactivity with alpha myosin. This is the way in which this intracellular pathogen may modulate remodeling on the cellular and organ level. The study was conducted in 101 patients with a first myocardial infarction in whom we evaluated the serological features of Chp infection using the ELISA method and echocardiographic left ventricular volume at 10 days and 10 weeks after the infarction. Patients with chronic Chp infection had a tendency toward higher end-diastolic volume at 10 weeks after the infarction (123 +/- 32.9 ml vs. 134 +/- 34.7 ml, p = 0.09). In order to better define this relationship we used ROC analysis and measured levels of antibodies: IgG = 117 EIU and IgA = 15.6 EIU by which we divided the patients into two subgroups. Those with IgG > or = 117 EIU and IgA > or = 15.6 EIU belong to the subgroup with chronic and active Chp infection. These patients had larger left ventricular end-diastolic volumes (155.8 vs. 123.1 ml, p = 0.0005) and end-systolic volumes (77.4 vs. 59.5 ml, p = 0.006) at 10 weeks after the infarction. Both subgroups were similar with respect to age, gender, history of arterial hypertension, systolic and diastolic blood pressure values, infarct site, reperfusion, infarct size, left ventricular ejection fraction and left ventricular contractility index. Type of reperfusion therapy and pharmacological treatment at 10 days and at 10 weeks did not differ, either. Chronic Chlamydia pneumonie infection modifies the course of left ventricular remodeling.

  1. The overloaded right heart and ventricular interdependence.

    Science.gov (United States)

    Naeije, Robert; Badagliacca, Roberto

    2017-10-01

    The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights

  2. Revascularization among patients with severe left ventricular dysfunction: a meta-analysis of observational studies.

    Science.gov (United States)

    Kunadian, Vijayalakshmi; Zaman, Azfar; Qiu, Weiliang

    2011-07-01

    Coronary artery bypass graft (CABG) surgery is the standard of care for the management of patients with severe three-vessel and left main coronary artery disease (CAD). However, the optimal strategy for management of patients with CAD and severe left ventricular (LV) dysfunction [ejection fraction (EF) ≤35%] is not clear. A meta-analysis of observational studies was performed to determine the operative mortality and long-term (5-year actuarial survival) outcomes among patients with severe LV dysfunction undergoing CABG. A systematic computerized literature search was performed and observational studies consisting of patients undergoing isolated CABG for CAD and severe LV dysfunction were included. Studies that did not report operative mortality, long-term (≥1 year) survival data, or pre-operative EF and multiple studies from the same group were excluded. In total, 4119 patients from 26 observational clinical studies were included. The estimated mean age was 63.9 years and 82.4% of patients were men. The mean (estimate) pre-operative EF was 24.7% (95% CI 22.5-27.0%). The operative mortality among patients (26 studies, n= 3621) who underwent on-pump CABG was 5.4%, n= 189 (95% CI 4.5-6.4%). The 5-year actuarial survival among patients (13 studies, n= 1980) who underwent on-pump CABG was 73.4%, n= 1483 (95% CI 68.7-77.7%). Patients who underwent off-pump CABG (7 studies, n= 498) tended to have reduced operative mortality of 4.4%, n= 20 (95% CI 2.8-6.4%). The mean (estimate) post-operative EF was 35.19% (95% CI 31.95-38.43%). The present meta-analysis demonstrates that based on data from available observational clinical studies, CABG can be performed with acceptable operative mortality and 5-year actuarial survival in patients with severe LV dysfunction.

  3. Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

    Science.gov (United States)

    Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

    2016-04-15

    It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Association between alcohol consumption and systolic ventricular function: a population-based study.

    Science.gov (United States)

    Yousaf, Haroon; Rodeheffer, Richard J; Paterick, Timothy E; Ashary, Zain; Ahmad, Mirza Nubair; Ammar, Khawaja Afzal

    2014-06-01

    Although moderate alcohol consumption is associated with decreased clinical heart failure, there are no population-based studies evaluating the relationship between alcohol consumption and left ventricular (LV) systolic function. We sought to evaluate the relationship between alcohol consumption and LV systolic function in the community. In a population-based random sample of 2,042 adults, age ≥45 years, we assessed alcohol consumption by a self-administered questionnaire. Responders were categorized by alcohol consumption level: abstainer, former drinker, light drinker (2 drinks a day). Systolic function was assessed by echocardiography. We identified 38 cases of systolic dysfunction in 182 abstainers, 309 former drinkers, 1,028 light drinkers, 251 moderate drinkers, and 146 heavy drinkers. A U-shaped relationship was observed between alcohol consumption and moderate systolic dysfunction (LV ejection fraction [LVEF] ≤40%), with the lowest prevalence in light drinkers (0.9%) compared to the highest prevalence in heavy drinkers (5.5%) (odds ratio 0.14, 95% CI 0.04-0.43). This association persisted across different strata of risk factors of systolic dysfunction as well as in multivariate analysis. No significant association between alcohol consumption and systolic function was seen in subjects with LVEF >50% or ≤50%. There is a U-shaped relationship between alcohol consumption volume and LVEF, with the lowest risk of moderate LV dysfunction (LVEF ≤40%) observed in light drinkers (consumption and cardiovascular disease prevalence. Copyright © 2014 Mosby, Inc. All rights reserved.

  5. T1 mapping for detection of left ventricular myocardial fibrosis in hypertrophic cardiomyopathy: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Minjie [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhao, Shihua, E-mail: coolkan@163.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yin, Gang; Jiang, Shiliang; Zhao, Tao; Chen, Xiuyu [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tian, Liangxin [Department of Cardiac Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Yan; Wei, Yunqing; Liu, Qiong [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); He, Zuoxiang [Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xue, Hui [Siemens Healthcare, 737 N. Michigan Avenue, Suite 1600 Chicago, IL 60611 (United States); An, Jing [Siemens Shenzhen Magnetic Resonance Ltd. Application Dept. Siemens MRI center, Gaoxin C. Ave.,2nd, Hi-Tech Industrial Park, Shenzhen (China); Shah, Saurabh [Siemens Healthcare, 737 N. Michigan Avenue, Suite 1600 Chicago, IL 60611 (United States)

    2013-05-15

    Purpose: To investigate the diagnostic value of T1 mapping imaging of evaluating fibrosis in patients with hypertrophic cardiomyopathy (HCM). Materials and methods: 21 subjects with HCM and 18 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 mapping imaging. The region of myocardium in HCM is divided into remote area of LGE, peri-LGE, LGE (halo-like LGE and typical patchy LGE). These regions combined with normal volunteers’ myocardium were calculated by the reduced percent of T1 value (RPTV). Results: The RPTV in healthy volunteers was no significant comparing with that in the remote area of LGE in HCM subjects (3.98 ± 3.19 vs. 3.34 ± 2.75, P > 0.05). There were significant statistical differences in pairwise among the remote area of LGE, peri-LGE, halo-like LGE and typical patchy LGE in the RPTV (P < 0.0001). ROC curves indicated that the T1 mapping imaging has a greater area under the curve comparing with that of traditional LGE imaging (0.975 ± 0.07 vs. 0.753 ± 0.26, P < 0.0001). Conclusions: HCM has a high prevalence of fibrosis and with varying severity. T1 mapping imaging can be a useful method to evaluate the severity of the fibrosis in HCM.

  6. Increased expression of Dock180 protein in the noninfarcted myocardium in rats.

    Science.gov (United States)

    Liu, Xiao-Lan; Li, Gang; Wang, Zhi-Hua; Zhao, Wen-Ju; Wang, Li-Ping

    2013-03-01

    The integrin β1 subunit and its downstream molecule focal adhesion kinase have been identified as critical molecules for the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. However, as a component of the integrin pathway, it is still unclear whether Dock180 (dedicator of cytokinesis 1) protein is expressed in the noninfarcted myocardium of the peri-infarct zones. In this study, experimental myocardial infarction (MI) and sham-operation (sham) models were established in Sprague Dawley rats and the expression of Dock180 protein in the myocardium of the sham group and in the noninfarcted myocardium of the peri-infarct zones of the MI group was detected by Western blot technique. The Dock180 protein expression in the myocardium was as follows: postsham 24-hour group, 0.10 ± 0.04 (n = 8); post-MI 24-hour group, 0.13 ± 0.03 (n = 8); postsham 12-week group, 0.11 ± 0.05 (n = 8); and post-MI 12-week group 0.17 ± 0.04 (n = 8). The Dock180 protein expression in the myocardium in the post-MI 12-week group was significantly higher than that in the postsham 12-week group (p = 0.019), in the postsham 24-hour group (p = 0.004), and in the post-MI 24-hour group (p = 0.040). We conclude that Dock180 protein is expressed in the myocardium in rats. Furthermore, its expression is significantly increased in the noninfarcted myocardium of the peri-infarct zones. Copyright © 2012. Published by Elsevier B.V.

  7. A prospective study found impaired left ventricular function predicted job retirement after acute myocardial infarction

    DEFF Research Database (Denmark)

    Nielsen, Finn E; Sørensen, Henrik T; Skagen, Knud

    2004-01-01

    adjusting for confounding factors, reduced LVEF was an independent predictor of retirement. Based on a stratified analysis, being female (RR=3.90, 95% CI=1.18-12.62) or having heavy physical job demands (RR=3.83, 95% CI=1.02-14.30) had a more pronounced impact on retirement for patients with LVEF 35......%, compared with patients with better left ventricular function. CONCLUSION: We conclude that impaired left ventricular systolic function is a prognostic determinant of retirement from the job market after acute MI....

  8. Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study.

    Science.gov (United States)

    Verdecchia, P; Carini, G; Circo, A; Dovellini, E; Giovannini, E; Lombardo, M; Solinas, P; Gorini, M; Maggioni, A P

    2001-12-01

    This study investigated the prognostic value of left ventricular (LV) mass at echocardiography in uncomplicated subjects with essential hypertension. Only a few single-center studies support the prognostic value of LV mass in uncomplicated hypertension. The MAssa Ventricolare sinistra nell'Ipertensione study was a multicenter (45 centers) prospective study. The prespecified aim was to explore the prognostic value of LV mass in hypertension. Admission criteria included essential hypertension, no previous cardiovascular events, and age > or =50. There was central reading of echocardiographic tracings. Treatment was tailored to the single subject. Overall, 1,033 subjects (396 men) were followed for 0 to 4 years (median, 3 years). Mean age at entry was 60 years, and systolic/diastolic blood pressure was 154/92 mm Hg. The rate of cardiovascular events (x100 patient-years) was 1.3 in the group with normal LV mass and 3.2 in the group (28.5% of total sample) with LV mass > or =125 g/body surface area (p = 0.005). After adjustment for age (p < 0.01), diabetes (p < 0.01), cigarette smoking (p < 0.01) and serum creatinine (p = 0.03), LV hypertrophy was associated with an increased risk of events (RR [relative risk] 2.08; 95% CI [confidence interval]: 1.22 to 3.57). For each 39 g/m(2) (1 SD) increase in LV mass there was an independent 40% rise in the risk of major cardiovascular events (95% CI: 14 to 72; p = 0.0013). Our findings show a strong, continuous and independent relationship of LV mass to subsequent cardiovascular morbidity. This is the first study to extend such demonstration to a large nationwide multicenter sample of uncomplicated subjects with essential hypertension.

  9. Impact of the permanent ventricular pacing site on left ventricular function in children: A retrospective multicentre survey

    NARCIS (Netherlands)

    I.E. van Geldorp (Irene); T. Delhaas (Tammo); R.A. Gebauer (Roman); P. Frias (Patrick); M. Tomaske (Maren); M.K. Friedberg (Mark); S. Tisma-Dupanovic (Svjetlana); J. Elders (Jan); A. Früh (Andreas); F. Gabbarini (Fulvio); P. Kubuš (Petr); V. Illikova (Viera); E.C. Tsao (Elisa); A.C. Blank (Andreas Christian); A. Hiippala (Anita); T. Sluysmans (Thierry); P. Karpawich (Peter); S.A. Clur (Sally-Ann); X. Ganame (Xavier); K.K. Collins (Kathryn); G.C. Dann (Greg); J.-B. Thambo (Jean-Benoît); C. Trigo (Conceição); B. Nagel (Bert); J. Papagiannis (John); A. Rackowitz (Annette); J. Marek (Josef); J.-H. Nürnberg (Jan-Hendrik); W.Y. Vanagt (Ward); F.W. Prinzen (Frits); J. Janousek (Jan)

    2011-01-01

    textabstractBackground: Chronic right ventricular (RV) pacing is associated with deleterious effects on cardiac function. Objective In an observational multicentre study in children with isolated atrioventricular (AV) block receiving chronic ventricular pacing, the importance of the ventricular

  10. Clinical Profile and Prognosis of Patients with Right Ventricular Dilated Cardiomyopathy: Results of a Prospective Study

    Directory of Open Access Journals (Sweden)

    Ya.R. Akhmatov

    2015-12-01

    Full Text Available The aim of our study was to investigate the clinical prevalence of dilated cardiomyopathy (DCM with predominantly failure of the right-side heart (right ventricular DCM, RV-DCM, and features of the clinical course and prognosis of the disease compared to DCM with biventricular heart failure (BV-HF. The study design suggests a prospective observation of 300 patients with idiopathic DCM between 2000 and 2012. Herewith, we followed the criteria of the WHO/ISFC Task Force (1995 on the Definationa and Classification of Cardiomyopathies. All patients underwent a comprehensive examination. Two groups were formed for further comparative analysis. Group 1 included 22 patients (mean age 42.9±14.3 years, male/female 5/17 with RV-DCM. Group 2 included 38 patients (mean age 43.6±13.8, male/female 29/9 with DCM and BV-HF. The groups were matched for age, sex, NYHA class II-III, and disease duration. According to our aim, we studied 5-year survival prognosis and analyzed the incidence and causes of deaths, as well as the occurrence of nonfatal complications of the disease. Medical therapy for DCM patients was performed according to the CHF therapy guidelines (ACC/AHA 2001, 2005. The results of our investigations during many years of research have shown that the clinical incidence of RV-DCM was 7.3% among all forms of DCM. The study of life prognosis in patients with 2 forms of DCM showed that 5-year mortality of patients was about 50%. Herewith, we detected the differences in causes of death depending on the type of heart damage, primarily development of fatal pulmonary embolism.

  11. Theoretical Model of Coronary Blood Flow Regulation: Role of Myocardium Compressive Forces.

    Science.gov (United States)

    Xie, Xinzhou; Wang, Yuanyuan

    2015-11-01

    Auto-regulatory reserve of coronary blood flow is nonuniformly distributed across the ventricular wall. MCF are thought to play an important role in determining the transmural distribution of myocardium blood flow. Here, impacts of MCF on coronary flow regulation are analyzed using a theoretical model. Coronary microvessels at various depths in the ventricular wall are represented by parallel segments. Nine vessel regions are connected in series to represent one parallel segment, which includes four vasoactive regions regulated by the wall tension, the shear stress and the metabolic demand. The nonuniform distribution of MCF is modeled and its effects on coronary flow regulation are taken into consideration by using a modified tension model and a vessel collapse model. Flow regulation behaviors in both normal and obstructed coronary circulation are simulated. Model-predicted auto-regulatory curve is shifted to the high pressure region by including the effect of MCF. Model-predicted flow distributions in obstructed coronary circulation show that severe stenosis in coronary artery would first impede myocardial blood flow in subendocardial layer. The model results indicate that MCF plays an important role in coronary flow regulation and also in determining the transmural distribution of myocardium blood flow. © 2015 John Wiley & Sons Ltd.

  12. Reduced expression of CRHR2 and Sp-1 in myocardium of ovariectomized rats is improved by exercise training.

    Science.gov (United States)

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Cong, Binhai; Lu, Jianqiang

    2015-01-01

    Exercise training has been looked on as a non-pharmacologic approach to treating ovariectomy (OVX)-induced dysfunctions. In this study, we investigated whether chronic exercise impacts on expression of urocortins (UCNs) and corticotropin-releasing hormone receptor type 2 (CRHR2) in myocardium of OVX rats. Bilateral OVX or sham-operation was performed under anesthesia. Both groups were then divided into two subgroups, with or without treadmill training for 8 weeks. It was found that OVX as well as exercise did not affect the mRNA levels of UCN, UCN2 and UCN3 in myocardium. OVX caused down-regulation of CRHR2 in myocardium. Exercise training reversed the OVX-induced reduction of CRHR2, but had no influence on CRHR2 level in sham rats. OVX resulted in a decrease in estrogen receptor α (ERα) expression in myocardium, which was restored by exercise. Moreover, exercise training also reversed OVX-induced down-regulation of specific protein-1 (Sp-1) expression in myocardium. CRHR2 expression level correlated with Sp-1 and ERα level in myocardium. These results indicate that exercise training can restore the CRHR2 level in myocardium of OVX rats, which is associated with ERα and Sp-1 expression.

  13. [Arrhythomgenic right ventricular dysplasia and sudden death: An autopsy and histological study].

    Science.gov (United States)

    Haj Salem, N; Mesrati, M A; Hadhri, R; Besbes, S; Belhadj, M; Aissaoui, A; Zakhama, A; Chadly, A

    2015-09-01

    Arrhythmogenic right ventricular dysplasia (ARVD) is cardiomyopathy where normal myocardial tissue is replaced with fibrofatty tissue. Histological examination performed on myocardial biopsy or on autopsy samples are used to confirm the diagnosis. However, in many cases, the diagnosis cannot be made on a simple macroscopic and histological study and requires genetic analysis and molecular biology. In this work, we propose to describe the main macroscopic and histological findings of ARVD through the study of an autopsy series. We report 12 autopsy cases of sudden death in ARVD collected in the Department of Forensic Medicine of the University Hospital Fattouma Bourguiba Monastir (Tunisia) during a period of 20years. Microscopic examination was performed on 5microns thick histological sections. All slides were reviewed by two operators in a double blind (physician pathologist, pathologist) and in each, the percentage of adipose tissue, fibrosis and infarction in the right ventricle, left ventricle and interventricular septum, the presence or absence of inflammatory infiltrate, the presence or absence of signs of degeneration of myocytes were noticed. ARVD was found in 12 cases (1.8% of sudden cardiac death). The age ranged between 13 and 67years (mean age: 45.3years). The death occurred in half of the cases during exercise. Macroscopic examination of the RV showed the presence of a wall thinning (thickness<3mm) in 9 cases. Histological study highlight RV adipose infiltration in all cases with a percentage between 15% and 60%, fibrotic lesions were observed in only 9 cases with an average percentage of 10.25% and signs of degeneration of myocytes were noted in 10 cases. In concordance with what has been reported in the literature, there is still no consensus regarding the criteria to be adopted to pose with certainty the diagnosis of ARVD and the presence of adipose tissue remains the criterion more suggestive. Copyright © 2015. Published by Elsevier SAS.

  14. Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study.

    Science.gov (United States)

    Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

    2015-11-01

    Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

  15. Effects of acute and chronic uremia on active cation transport in rat myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  16. HISTOLOGICAL AND HISTOCHEMICAL CHARACTERISTICS OF RAT MYOCARDIUM IN CADMIUM TOXICOSIS

    Directory of Open Access Journals (Sweden)

    Novica Bojanić

    2013-01-01

    Full Text Available Carcinogenic effects of cadmium on lungs, testicles and prostate are well known, so as cumulative and toxic effects on kidney, liver and bones; however, there have not been many published articles about the effects of cadmium on myocardium. The aim of this study was to estimate the morphological changes in rat myocardium chronically treated by cadmium. The study was carried out on male albino Wistar rats (n=30, age=35-37 days, body mass 120g +/- 10g. The animals were raised in controlled laboratory conditions and provided with standard laboratory rat food and tap water ad libitum. The rats were divided into two groups: ten animals composed the control group and did not undergo any treatment. The 20 experimental rats were exposed to 10mg of CdCl2 /L drinking water for 90 days. After 90 days, all animals were victimized and after the macroscopic inspection of the heart, myocardial tissue was routinely processed and embedded in paraffin. Sections 5 micrometers thick were stained by HE method and histochemical PAS-AB (pH 2, 5, Masson trichrome method for demonstrating collagen fibers and Toluidine blue for mast cells identification. Cross-striated banding pattern of cardiac cells was ruined. Noticeable atrophy and hydropic degeneration of subendocardial localized cardiac cells were found, with the focal presence of myocytolysis. Endothelial cell hyperplasia and edema of the intima were present on arteriolar type blood vessels causing the focal subocclusion. Fibrocytes, histiocytes and mast cells were numerous, perivascularly localized. Mast cells were polymorphic, larger than normal, oval and mostly degranulated. Instead of scanty endomysium, there is a noticeable interstitial fibrillar fibrosis with few fields of collagen in all myocardium layers between cardiac cells, which is particularly prominent around the larger blood vessels. Cadmium has pronounced vasculotropic properties causing morphological changes of cardiomyocytes, myocardial

  17. Preservation of CGRP in myocardium attenuates development of cardiac dysfunction in diabetic rats.

    Science.gov (United States)

    Sun, Tao; Guo, Zheng; Liu, Chao-Jie; Li, Mu-Rong; Li, Tu-Ping; Wang, Xin; Yuan, Da-Jiang

    2016-10-01

    Calcitonin gene-related peptide (CGRP) plays an important role in cardiovascular regulation, which was found reduced in serum of diabetic patients. To test the hypothesis that lack of CGRP in myocardium is associated with diabetic cardiac dysfunction, which may be improved by preservation of CGRP in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by streptozotocin (50mg/kg). Two groups of the diabetic rats, one fed with standard laboratory chew and another with the laboratory food plus hot pepper (containing 0.0174% of capsaicin), to stimulate production and release of CGRP. Cardiac functions were evaluated by measurements of intraventricular pressures after 8weeks of development of diabetes. Transient receptor potential vanilloid type 1 (TRPV1), CGRP, β1-adreneregic receptor and norepinephrine were analyzed. Significantly lower levels of TRPV1 and CGRP were detected in the thoracic dorsal root ganglia (DRG) and myocardium of the diabetic animals, along with significant decline in left ventricular systolic pressure (by 24%) and heart rate (by 25%) and increase of the end-diastolic pressure (by 83%) with obvious reduction of CGRP in the DRG, by 41%, the myocardium (by 30%) and the serum (by 20%). The cardiac performance, the TRPV1 and the CGRP in the diabetic animals fed with hot pepper were well preserved. No any significant change in β1-adreneregic receptor and norepinephrine was detected. The findings may suggest a novel mechanism underlying diabetic cardiac dysfunctions via impairing TRPV1-CGRP pathway in myocardium. Preservation of the TRPV1-CGRP mechanism may prevent the development of cardiac dysfunction in diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    Energy Technology Data Exchange (ETDEWEB)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Mongillo, Marco; Khan, Muhammad T. [Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); Depre, Christophe [University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, New Jersey, NJ (United States); University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Medicine, New Jersey, NJ (United States); Rimoldi, Ornella E. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); New York Medical College, Cardiovascular Research Institute, Department of Medicine, Valhalla, NY (United States); Camici, Paolo G. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom)

    2007-12-15

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([{sup 11}C]meta-hydroxy-ephedrine; HED) and {beta}-adrenoceptor ({beta}-AR) density ([{sup 11}C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V{sub d}) of HED in HM (47.95{+-}28.05 ml/g) and infarcted myocardium (42.69{+-}25.76 ml/g) was significantly reduced compared with controls (66.09{+-}14.48 ml/g). The V{sub d} of HED in normal myocardium (49.93{+-}20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial {beta}-AR density was significantly lower in HM (5.49{+-}2.35 pmol/g), infarcted (4.82{+-}2.61 pmol/g) and normal (5.86{+-}1.81 pmol/g) segments of patients compared with healthy controls (8.61{+-}1.32 pmol/g). Noradrenaline uptake-1 mechanism and {beta}-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  19. Partition coefficients for gadolinium chelates in the normal myocardium: comparison of gadopentetate dimeglumine and gadobenate dimeglumine.

    Science.gov (United States)

    Kawel, Nadine; Nacif, Marcelo; Santini, Francesco; Liu, Songtao; Bremerich, Jens; Arai, Andrew E; Bluemke, David A

    2012-09-01

    To evaluate the influence of contrast agents with different relaxivity on the partition coefficient (λ) and timing of equilibration using a modified Look-Locker inversion recovery (MOLLI) sequence in cardiac magnetic resonance imaging (MRI). MOLLI was acquired in 20 healthy subjects (1.5T) at the mid-ventricular short axis precontrast and 5, 10, 20, 25, and 30 minutes after administration of a bolus of 0.15 mmol/kg gadobenate dimeglumine (Gd-BOPTA) (n = 10) or gadopentetate dimeglumine (Gd-DTPA) (n = 10). T1 times were measured in myocardium and blood pool. λ was approximated by ΔR1(myocardium) /ΔR1(blood) . Values for Gd-BOPTA and Gd-DTPA were compared. Interobserver agreement was evaluated (intraclass correlation coefficient [ICC]). T1 times of myocardium and blood pool (P < 0.001) and λ (0.42 ± 0.03 and 0.47 ± 0.04, respectively, P < 0.001; excluding 5 minutes for Gd-BOPTA) were significantly lower for Gd-BOPTA than Gd-DTPA. The λ((Gd-DTPA)) showed no significant variation between 5 and 30 minutes. The λ((Gd-BOPTA)) values were significantly lower at 5 minutes compared to other times (0.38 vs. 0.42; P < 0.05). Interobserver agreement for λ values was excellent with Gd-BOPTA (ICC = 0.818) and good for Gd-DTPA (ICC = 0.631). The λ((Gd-BOPTA)) values were significantly lower compared to λ((Gd-DTPA)) at the same administered dose. Using Gd-BOPTA, the equilibrium between myocardium and blood pool was not achieved at 5 minutes postcontrast. Copyright © 2012 Wiley Periodicals, Inc.

  20. Experimental study on the effect of an artificial cardiac valve on the left ventricular flow

    Science.gov (United States)

    Wang, JiangSheng; Gao, Qi; Wei, RunJie; Wang, JinJun

    2017-09-01

    The use of artificial valves to replace diseased human heart valves is currently the main solution to address the malfunctioning of these valves. However, the effect of artificial valves on the ventricular flow still needs to be understood in flow physics. The left ventricular flow downstream of a St. Jude Medical (SJM) bileaflet mechanical heart valve (BMHV), which is a widely implanted mechanical bileaflet valve, is investigated with time-resolved particle image velocimetry in the current work. A tilting-disk valve is installed on the aortic orifice to guarantee unidirectional flow. Several post-processing tools are applied to provide combined analyses of the physics involved in the ventricular flow. The triple jet pattern that is closely related to the characteristics of the bileaflet valve is discussed in detail from both Eulerian and Lagrangian views. The effects of large-scale vortices on the transportation of blood are revealed by the combined analysis of the tracking of Lagrangian coherent structures, the Eulerian monitoring of the shear stresses, and virtual dye visualization. It is found that the utilization of the SJM BMHV complicates the ventricular flow and could reduce the efficiency of blood transportation. In addition, the kinematics of the bileaflets is presented to explore the effects of flow structures on their motion. These combined analyses could elucidate the properties of SJM BMHV. Furthermore, they could provide new insights into the understanding of other complex blood flows.

  1. Procollagen type III amino terminal peptide and myocardial fibrosis: A study in hypertensive patients with and without left ventricular hypertrophy.

    Science.gov (United States)

    dos Santos Moreira, Carlos; Serejo, Fátima; Alcântara, Paula; Ramalhinho, Vítor; Braz Nogueira, J

    2015-05-01

    An exaggerated accumulation of type I and type III fibrillar collagens occurs throughout the free wall and interventricular septum of patients with primary hypertension and left ventricular hypertrophy (LVH). In the present study the serum concentration of procollagen type III amino terminal peptide (PIIIP) was measured to determine the value of this peptide as a potential marker of ventricular fibrosis in hypertensive patients, particularly those with LVH. The study population consisted of patients with never-treated mild to moderate essential hypertension and 30 normotensive control subjects. Clinical, echocardiographic, electrocardiographic and biochemical parameters were assessed in all patients. Heart rate, body mass index and levels of blood pressure were increased in hypertensives, particularly those with LVH, compared to normotensive controls. Posterior wall thickness, left ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also increased in hypertensives, with significant differences between the two hypertensive groups. The ratio between maximal early and late transmitral flow velocity measured during diastole was lower in hypertensives, particularly those with LVH, than in normotensive controls. The increase in PIIIP indicates that type III collagen synthesis increases in hypertensives, particularly those with LVH, implying that alterations in the heart in hypertension are the result not solely of hypertrophied LV muscle, but also of increased collagen deposition within the ventricular wall and around the coronary vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in the non-invasive assessment of myocardial remodeling in hypertension. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  2. Variability and reproducibility of rubidium-82 kinetic parameters in the myocardium of the anesthetized canine.

    Science.gov (United States)

    Coxson, P G; Brennan, K M; Huesman, R H; Lim, S; Budinger, T F

    1995-02-01

    Kinetic analysis of 82Rb dynamic PET data produces quantitative measures which could be used to evaluate ischemic heart disease. These measures have the potential to generate objective comparisons of different patients or the same patient at different times. To achieve this potential, it is essential to determine the variability and reproducibility of the kinetic parameters. A total of 48 82Rb dynamic PET datasets were acquired from two pure bred beagles. Each animal underwent eight 82Rb PET studies with essentially the same protocol for three successive weeks. Data were acquired with the Donner 600-Crystal Positron Tomograph (PET600). In each week, single-slice dynamic 82Rb PET datasets were collected with the animal at rest at three different gantry positions separated by 5 mm. Additional dataset were collected after dipyridamole infusion and after administration of aminophylline to induce a return to rest. A two-compartment kinetic model with correction for myocardial vasculature and spillover from the left ventricular blood pool was used to analyze the dynamic datasets. Model parameters for uptake (k1), washout (k2) and vascular fraction (fv) were estimated in 11-14 myocardial regions of interest (ROIs) using a weighted least-squares criterion. Statistical fluctuation due to the PET acquisition process was minimized by using a relatively high 82Rb dose (about 30 mCi) to take advantage of the high count rate capacity of the PET600. The variation in mean k1, where the mean is taken over the myocardial ROIs was 10%-20% (Dog 1) and 15%-50% (Dog 2) among the rest studies conducted on the same date. Similar variation was evident in comparing studies in the same animal for different weeks. Spatial and temporal variation in estimates of the uptake rate (k1) of 82Rb in the resting myocardium of the anesthetized canine are small in relation to the functional increase in k1 following dipyridamole infusion.

  3. Improved Left Ventricular Diastolic Function with Exercise Training in Hypertension: A Doppler Imaging Study

    Directory of Open Access Journals (Sweden)

    Huan Zheng

    2011-01-01

    Full Text Available Objective. To study the effects of 6 months’ exercise training on ventricular function in hypertensive patients. Methods. Both groups received routine anti-hypertensive pharmacological therapy and one received a 6 months’ exercise program in addition. All patients underwent incremental cardiopulmonary exercise test and echocardiography in baseline and after 6 months. Results. (1 In 6 months’ follow-up, PeakVO2, Powermax (max workload, AT (anaerobic threshold, VO2AT (VO2 at anaerobic threshold, tAT (time from beginning to anaerobic threshold (<.05, were increased in the exercise group. HRrest (Heart rate at rest was decreased (<.05. LAVI (left atrial volume index, peak mitral filling velocities during early (E and late (A diastole E/A ratio, DT(deceleration time of the mitral E wave, IVST(Interventricular septum thickness in diastole, tissue Doppler indice Mean Ea/Aa ratio (<.05 were also improved. (2 Correlation analysis: 4 variates had significant effect on change of PeakVO2 in the exercise group: age (=−0.39, change of HRrest (=0.59, change of E/A (=0.55, change of Mean Ea/Aa (=0.58; Through analyzing 2 groups patients’ baseline values, their age (=−0.32, VO2AT (=0.29, HRrest (=−0.25, LAVI (=−0.24, E/A (=0.41 were found to be independent predictors of MeanEa/Aa. -value under .05 was considered statistically significant. Conclusion. 6 months’ exercise could enhance hypertensive patients’ aerobic exercise level and diastolic function to a certain extent.

  4. Effect of ivabradine on left ventricular remodelling after reperfused myocardial infarction: A pilot study.

    Science.gov (United States)

    Gerbaud, Edouard; Montaudon, Michel; Chasseriaud, Warren; Gilbert, Stephen; Cochet, Hubert; Pucheu, Yann; Horovitz, Alice; Bonnet, Jacques; Douard, Hervé; Coste, Pierre

    2014-01-01

    Heart rate is a major determinant of myocardial oxygen demand; in ST-segment elevation myocardial infarction (STEMI), patients treated with primary percutaneous intervention (PPCI), heart rate at discharge correlates with mortality. Ivabradine is a pure heart rate-reducing agent that has no effect on blood pressure and contractility, and can reverse left ventricular (LV) remodelling in patients with heart failure. To evaluate whether ivabradine, when added to current guideline-based therapy, improves LV remodelling in STEMI patients treated with PPCI. This paired-cohort study included 124 patients between June 2011 and July 2012. Ivabradine (5mg twice daily) was given promptly after PPCI, along with beta-blockers, to obtain a heart rate<60 beats per minute (ivabradine group). This group was matched with STEMI patients treated in line with current guidelines, including beta-blockers (bisoprolol), according to age, sex, infarct-related coronary artery, ischaemia time and infarct size determined by initial cardiac magnetic resonance imaging (CMR) (control group). Statistical analyses were performed according to an intention-to-continue treatment principle. CMR data at 3 months were available for 122 patients. Heart rate was lower in the ivabradine group than in the control group during the initial CMR (P=0.02) and the follow-up CMR (P=0.006). At the follow-up CMR, there was a smaller increase in LV end-diastolic volume index in the ivabradine group than in the control group (P=0.04). LV end-systolic volume index remained unchanged in the ivabradine group, but increased in the control group (P=0.01). There was a significant improvement in LV ejection fraction in the ivabradine group compared with in the control group (P=0.04). In successfully reperfused STEMI patients, ivabradine may improve LV remodelling when added to current guideline-based therapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Reference curve of the fetal ventricular septum area by the STIC method: preliminary study.

    Science.gov (United States)

    Rolo, Liliam Cristine; Marcondes Machado Nardozza, Luciano; Araujo Júnior, Edward; Simioni, Christiane; Maccagnano Zamith, Marina; Fernandes Moron, Antonio

    2011-05-01

    Early detection of septal changes such as septal hypertrophy commonly present in fetuses of diabetic mothers would help reduce the high rates of infant mortality. Determine reference ranges for the fetal ventricular septal area through three-dimensional ultrasound (US3D) using the STIC method (Spatio-Temporal Image Correlation). We conducted a cross-sectional study with 69 pregnant women between the 18th and 33rd weeks of pregnancy. We used as a reference the four-chamber plane with the ROI (Region of Interest) positioned from the ventricles; the septum area were manually marked. To assess the correlation of the interventricular septum area with gestational age (GA), we constructed scatter plots and calculated Pearson's correlation coefficient (r), and the adjustment was performed by the coefficient of determination (R²). We calculated averages, medians, standard deviations (sd), as well as maximum and minimum values. To calculate the intraobserver reproducibility, we used the intraclass correlation coefficient (ICC). The interventricular septum thickness was measured and it was correlated with gestational age and the septal area rendered in 52 patients using the ICC. The interventricular septum area was highly correlated with gestational age (r = 0.81), and the average increased from 0.47 cm² in the 18th week to 2.42 cm² in the 33rd of gestation. The intraobserver reproducibility was excellent with ICC = 0.994. No significant correlation was observed between the interventricular septum measurement and the GA (R² = 0.200), as well as there was no correlation with the septal area rendered with ICC = 0.150. Reference intervals for the interventricular septum area between the 18th and the 33rd pregnancy week were determined to be highly reproducible.

  6. Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study.

    Science.gov (United States)

    Jimenez, David; Nieto, Rosa; Corres, Jesús; Fernández-Golfín, Covadonga; Barrios, Deisy; Morillo, Raquel; Quezada, Carlos Andres; Huisman, Menno; Yusen, Roger D; Kline, Jeffrey

    2018-02-01

    The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction. We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75mg in the first 24h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter>30mm in the parasternal window; ii) RV diameter>left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure>30mmHg. Persistence of RV dysfunction at 48h and 7days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7days after randomization. Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48h in 59% (95% confidence interval [CI], 33-82%) of the diclofenac group and in 76% (95% CI, 50-93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], -17 percentage points; 95% CI, -47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2-29%) of patient in the placebo group. Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE. URL: http://www.clinicaltrials.gov. Unique identifier: NCT

  7. Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study.

    Science.gov (United States)

    Aaron, Carrie P; Hoffman, Eric A; Lima, Joao A C; Kawut, Steven M; Bertoni, Alain G; Vogel-Claussen, Jens; Habibi, Mohammadali; Hueper, Katja; Jacobs, David R; Kalhan, Ravi; Michos, Erin D; Post, Wendy S; Prince, Martin R; Smith, Benjamin M; Ambale-Venkatesh, Bharath; Liu, Chia-Ying; Zemrak, Filip; Watson, Karol E; Budoff, Matthew; Bluemke, David A; Barr, R Graham

    2017-01-01

    Evaluation of impaired left ventricular (LV) filling has focused on intrinsic causes of LV dysfunction; however, pulmonary vascular changes may contribute to reduced LV filling and dyspnea. We hypothesized that lower total pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated with dyspnea and decrements in LV end-diastolic volume, particularly among ever-smokers. The Multi-Ethnic Study of Atherosclerosis recruited adults without clinical cardiovascular disease in 2000-02. In 2010-12, TPVV was ascertained as the volume of arteries and veins in the lungs detectable on non-contrast chest CT (vessels ≥1 mm diameter). Cardiac measures were assessed by magnetic resonance imaging (MRI). Dyspnea was self-reported. Of 2303 participants, 53% had ever smoked cigarettes. Among ever-smokers, a lower TPVV was associated with a lower LV end-diastolic volume (6.9 mL per SD TPVV), stroke volume, and cardiac output and with dyspnea (all P-values lung disease and those with 0-10 pack-years but were mostly non-significant among never-smokers. TPVV was associated smaller left atrial volume but not with LV ejection fraction or MRI measures of impaired LV relaxation. In a second sample of ever-smokers, a lower pulmonary microvascular blood volume on contrast-enhanced MRI was also associated with a lower LV end-diastolic volume (P-value = 0.008). Reductions in pulmonary vascular volume were associated with lower LV filling and dyspnea among ever-smokers, including those without lung disease, suggesting that smoking-related pulmonary vascular changes may contribute to symptoms and impair cardiac filling and function without evidence of impaired LV relaxation.

  8. Left ventricular noncompaction in an infant: use of non-ECG-gated cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Department of Radiology, Asan Medical Center and Research Institute of Radiology, Songpa-gu, Seoul (Korea); Park, In-Sook [University of Ulsan College of Medicine, Department of Pediatric Cardiology, Asan Medical Center, Seoul (Korea)

    2007-02-15

    We report an infant who had left ventricular dysfunction of unknown etiology and was diagnosed with left ventricular noncompaction by non-ECG-gated cardiac CT. This relatively rare diagnosis, an unclassified cardiomyopathy, was confirmed by retrospective review of echocardiography on which the diagnosis had initially been missed. As in echocardiography, CT was capable of delineating the characteristic two-layered myocardium of the left ventricle with the most severe involvement of the apical segment. (orig.)

  9. Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study.

    Directory of Open Access Journals (Sweden)

    José T Ortiz-Pérez

    Full Text Available Angiotensin-converting enzyme 2 (ACE2 cleaves Angiotensin-II to Angiotensin-(1-7, a cardioprotective peptide. Serum soluble ACE2 (sACE2 activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI. A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4-134.8] vs 74.9 [62.8-87.5] RFU/µl/hr, p<0.001. At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9-168.6] RFU/µl/hr, p<0.01. An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = -0.519, p<0.001; r = -0.453, p = 0.001, respectively. Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001. Both, infarct size (β = -0.470 [95%CI:-0.691:-0.248], p<0.001 and sACE2 at 7 days (β = -0.025 [95%CI:-0.048:-0.002], p = 0.030 were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027. In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling.

  10. Long-Term Regulation of the Local Renin-Angiotensin System in the Myocardium of Spontaneously Hypertensive Rats by Feeding Bioactive Peptides Derived from Spirulina platensis.

    Science.gov (United States)

    Pan, Huanglei; She, Xingxing; Wu, Hongli; Ma, Jun; Ren, Difeng; Lu, Jun

    2015-09-09

    This study investigated the long-term (8 weeks) anti-hypertensive effects of 10 mg/kg tripeptides isolated from Spirulina platensis, Ile-Gln-Pro (IQP) and Val-Glu-Pro (VEP), and S. platensis hydrolysates (SH) on spontaneously hypertensive rats. The treatment period was 6 weeks, and observation continued for another 2 weeks. After treatment, weighted systolic blood pressure, weighted diastolic blood pressure, left ventricular mass index, and right ventricular mass index of groups treated with IQP, VEP, and SH were significantly lower than those of the group treated with distilled water, even when the treatments had been withdrawn for 2 weeks. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting showed the mRNA expression levels and protein/peptide concentrations of the main components of the renin angiotensin system in myocardium were significantly affected by treatment: angiotensin converting enzyme, angiotensin II, and angiotensin type 1 receptor were down-regulated, whereas angiotensin type 2 receptor, angiotensin converting enzyme 2, angiotensin-(1-7), and Mas receptor were up-regulated.

  11. Neuroradiological findings and clinical features of fourth-ventricular meningioma: A study of 10 cases

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, B.-Y.; Yin, B.; Li, Y.-X. [Department of Radiology, Huashan Hospital, Fudan University, Shanghai (China); Wu, J.-S. [Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai (China); Chen, H. [Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai (China); Wang, X.-Q., E-mail: wangxq10@126.com [Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai (China); Geng Daoyng, E-mail: fdhsgdy@126.com [Department of Radiology, Huashan Hospital, Fudan University, Shanghai (China)

    2012-05-15

    Aim: To present the neuroradiological and clinical findings of fourth-ventricular meningiomas to increase awareness of this entity. Materials and methods: The computed tomography (CT; n = 5), magnetic resonance imaging (MRI; n = 9) features and clinical presentations of 10 patients with pathologically documented fourth-ventricular meningiomas were retrospectively analysed. Results: All tumours appeared as well-demarcated masses in the fourth ventricle at CT and MRI. The tumour shape was round in eight cases (80%) and irregular in two cases (20%). The CT images of five cases showed predominantly isoattenuation in three cases and high attenuation in two cases, with a mean attenuation value of 52 HU. In addition, calcifications were seen in three cases. At MRI, nine masses were isointense (n = 6) or hypointense (n = 3) to grey matter on T1-weighted images and mildly hyperintense (n = 4), isointense (n = 3), hypointense (n = 1), and of mixed signal intensity (n = 1) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Signal voids were visible in two cases. Enhancement after injection of contrast material was marked homogeneous (n = 5) or heterogeneous (n = 5) on CT or T1-weighted images. Three tumours had mild peritumoural oedema. Three tumours were associated with obstructive hydrocephalus. The pathological subtype of the 10 meningiomas was fibromatous (n = 5), atypical (n = 2), and one each of transitional, psammomatous, and clear-cell type. Conclusion: Although fourth-ventricular meningioma is quite rare, it should be considered in differential diagnosis of neoplasms within the fourth ventricle. The relatively typical radiological appearance, combined the age and sex of patients, can suggest the diagnosis of fourth-ventricular meningioma.

  12. In vivo selective binding of (R)-[{sup 11}C]rolipram to phosphodiesterase-4 provides the basis for studying intracellular cAMP signaling in the myocardium and other peripheral tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kenk, Miran [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Greene, Michael [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Thackeray, James [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Kemp, Robert A. de [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Lortie, Mireille [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Thorn, Stephanie [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Beanlands, Rob S. [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); DaSilva, Jean N. [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada) and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada)]. E-mail: jdasilva@ottawaheart.ca

    2007-01-15

    Introduction: Phosphodiesterase-4 (PDE4) enzymes specifically break down the second messenger cAMP, thereby terminating the intracellular signaling cascade that plays an essential role in neurohormonal modulation of many physiological systems. PDE4 activity and expression are regulated by cAMP levels, suggesting that measurement of PDE4 provides an index of intracellular cAMP signaling. Methods: Male Sprague-Dawley rats were administered (R)- or the less active enantiomer (S)-[{sup 11}C]rolipram and sacrificed 30 min later with tracer retention measured in various tissues. Co-injections with saturating doses of unlabeled (R)-rolipram (S)-rolipram and Ro 20-1724, as well as subtype-selective PDE inhibitors vinpocetine, Bay 60-7550, cilostazol and zaprinast were used to establish binding selectivity for PDE4 over PDE1, PDE2, PDE3 and PDE5 subtypes, respectively. Autoradiography was performed to substantiate results of biodistribution studies in the myocardium. Results: In vivo (R)-[{sup 11}C]rolipram retention was dose-dependently reduced by co-injections of (R)-rolipram and (S)-rolipram (ED{sub 50} values of 0.03 mg/kg and 0.2 mg/kg, respectively). Vinpocetine, Bay 60-7550, cilostazol and zaprinast had no effect on (R)-[{sup 11}C]rolipram binding, while (R)-rolipram and Ro 20-1724 reduced the tracer uptake to nonspecific levels in PDE4-rich tissues. Conclusions: In addition to the brain (R)-[{sup 11}C]rolipram binds selectively to PDE4 across all cardiac regions, skeletal muscle, lungs and pancreas, but not in the adipose tissues. In vivo findings were confirmed by in vitro autoradiography studies, suggesting that (R)-[{sup 11}C]rolipram can be applied to evaluate alterations in central and peripheral PDE4 levels and cAMP-mediated signaling.

  13. Compatibility of Astragalus and Salvia extract inhibits myocardial fibrosis and ventricular remodeling by regulation of protein kinase D1 protein

    Science.gov (United States)

    Mao, Bingyu; Nuan, Liu; Yang, Lei; Zeng, Xiaotao

    2015-01-01

    Aims: This study is to determine the effect of astragalus and salvia extract on the alteration of myocardium in a rat model of myocardial infarction. Methods: A total of 40 male Sprague-Dawley rats were randomly divided into the sham-operated group, the control group, the Astragalus group, the Salvia group, and the compatibility of Astragalus and Salvia and group. The cardiac functions were determined at 8 weeks after treatment. Hematoxylin-eosin staining was performed to observe the morphology and arrangement of cardiomyocytes. Masson’s trichrome staining was performed to investigate the distribution of myocardial interstitial collagen. Immunohistochemical staining was performed to determine the expression ofprotein kinase D1 in myocardial tissues. Results: In the sham-operated group, the Astragalus group, the Salvia group, and the compatibility of Astragalus and Salvia group, the left ventricular systolic pressure and the maximum rate of left ventricular pressure were significantly increased while the left ventricular end diastolic pressure were significantly decreased when compared with those in the control group (P Salvia group. Contents of collagen fibers in myocardial tissues were decreased in the compatibility of Astragalus and Salvia group (P Salvia group. Conclusions: Compatibility of Astragalus and Salvia extract may inhibit myocardial fibrosis and ventricular remodeling by regulation of protein kinase D1 protein in a rat model of myocardial infarction. PMID:26064267

  14. Protective effect of curcumin against myocardium injury in ischemia reperfusion rats.

    Science.gov (United States)

    Liu, HuaJin; Wang, ChangHua; Qiao, Zengyong; Xu, Yawei

    2017-12-01

    Curcumin has long been used as a condiment and a traditional medicine worldwide. The current study investigates the possible protective effect of curcumin on heart function in myocardium ischemia-reperfusion (MIR) rats. We fed Sprague-Dawley (SD) rats (10 in each group) either curcumin (10, 20 or 30 mg/kg/d) or saline. Twenty days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (60 min), and subsequently, the heart (3 h) reperfused by releasing the ligation. Then, lipid profile, lipid peroxidation products, antioxidant enzymes and gene expression were assessed in myocardium tissue. Only the rats that were supplemented with curcumin (10, 20 or 30 mg/kg/d) showed significant (p myocardium apoptosis.

  15. Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats.

    Science.gov (United States)

    Ma, Jiangwei; Qiao, Zengyong; Xu, Biao

    2013-10-01

    The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.

  16. Temporary epicardial cardiac resynchronisation versus conventional right ventricular pacing after cardiac surgery: study protocol for a randomised control trial

    Directory of Open Access Journals (Sweden)

    Russell Stuart J

    2012-02-01

    Full Text Available Abstract Background Heart failure patients with stable angina, acute coronary syndromes and valvular heart disease may benefit from revascularisation and/or valve surgery. However, the mortality rate is increased- 5-30%. Biventricular pacing using temporary epicardial wires after surgery is a potential mechanism to improve cardiac function and clinical endpoints. Method/design A multi-centred, prospective, randomised, single-blinded, intervention-control trial of temporary biventricular pacing versus standard pacing. Patients with ischaemic cardiomyopathy, valvular heart disease or both, an ejection fraction ≤ 35% and a conventional indication for cardiac surgery will be recruited from 2 cardiac centres. Baseline investigations will include: an electrocardiogram to confirm sinus rhythm and measure QRS duration; echocardiogram to evaluate left ventricular function and markers of mechanical dyssynchrony; dobutamine echocardiogram for viability and blood tests for renal function and biomarkers of myocardial injury- troponin T and brain naturetic peptide. Blood tests will be repeated at 18, 48 and 72 hours. The principal exclusions will be subjects with permanent atrial arrhythmias, permanent pacemakers, infective endocarditis or end-stage renal disease. After surgery, temporary pacing wires will be attached to the postero-lateral wall of the left ventricle, the right atrium and right ventricle and connected to a triple chamber temporary pacemaker. Subjects will be randomised to receive either temporary biventricular pacing or standard pacing (atrial inhibited pacing or atrial-synchronous right ventricular pacing for 48 hours. The primary endpoint will be the duration of level 3 care. In brief, this is the requirement for invasive ventilation, multi-organ support or more than one inotrope/vasoconstrictor. Haemodynamic studies will be performed at baseline, 6, 18 and 24 hours after surgery using a pulmonary arterial catheter. Measurements will be

  17. Nonischemic left ventricular scar and cardiac sudden death in the young.

    Science.gov (United States)

    di Gioia, Cira R T; Giordano, Carla; Cerbelli, Bruna; Pisano, Annalinda; Perli, Elena; De Dominicis, Enrico; Poscolieri, Barbara; Palmieri, Vincenzo; Ciallella, Costantino; Zeppilli, Paolo; d'Amati, Giulia

    2016-12-01

    Nonischemic left ventricular scar (NLVS) is a pattern of myocardial injury characterized by midventricular and/or subepicardial gadolinium hyperenhancement at cardiac magnetic resonance, in absence of significant coronary artery disease. We aimed to evaluate the prevalence of NLVS in juvenile sudden cardiac death and to ascertain its etiology at autopsy. We examined 281 consecutive cases of sudden death of subjects aged 1 to 35 years. NLVS was defined as a thin, gray rim of subepicardial and/or midmyocardial scar in the left ventricular free wall and/or the septum, in absence of significant stenosis of coronary arteries. NLVS was the most frequent finding (25%) in sudden deaths occurring during sports. Myocardial scar was localized most frequently within the left ventricular posterior wall and affected the subepicardial myocardium, often extending to the midventricular layer. On histology, it consisted of fibrous or fibroadipose tissue. Right ventricular involvement was always present. Patchy lymphocytic infiltrates were frequent. Genetic and molecular analyses clarified the etiology of NLVS in a subset of cases. Electrocardiographic (ECG) recordings were available in more than half of subjects. The most frequent abnormality was the presence of low QRS voltages (<0.5 mV) in limb leads. In serial ECG tracings, the decrease in QRS voltages appeared, in some way, progressive. NLVS is the most frequent morphologic substrate of juvenile cardiac sudden death in sports. It can be suspected based on ECG findings. Autopsy study and clinical screening of family members are required to differentiate between arrhythmogenic right ventricular cardiomyopathy/dysplasia and chronic acquired myocarditis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Metastatic Midgut Carcinoid in the Myocardium.

    Science.gov (United States)

    Bukowczan, Jakub; Lois, Konstantinos B; Skinner, Jane; Petrides, George; James, Robert Andrew; Perros, Petros

    2015-09-01

    Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

  19. Assessment of inflammation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

    NARCIS (Netherlands)

    Campian, Maria E.; Verberne, Hein J.; Hardziyenka, Maxim; de Groot, Elisabeth A. A.; van Moerkerken, Astrid F.; van Eck-Smit, Berthe L. F.; Tan, Hanno L.

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a myocardial disease that predominantly affects the right ventricle (RV). Its hallmark feature is fibro-fatty replacement of RV myocardium. However, patchy inflammatory infiltrates in the RV are also consistently reported using

  20. Bi-ventricular finite element model of right ventricle overload in the healthy rat heart.

    Science.gov (United States)

    Masithulela, Fulufhelo

    2016-11-25

    The recognition of RV overpressure is critical to human life, as this may signify morbidity and mortality. Right ventricle (RV) dysfunction is understood to have an impact on the performance of the left ventricle (LV), but the mechanisms remain poorly understood. It is understood that ventricular compliance has the ability to affect cardiac performance. In this study, a bi-ventricular model of the rat heart was used in preference to other, single-ventricle models. Finite element analysis (FEA) of the bi-ventricular model provides important information on the function of the healthy heart. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material using finite element (FE) methods. Bi-ventricular geometries of healthy rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. In simulating the normal passive filling of the rat heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the LV and RV respectively. In addition, to simulate the overpressure of the RV, pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV and RV respectively. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. The results show that the average circumferential stress at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on the endocardium of the over pressured and healthy model respectively. The average circumferential stress at the epicardium, mid-wall and endocardium in the case of a normal heart is 10 times lower than in the overloaded heart model. The finite analysis method is able to provide

  1. Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study.

    Science.gov (United States)

    Appiah, Duke; Schreiner, Pamela J; Gunderson, Erica P; Konety, Suma H; Jacobs, David R; Nwabuo, Chike C; Ebong, Imo A; Whitham, Hilary K; Goff, David C; Lima, Joao A; Ku, Ivy A; Gidding, Samuel S

    2016-03-01

    Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk. We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990-1991 (mean age 28.8 years) and 2010-2011. During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (-15.0 vs. -15.7%, P = 0.025), circumferential peak strain (-14.8 vs. -15.6%, P = 0.028), lateral e' wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e' wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010-2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m(2), P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations. Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Mediterranean diet score and left ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Levitan, Emily B; Ahmed, Ali; Arnett, Donna K; Polak, Joseph F; Hundley, W Gregory; Bluemke, David A; Heckbert, Susan R; Jacobs, David R; Nettleton, Jennifer A

    2016-09-01

    Data are limited on the relation between dietary patterns and left ventricular (LV) structure and function. We examined cross-sectional associations of a diet-score assessment of a Mediterranean dietary pattern with LV mass, volume, mass-to-volume ratio, stroke volume, and ejection fraction. We measured LV variables with the use of cardiac MRI in 4497 participants in the Multi-Ethnic Study of Atherosclerosis study who were aged 45-84 y and without clinical cardiovascular disease. We calculated a Mediterranean diet score from intakes of fruit, vegetables, nuts, legumes, whole grains, fish, red meat, the monounsaturated fat:saturated fat ratio, and alcohol that were self-reported with the use of a food-frequency questionnaire. We used linear regression with adjustment for body size, physical activity, and cardiovascular disease risk factors to model associations and assess the shape of these associations (linear or quadratic). The Mediterranean diet score had a slight U-shaped association with LV mass (adjusted means: 146, 145, 146, and 147 g across quartiles of diet score, respectively; P-quadratic trend = 0.04). The score was linearly associated with LV volume, stroke volume, and ejection fraction: for each +1-U difference in score, LV volume was 0.4 mL higher (95% CI: 0.0, 0.8 mL higher), the stroke volume was 0.5 mL higher (95% CI: 0.2, 0.8 mL higher), and the ejection fraction was 0.2 percentage points higher (95% CI: 0.1, 0.3 percentage points higher). The score was not associated with the mass-to-volume ratio. A higher Mediterranean diet score is cross-sectionally associated with a higher LV mass, which is balanced by a higher LV volume as well as a higher ejection fraction and stroke volume. Participants in this healthy, multiethnic sample whose dietary patterns most closely conformed to a Mediterranean-type pattern had a modestly better LV structure and function than did participants with less-Mediterranean-like dietary patterns. This trial was registered at

  3. Multielectrode vs. point-by-point mapping for ventricular tachycardia substrate ablation: a randomized study.

    Science.gov (United States)

    Acosta, Juan; Penela, Diego; Andreu, David; Cabrera, Mario; Carlosena, Alicia; Vassanelli, Francesca; Alarcón, Francisco; Soto-Iglesias, David; Korshunov, Viatcheslav; Borras, Roger; Linhart, Markus; Martínez, Mikel; Fernández-Armenta, Juan; Mont, Lluis; Berruezo, Antonio

    2017-01-08

    Ventricular tachycardia (VT) substrate ablation is based on detailed electroanatomical maps (EAM). This study analyses whether high-density multielectrode mapping (MEM) is superior to conventional point-by-point mapping (PPM) in guiding VT substrate ablation procedures. This was a randomized controlled study (NCT02083016). Twenty consecutive ischemic patients undergoing VT substrate ablation were randomized to either group A [n = 10; substrate mapping performed first by PPM (Navistar) and secondly by MEM (PentaRay) ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM ablation guided by MEM]. Ablation was performed according to the scar-dechanneling technique. Late potential (LP) pairs were defined as a Navistar-LP and a PentaRay-LP located within a three-dimensional distance of ≤ 3 mm. Data obtained from EAM, procedure time, radiofrequency time, and post-ablation VT inducibility were compared between groups. Larger bipolar scar areas were obtained with MEM (55.7±31.7 vs. 50.5±26.6 cm(2); P = 0.017). Substrate mapping time was similar with MEM (19.7±7.9 minutes) and PPM (25±9.2 minutes); P = 0.222. No differences were observed in the number of LPs identified within the scar by MEM vs. PPM (73±50 vs. 76±52 LPs per patient, respectively; P = 0.965). A total of 1104 LP pairs were analysed. Using PentaRay, far-field/LP ratio was significantly lower (0.58±0.4 vs. 1.64±1.1; P = 0.01) and radiofrequency time was shorter [median (interquartile range) 12 (7-20) vs. 22 (17-33) minutes; P = 0.023]. No differences were observed in VT inducibility after procedure. MEM with PentaRay catheter provided better discrimination of LPs due to a lower sensitivity for far-field signals. Ablation guided by MEM was associated with a shorter radiofrequency time. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email

  4. The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population

    NARCIS (Netherlands)

    Ferrari, R.; Ford, I.; Fox, K.; Steg, P. G.; Tendera, M.; Cohen Arazi, H.; Nul, D. R.; Ahuad Guerrero, R. A.; Luciardi, H. L.; Sinisi, V. A.; Perna, E. R.; Schygiel, P. O.; Sanjurjo, M. S.; Fernandez, A. A.; del Valle Lobo Marquez, L. L.; Fuselli, J. J.; Hasbani, E.; Ibañez, J. O.; Cartasegna, L. R.; Lembo, L. A.; Thierer, J.; Varini, S.; Buscema, J. J.; Orlandini, A. D.; Bustos, B.; Guzmán, L. A.; Luquez, H. A.; Amuchastegui, M.; Allall, O. A.; Iglesias, R. M.; Sokn, F. J.; Montaña, O. R.; Sanchez, A.; Vogel, D.; Eber, B.; Huber, K.; Lang, I.; Pichler, A. N.; Dendale, P. A. C.; Vanderheyden, M.; van Mieghem, W.; Chenu, P.; Friart, A.; Missault, L.; Vachiery, J. L.; Materne, P.; François, B. A. A.; Sirakova, V.; Penkov, N.; Georgiev, B.; Grigorov, M.; Taseva, T.; Nachev, C.; Guenova, D.; Perchev, I.; Denchev, S.; Donova, T.; Torbova, S.; Goudev, A.; Raev, D.; Gotchev, D.; Tzekova, M.; Chompalova, B.; Hergeldjieva, V.; Kamenova, Z.; Dzhurzdhev, A.; Tardif, J. C.; Talbot, P.; Yao, L.; Ma, P.; Constance, C.; Bernstein, V.; Heath, J.; Lalani, A.; Haddad, H.; To, T. B.; Pandey, S.; Desrochers, D.; Fortin, C.; Poirier, P.; Savard, D.; Baird, M.; Lonn, E.; Coutu, B.; Vertes, G. E.; Rebane, T.; Kouz, S.; Raco, D.; Rajda, M.; Parker, J. O.; Glanz, A.; Lepage, S.; Parker, J. D.; Klinke, W. P.; Rupka, D.; Hill, L. L.; Nawaz, S.; Chehayeb, R.; Lauzon, C.; Matangi, M.; Syan, G. S.; Hu, D.; Lv, S.; Yan, X.; Gai, L.; Ge, J. B.; Dong, Y.; Sun, Y.; Yuan, Z.; Zhang, F.; Wang, X.; Wang, W.; Hradec, J.; Florian, J.; Sulda, M.; Spinar, J.; Fábik, L.; Stípal, R.; Kaislerová, M.; Vitovec, J.; Vojtísek, P.; Krejcova, H.; Maratka, T.; Sochor, K.; Marcinek, G.; Povolný, J.; Jerábek, O.; Karetová, D.; Vojacek, J.; Lavicka, V.; Vencour, D.; Kotík, L.; Kuchar, J.; Drazka, J.; Penicka, M.; Kryza, R.; Soucek, M.; Ballek, L.; Spacek, R.; Brønnum Schou, J.; Torp-Pedersen, C.; Nielsen, T.; Markenvard, J.; Tuxen, C.; Hildebrandt, P.; Sejersen, H.; Rokkedal, J.; Ralfkiaer, N.; Agner, E.; Skagen, K.; Roseva Nielsen, N.; Vigholt, E.; Dodt, K. K.; Lind Rasmussen, L.; Pedersen, L.; Stentebjerg, S. E.; Asklund, M.; Klarlund, K.; Haghfelt, T.; Gøtzsche, L.; Rickers, H.; Køber, L.; Jensen, G.; Dahlstrøm, C. G.; Gøtzsche, O.; Egstrup, K.; Petersen, J.; Larsen, J.; McNair, A.; Jakobsen, T.; Larsen, C. T.; Eha, J.; Vahula, V.; Averina, O.; Viigimaa, M.; Sildmäe, S.; Kolbassova, O.; Melin, J.; Peuhkurinen, K.; Harjola, V. P.; Luoma, J.; Ovize, M.; Sellier, P.; Barthelemy, J. C.; Beaune, J.; Magnin, D.; Dambrine, P.; Khalife, K.; Wolf, J. E.; Roudaut, R.; Gabrovescu, M.; Dubois-Rande, J. L.; Galinier, M.; Genest, M.; Mansourati, J.; Aliot, E.; Carlioz, R.; Cherbi, C.; Slama, M.; Colin, P.; Decoulx, E.; Escande, M.; Fournier, P. Y.; Galley, D.; Khanoyan, P.; Jaboureck, O.; Leborgne, L.; Mann, H.; Pierre-Justin, E.; Roynard, J. L.; Soto, F. X.; Bourdon, A.; Bauer, F.; Belin, A.; Boudahne, A.; Bouvier, J. M.; Chati, Z.; Chevalier, J. M.; Chevrier, J.; Doucet, B.; Drawin, T.; Mansour, N. El; Funck, F.; Godenir, J. P.; Guillot, J. P.; Gully, C.; Habib, G.; Kahn, J. C.; Koenig, A.; Martelet, M.; Matina, D.; Gay, A.; Meurice, T.; Perret, T.; Riou, A.; Thisse, J. Y.; Demarcq, J. M.; Bodur, G.; Claudon, O.; Lemoine, C.; Roul, G.; Olive, T. G.; Huyghe de Mahenge, A.; Meinertz, T.; Baumann, G.; Böhm, M.; Cieslinski, G.; Figulla, H. R.; Gonska, B. D.; Hasenfuss, G.; Heckel, D.; Hoppe, U.; Katus, H.; Kombächer, H. D.; Müller, O.; Münzel, T.; Nienaber, C.; Oeff, M.; Rupprecht, H. J.; von Schacky, C.; Schmidt, J.; Schreckenberg, A.; Schuler, G.; Schultheiss, H. P.; Seidl, K.; Steindorf, J.; Strasser, R.; Werdan, K.; Hengstenberg, C.; Haverkamp, W.; Windstetter, U.; Al-Zoebi, A.; Pötsch, T.; Proskynitopoulos, N.; Baar, M.; Winkelmann, B. R.; Jeserich, M.; Tammen, A.; Appel, K. F.; Fries, P.; Ammer, K.; Droese, A. N.; Bergmann, K.; Bott, J.; Lange, R.; Taggeselle, J.; Rummel, R.; Kleinertz, K.; Deissner, M.; Drescher, T.; Zahorsky, R.; Schenkenberger, I.; Grooterorst, P.; Frick, H. M.; Spengler, U.; Jahnke, N.; Bauknecht, C.; Lehmann, G.; Spanier, C.; Wolde, C. H.; Natour, M.; Bosch, R.; Rüdell, U.; Gola, G.; Hering, R.; Heuer, H.; Gärtner, J.; Vardas, P.; Kremastinos, D.; Anastasiou-Nana, M.; Kallikazaros, I.; Theodorakis, G.; Kyriakides, Z.; Pyrgakis, V. N.; Siogas, K.; Kapordelis, C.; Apostolou, T.; Karvounis, H.; Papadopoulos, C.; Tziakas, D.; Tryposkiadis, F.; Koliopoulos, N.; Alexopoulos, D.; Fotiadis, I.; Kolettis, T.; Manolis, A.; Pras, A.; Lee, K.; Borbola, J.; Préda, U.; Tomcsányi, J.; Edes, I.; Nagy, A.; Lippai, J.; Regos, L.; Tóth, K.; Takács, J.; Cziráki, A.; Matoltsy, A.; Sidó, Z.; Nagy, L.; Nyárádi, A.; Mohay, A.; Rumi, G.; Polgár, P.; Zámolyi, K.; Tahy, A.; Piros, G.; Veress, G.; Barsi, B.; Kovács, A.; Sereg, M.; Pálinkás, A.; Sármán, P.; Juhász, A.; Mohácsi, A.; Harmati, L.; Lupkovics, G.; Dézsi, C. A.; Nagy, K.; Vegh, G.; Váradi, A.; Farsang, C.; Lakatos, F.; Barton, J.; Crean, P.; Foley, D.; Daly, K.; de Luca, I.; Urbinati, S.; Zanetta, M.; Porcu, M.; Cocchieri, M.; Buia, E.; Minneci, C.; Leghissa, R.; Della Cassa, S.; Pizzimenti, G.; Ingrilli, F.; Fuscaldo, G.; Bellone, E.; Pulitano, G.; Santini, M.; Uguccioni, M.; Carbonieri, E.; Barbuzzi, S.; Alberti, E.; Proto, C.; Pettinati, G.; Cosmi, F.; Colombo, A.; de Cristofaro, M.; Ambrosio, G.; Maresta, A.; de Matteis, C.; Mos, L.; Giustiniani, S.; Paparoni, S.; Proietti, G.; Giannuzzi, P.; Cardona, N.; Perna, B.; Gavazzi, A.; Capucci, A.; Reggianini, L.; Zanini, R.; Keisa, M.; Erglis, A.; Ozolina, M. A.; Gersamija, A.; Gailiss, E.; Volans, E.; Stoma, M.; Libins, A.; Grabauskiene, V.; Petrulioniene, Z.; Berukstis, E.; Kibarskis, A.; Zaliunas, R.; Marcinkeviciene, J.; Naudziunas, A.; Kirkutis, A.; Varoneckas, G.; Cornel, J. H.; Hamer, B. J. B.; Hoedemaker, G.; van den Berg, B. J.; Somer, S. T.; van der Veen, M.; van Rossum, P.; Bartels, G. L.; van Vlies, B.; Lionarons, R. J.; Dijkgraaf, R.; Wesdorp, J. C. L.; Kragten, J. A.; Fast, J.; de Milliano, P. A. R.; van Rugge, F. P.; Hoogslag, P. A. M.; Göbel, E. J. A.; Leenders, C. M.; van der Heijden, R.; Swart, H.; van Beek, G. J.; van der Zwaan, C.; Holwerda, N. J.; Winter, J. B.; Galema, T. W.; Voors, A. A.; Kirkels, J. H.; Jaarsma, W.; Zwart, P. A. G.; Thijssen, H.; Linssen, G. C. M.; Verheul, J. A.; Maas, A. H. E. M.; Willems, A. R.; Nagelsmit, M. J.; Freericks, M. P.; Pinto, Y. M.; Bruning, T. A.; Michels, H. M.; Withagen, A. J. A. M.; Jap Tjoen San, W. T. J.; Robles de Medina, R.; Nierop, P. R.; Daniels, M. C. G.; van Kempen, L. H. J.; Herrman, J. P. R.; van Wijk, L. M.; Atar, D.; Myhre, E. P.; Dickstein, K.; Musial, W.; Pulkowski, G.; Sinkiewicz, W.; Kubica, J.; Janik, K.; Rynkiewicz, A.; Miekus, P.; Szpajer, M.; Zadrozna, Z.; Krzeminska-Pakula, M.; Goch, J.; Krynicki, R.; Trusz-Gluza, M.; Janion, M.; Zinka, E.; Kawecka-Jaszcz, K.; Piwowarska, W.; Piotrowski, W.; Bloch, C.; Trojnar, R.; Targonski, R.; Pluta, W.; Krzciuk, M.; Achremczyk, P.; Kuzniar, J.; Baska, J.; Ruszkowski, P.; Drozdowski, P.; Kurowski, M.; Krupa, E.; Slowinski, S.; Skura, M.; Pusz, T.; Jaworska, K.; Dluzniewski, M.; Opolski, G.; Piepiorka, M.; Andrzejak, R.; Wrabec, K.; Ponikowski, P.; Loboz-Grudzien, K.; Wodniecki, J.; Kalarus, Z.; Tracz, W.; Kozlowski, A.; Ruzyllo, W.; Mazurek, W.; Szolkiewicz, M.; Paisana Lopes, J. P.; Carvalho, N.; Teixeira, M.; Ferreira Da Silva, G.; Aguiar, J.; Lousada, N.; Salgado, A.; Providencia, L. A.; Freitas, J.; Oliveira Soares, A.; Capalneanu, R.; Macarie, C.; Bruckner, I.; Cinteza, M.; Nanea, T.; Dorobantu, M.; Vintila, M.; Dan, G. A.; Dimulescu, D. R.; Arsenescu, C.; Ionescu, D. D.; Dragulescu, I. S.; Avram, R.; Opris, M.; Manitiu, I.; Craiu, E.; Babes, K.; Tase, A.; Tintoiu, I.; Apetrei, E.; Olinic, N. C.; Radoi, M.; Minescu, B.; Tanaseanu, C. M.; Sinescu, C. J.; Tomescu, M.; Loariu, C.; Carasca, E.; Datcu, M. D.; Dumitrascu, D. L.; Ionascu-Fometescu, C. R.; Pop, C.; Radu, I.; Vladoianu, M.; Kiss, L.; Toplnitchi, L.; Aroutiounov, G. P.; Beloussov, Y. B.; Vasyuk, Y. A.; Vertkine, A. L.; Zadionchenko, V. S.; Zateyshchikov, D. A.; Ya Ivleva, A.; Karpov, Y. A.; Kisliak, O. A.; Kobalava, J. D.; Yu Konyakhin, A.; Kukes, V. G.; Yu Mareev, V.; Mkrtchyan, V. R.; Orlov, V. A.; Sidorenko, B. A.; Stryuk, R. I.; Tereschenko, S. N.; Shpektor, A. V.; Pozdnyakov, Y. M.; Khrustalev, O. A.; Yakusevich, V. V.; Yakushin, S. S.; Azarin, O. G.; Karpov, Y. B.; Moiseeva, O. M.; Perepech, N. B.; Sayganov, S. A.; Svistov, A. S.; Sorokin, L. A.; Shlyakhto, E. V.; Lopatin, Y. M.; Nedogoda, S. V.; Arkhipov, M. V.; Kuimov, A. D.; Tsyba, L. P.; Yakhontova, P. K.; Chumakova, G. A.; Barbarsh, O. L.; Bart, B. Y.; Bychkova, L.; Golukhova, E.; Zhilyaev, E. V.; Rodoman, G. V.; Rudnev, D. V.; Tankhilevich, B. M.; Shostak, N. A.; Kastanaian, A. A.; Pimenov, L. T.; Murín, J.; Kamenský, G.; Gonsorcík, J.; Bada, V.; Pella, D.; Sojka, G.; Vahala, P.; Bugán, V.; Kmec, J.; Micko, K.; Rakovec, P.; Kanic, V.; Skrabl-Mocnik, F.; Slemenik-Pusnik, C.; Melihen-Bartolic, C.; Markez, J.; Macaya de Miguel, C.; Grande, A.; Jimenez Navarro, M.; Romero Hinojosa, J. A.; Bertomeu Martinez, V.; Paz Bermejo, M. A.; Illa Gay, J.; Gusi Tragant, G.; Calvo Gomez, C.; Iglesias Cubero, G.; Balaguer Recena, J.; López García-Aranda, V.; Caparos Valderrama, J.; Iglesias Alonso, L. F.; San Román Calvar, A.; Fernanez Aviles, F.; Perez Villa, F.; Bruguera Cortada, J.; Fernandez Alvarez, R.; Noriega Peiro, F.; Calvo Iglesias, F.; Sevilla Toral, B.; López Bescós, L.; Garcia de Burgos, F.; Sola Casado, R.; Galve, E.; Casares Garcia, G.; Delborg, M.; Herlitz, J.; Ullman, B.; Blomgren, J.; Bandh, S.; Ohlin, H.; Dubach, P.; Gallino, A.; Hess, O.; Moccetti, T.; Eeckhout, E.; Vontobel, H.; Delabays, A.; Erol, K.; Kozan, O.; Mutlu, B.; Ergene, O.; Acarturk, E.; Yilmaz, H.; Ural, D.; Parkhomenko, O.; Polyvoda, S.; Dyadyk, A.; Vatutin, M.; Karpenko, O.; Kubyshkin, V.; Rudenko, L.; Putintsev, V.; Krayz, I.; Kovalsky, I.; Rudyk, Y.; Yurlov, V.; Mostovoy, Y.; Rishko, M.; Barna, O.; Slyvka, Y.; Perepelytsya, M.; Seredyuk, N.; Bazylevych, A.; Glushko, L.; Tashchuk, V.; Girina, O.; Vizir, V.; Pertseva, T.; Vlasenko, M.; Goloborodko, B.; Kolomiets, S.; Dzyak, G.; Sharuk, O.; Storozhuk, B.; Kovalenko, V.; Khomazyuk, T.; Soldatchenko, S.; Lutay, M.; Zharinov, O.; Serkova, V.; Korkushko, O.; Korzh, O.; Netyazheko, V.; Sakharchuck, I.; Stadnyuk, L.; Bereznyakov, I.; Semidotska, Z.; Kolchin, Y.; Voronkov, L.; Tseluyko, V.; Amosova, K.; Batuschkin, V.; Hall, A.; Lindsay, S.; Moriarty, A.; Kadr, H.; Francis, C. M.; Saltissi, S.; Rozkovec, A.; Groves, P.; Crook, J. R.; Purvis, J.; Brooksby, P.; Stewart, M.; Dutka, D.; Timmis, A.; Baig, M. W.; Brady, A.; Williams, S.; Brooks, N.; Greaves, K.

    2008-01-01

    OBJECTIVES: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to

  5. The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population

    DEFF Research Database (Denmark)

    NN, NN; Ferrari, R; Ford, I

    2008-01-01

    OBJECTIVES: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to e...

  6. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model.

    Science.gov (United States)

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-Ichiro; Egashira, Kensuke

    2016-01-01

    There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial

  7. Developing vasculature and stroma in engineered human myocardium.

    Science.gov (United States)

    Kreutziger, Kareen L; Muskheli, Veronica; Johnson, Pamela; Braun, Kathleen; Wight, Thomas N; Murry, Charles E

    2011-05-01

    We recently developed a scaffold-free patch of human myocardium with human embryonic stem cell-derived cardiomyocytes and showed that stromal and endothelial cells form vascular networks in vitro and improve cardiomyocyte engraftment. Here, we hypothesize that stromal cells regulate the angiogenic phenotype by modulating the extracellular matrix (ECM). Human marrow stromal cells (hMSCs) support the greatest degree of endothelial cell organization, at 1.3- to 2.4-fold higher than other stromal cells tested. Stromal cells produce abundant ECM components in patches, including fibrillar collagen, hyaluronan, and versican. We identified two clonal hMSC lines that supported endothelial networks poorly and robustly. Interestingly, the pro-angiogenic hMSCs express high levels of versican, a chondroitin sulfate proteglycan that modulates angiogenesis and wound healing, whereas poorly angiogenic hMSCs produce little versican. When transplanted onto uninjured athymic rat hearts, patches with proangiogenic hMSCs develop ~ 50-fold more human vessels and form anastomoses with the host circulation, resulting in chimeric vessels containing erythrocytes. Thus, stromal cells play a key role in supporting vascularization of engineered human myocardium. Different stromal cell types vary widely in their proangiogenic ability, likely due in part to differences in ECM synthesis. Comparison of these cells defines an in vitro predictive platform for studying vascular development.

  8. Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias

    Science.gov (United States)

    Campos, Fernando O.; Shiferaw, Yohannes; Vigmond, Edward J.; Plank, Gernot

    2017-09-01

    Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na+) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na+ current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na+ channelopathies.

  9. Free Radical Oxidation in Rat Myocardium after Maximum Permissible Hepatic Resection.

    Science.gov (United States)

    Ermolaev, P A; Khramykh, T P; Barskaya, L O

    2016-03-01

    Free radical oxidation in rat myocardial homogenate was studied by chemiluminescent assay during the early terms after maximum permissible liver resection. During this period, activation of free radical oxidation was biphasic. The critical terms characterized by dramatic intensification of free radical oxidation in the myocardium are the first hour and the first day after surgery. The period from 3 to 12 h after surgery, in which the indices of chemiluminescence decrease, can be tentatively termed as the period of "putative wellbeing". Normalization of the free radical oxidation processes in the myocardium occurred by day 7 after surgery.

  10. Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

    Science.gov (United States)

    Nordlund, David; Kanski, Mikael; Jablonowski, Robert; Koul, Sasha; Erlinge, David; Carlsson, Marcus; Engblom, Henrik; Aletras, Anthony H; Arheden, Håkan

    2017-01-30

    Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2  = 0.92, p myocardial salvage in experimental studies.

  11. Ramp Study Hemodynamics, Functional Capacity, and Outcome in Heart Failure Patients with Continuous-Flow Left Ventricular Assist Devices

    DEFF Research Database (Denmark)

    Jung, Mette H; Gustafsson, Finn; Houston, Brian

    2016-01-01

    Ramp studies-measuring changes in cardiac parameters as a function of serial pump speed changes (revolutions per minute [rpm])-are increasingly used to evaluate function and malfunction of continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that ramp studies can predict...... patients (HeartMate II, Thoratec Corporation, Pleasanton, CA). Functional status was evaluated in 70% (31/44); average 6 minute walk test (6MWT) was 312 ± 220 min, New York Heart Association (NYHA) I-II/III-IV (70/30%) and activity scores very low-low/moderate-very high (55/45%). Decrease in pulmonary...

  12. Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos.

    Science.gov (United States)

    Nahirney, Patrick C; Mikawa, Takashi; Fischman, Donald A

    2003-08-01

    During heart development, the proepicardium (PE) gives rise to cells of the epicardial epithelium, connective tissue of the subepicardium and the myocardium, and smooth muscle, endothelium, and connective tissue of the coronary arteries. The PE arises as an outgrowth of the pericardial serosa at embryonic day 2 (Hamburger and Hamilton stage [HH] 14) of chick development. Between stages HH14 and HH17, multicellular villous projections extend from the PE toward the dorsal aspect of the lesser curvature of the myocardium. On reaching the atrioventricular (AV) junction, the cells spread over the myocardium, eventually enveloping the complete heart surface as a simple squamous epithelium. Although the lineage of the PE cells is well established, it remains uncertain how cells of the PE reach the myocardial surface and specifically target the AV junction. By using a combination of serial section reconstructions, immunofluorescence, and electron microscopy, we have identified an extracellular matrix bridge (ECMB) spanning the coelomic cavity between the PE and the myocardium. The ECMB is first detectable at HH14 and persists until the PE contacts the bare myocardial surface. This ECMB stains intensely with ruthenium red and Alcian blue, contains heparan sulfate and fibronectin, and exhibits both fibrillar and globular ultrastructure, reminiscent of proteoglycans. After PE attachment to the myocardium (HH16-HH17), the subepicardium exhibited strong staining for heparan sulfate. Heparinase injection into the pericardial coelom at HH15 resulted in aberrant development of the primordial epicardium. On the basis of these studies, we suggest that the ECMB may participate in migration and targeting of the PE to the myocardium. Copyright 2003 Wiley-Liss, Inc.

  13. Análisis ecocardiográfico de la geometría ventricular izquierda en ratas espontáneamente hipertensas Echocardiographic study of left ventricular geometry the in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Eduardo M. Escudero

    2009-06-01

    Full Text Available El presente trabajo fue diseñado para analizar ecocardiográficamente la geometría del ventrículo izquierdo en ratas espontáneamente hipertensas (SHR. Se estudiaron 114 ratas macho de 4 meses de edad, 73 SHR y 41 Wistar (W a las que se les registró la presión arterial, la frecuencia cardíaca y se les realizó un ecocardiograma. Con las mediciones de diámetros y espesores de la pared ventricular izquierda se calcularon el espesor parietal relativo (h/r, el índice de masa del ventrículo izquierdo (IMVI, el volumen minuto, y el acortamiento medio ventricular. La geometría ventricular izquierda normal fue definida analizando el grupo de ratas normotensas y fijando los límites de IMVI y h/r a partir de la media más 2 desvíos estándar. Los patrones de geometría anormal se definieron como: remodelado concéntrico (RC: IMVI 0.71; hipertrofia excéntrica (HE: IMVI>2.06 mg/g - h/r 2.06 mg/g - h/r > 0.71. La presión arterial sistólica y el volumen minuto se utilizaron para estimar la resistencia periférica total (RPT. Doce por ciento de SHR presentaron geometría ventricular izquierda normal; 18% RC; 33% HC y 37% HE. El RC mostró el volumen latido más pequeño y la RPT más alta de cualquier grupo. HE presentó presión arterial sistólica similar a la de los otros grupos de SHR, volumen latido más alto y la RPT más baja. Estos hallazgos en SHR exhibiendo diferentes patrones de geometría ventricular izquierda, similares a los referidos en humanos, intensifican las similitudes entre la hipertensión esencial humana y las SHR.The purpose of this study was to analyze by echocardiogram left ventricular (LV geometry in spontaneously hypertensive rats (SHR. Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W. Left ventricular mass index (LVMI, relative wall thickness (RWT, stroke volume, and mid ventricular shortening were calculated with echocardiographic

  14. Tropical diseases of the myocardium: a review

    Directory of Open Access Journals (Sweden)

    Groom ZC

    2017-04-01

    Full Text Available Zoe C Groom,1 Aristotle D Protopapas,2 Vasileios Zochios3,4 1Costello Medical Consulting Limited, Cambridge, 2Department of Surgery, Division of Surgery and Cancer, Imperial College London, London, 3Department of Intensive Care Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, 4College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK Abstract: Cardiovascular diseases are widely distributed throughout the world. Human parasitic infections are ubiquitous. Tropical parasites are increasingly recognized as causes of cardiovascular diseases. In this review, we address the most frequently reported parasites that directly infect the myocardium, including Trypanosoma cruzi, the protozoal causative agent of American trypanosomiasis (Chagas disease, and Taenia solium, the cestode causative agent of taeniasis and cysticercosis. We also discuss tropical endomyocardial fibrosis, trichinellosis and schistosomiasis. Health systems, attitudes, the perceptions of both patients and physicians as well as socioeconomic factors should all be explored and recognized as crucial factors for improving the control of cardiovascular diseases in the tropics. Clinicians throughout the world must remain aware of imported parasites as potential causes of cardiac diseases. Keywords: cardiomyopathy, Chagas disease, myocardium, parasitic infection, tropical infections

  15. Alcohol consumption mitigates apoptosis and mammalian target of rapamycin signaling in myocardium.

    Science.gov (United States)

    Elmadhun, Nassrene Y; Sabe, Ashraf A; Lassaletta, Antonio D; Sellke, Frank W

    2014-06-01

    Epidemiologic studies have shown that individuals who consume low to moderate alcohol have a lower risk of cardiovascular disease developing compared with abstainers. Although experimental studies confirmed this observation, the effect of alcohol on ischemic myocardium is still unclear. We developed a clinically relevant animal model of chronic myocardial ischemia to investigate the effects of moderate alcohol consumption on the myocardium. Fourteen Yorkshire swine underwent placement of an ameroid constrictor to induce chronic myocardial ischemia. Postoperatively, one group was supplemented with 90 mL 50% EtOH daily (n = 7) and one group was supplemented with 80 g sucrose daily to normalize caloric intake between groups (n = 7). After 7 weeks, all animals underwent sternotomy, and harvest of the chronically ischemic myocardium and nonischemic myocardium. Tissues were analyzed for protein expression and stained for apoptosis quantification. In the ischemic myocardium, alcohol down-regulated the following proapoptotic proteins: tumor necrosis factor-α, forkhead box protein 03, BCL2-associated death promoter, and cysteine aspartic acid-specific protease 9; up-regulated the following prosurvival proteins: 5'adenosine monophosphate-activated protein kinase, phosphorylated 5'adenosine monophosphate-activated protein kinase, and phosphorylated forkhead box protein 03; and down-regulated mammalian target of rapamycin (MTOR) signaling by down-regulating MTOR, phosphorylated MTOR, and up-regulating Deptor. In the nonischemic myocardium, alcohol up-regulated prosurvival proteins: protein kinase B, phosphorylated protein kinase B, phosphorylated B-cell CLL/lymphoma 2, 5'adenosine monophosphate-activated protein kinase, phosphorylated BCL2-associated death promoter, phosphorylated forkhead box protein 03, and down-regulated MTOR signaling by down-regulating phosphorylated MTOR and up-regulating Deptor. Alcohol also decreased cell death as measured by terminal

  16. Engineered myocardium model to study the roles of HIF-1α and HIF1A-AS1 in paracrine-only signaling under pathological level oxidative stress.

    Science.gov (United States)

    Acun, Aylin; Zorlutuna, Pinar

    2017-08-01

    Studying heart tissue is critical for understanding and developing treatments for cardiovascular diseases. In this work, we fabricated precisely controlled and biomimetic engineered model tissues to study how cell-cell and cell-matrix interactions influence myocardial cell survival upon exposure to pathological level oxidative stress. Specifically, the interactions of endothelial cells (ECs) and cardiomyocytes (CMs), and the role of hypoxia inducible factor-1α (HIF-1α), with its novel alternative regulator, HIF-1α antisense RNA1 (HIF1A-AS1), in these interactions were investigated. We encapsulated CMs in photo-crosslinkable, biomimetic hydrogels with or without ECs, then exposed to oxidative stress followed by normoxia. With precisely controlled microenvironment provided by the model tissues, cell-cell interactions were restricted to be solely through the secreted factors. CM survival after oxidative stress was significantly improved, in the presence of ECs, when cells were in the model tissues that were functionalized with cell attachment motifs. Importantly, the cardioprotective effect of ECs was reduced when HIF-1α expression was knocked down suggesting that HIF-1α is involved in cardioprotection from oxidative damage, provided through secreted factors conferred by the ECs. Using model tissues, we showed that cell survival increased with increased cell-cell communication and enhanced cell-matrix interactions. In addition, whole genome transcriptome analysis showed, for the first time to our knowledge, a possible role for HIF1A-AS1 in oxidative regulation of HIF-1α. We showed that although HIF1A-AS1 knockdown helps CM survival, its effect is overridden by CM-EC bidirectional interactions as we showed that the conditioned media taken from the CM-EC co-cultures improved CM survival, regardless of HIF1A-AS1 expression. Cardiovascular diseases, most of which are associated with oxidative stress, is the most common cause of death worldwide. Thus, understanding

  17. Termination of ventricular tachycardia by far-field stimulation in humans: a feasibility study.

    Science.gov (United States)

    Lawo, Thomas; Schrader, Jürgen; Buddensiek, Michael; Schweika, Oliver; Mügge, Andreas; Bösche, Leif I

    2010-12-01

    Although a low-energy cardioversion (LEC) shock from an implantable cardioverter-defibrillator (ICD) can terminate ventricular tachycardia (VT), it frequently triggers ventricular fibrillation (VF) and is therefore not used in clinical practice. We tested whether a modified LEC shock with a very short duration (0.12-0.36 ms), termed "field stimulus," can terminate VT without triggering VF. In 13 sedated patients with implanted ICDs, we attempted to induce VT and to terminate the arrhythmias by field stimuli during hospital predischarge tests. In eight patients, 27 VT episodes were induced and treated with a total of 46 high-voltage (25-200 V) field stimuli, which terminated 11 VT episodes (41% efficacy) and never accelerated VT into VF. VT episodes slower than 230 beats per minute (bpm) (median rate) were terminated more successfully than faster arrhythmia episodes (69% vs 15%, P < 0.01). The strength of the field stimulus had no major influence on the effectiveness. We therefore postulate that suboptimal timing of field stimuli (delivered simultaneously with a sensed event in the right ventricular apex) was the main reason for failed VT terminations. A short (0.12-0.36 ms), high-voltage (50-100 V) field stimulus delivered from the shock coil of an implanted ICD system can safely terminate VT, especially for VT rates below 230 bpm. We believe that it would be reasonable to test the effectiveness of automatic field-stimulus therapy from implanted ICDs in VT episodes up to 230 bpm that are not susceptible to termination by antitachycardia pacing. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

  18. Ventricular defibrillation combining DC electrical field and electrical pacing: an optical mapping study

    Science.gov (United States)

    Musunuri, Sai Shruthi; Tang, Liang; Joung, Boyoung; Berbari, Edward J.; Lin, Shien-Fong

    2009-02-01

    Although high voltage direct current (DC) shock is a standard technique to terminate ventricular fibrillation (VF), it can cause severe pain and tissue damage. The exact effect of the DC electric field, which can depolarize the heart during VF is still unknown. We hypothesized that low-energy DC field in combination with pacing (pacing+DC) could terminate VF by affecting the ventricular propagation pattern. In six Langendorff-perfused isolated rabbit hearts with the ablated sinoatrial (SA) node, the DC field was delivered to the left ventricle (cathode) and right ventricle (anode). We designed a timed protocol using LabVIEW programming that delivers pacing, DC and pacing+DC stimuli for two seconds time intervals each. The pacing pulse (with varying pacing cycle length: 300ms-30ms) was delivered to the apex. Transmembrane voltage was recorded with optical mapping technique for 16 seconds at a sampling rate of 2ms/frame. We crushed the sinoatrial node to reduce the heart rate. The baseline activation appeared to have endocardial origins with a mean escape ventricular rate of 60 +/- 5bpm at baseline. The DC field (30mA-60mA) alone increased the mean heart rate to 120+/-5bpm. Although DC alone terminated VF in a few cases, the rate of termination was very low (6.2%). However, when pacing+DC was applied, it was possible to terminate VF in 34 of 130 episodes in six rabbits. The rate of successful defibrillation of VF with pacing+DC was significantly higher than that with DC alone (20% vs 6.2%, pdefibrillation with lower energy requirements.

  19. Non-excitatory electrical stimulation attenuates myocardial infarction via homeostasis of calcitonin gene-related peptide in myocardium.

    Science.gov (United States)

    Guo, Zhi-Jia; Guo, Zheng

    2015-03-01

    Electrical stimulation has been shown protection of brain, retina, optic nerves and pancreatic β-cells but the effect on cardio-protection is still unknown. Calcitonin gene-related peptide (CGRP) participates in the pathology of injury and protection of myocardium but whether or not electrical stimulation modulates endogenous CGRP is not clear. Male Sprague-Dawley rats were divided into 4 groups: (1) control group, without any treatment. (2) I/R group, animals were subjected to 30 min of myocardial ischemia followed by 60 min reperfusion. (3) NES+I/R group, non-excitatory electrical stimulation (NES) was commenced from 15 min before coronary artery occlusion till the end of reperfusion. (4) I/R+CGRP8-37 group, animals were given with CGRP8-37 (an antagonist of CGRP receptor, 10(-7) mol/L, 0.3 ml, i.v.) at 5 min before reperfusion without any electrical stimulation. The hemodynamics and electrocardiogram were monitored and recorded. Infarct size and troponin I were examined and CGRP expression in the myocardium and serum was analyzed. It was found that the infarct size and TnI were significantly reduced in NES+I/R group, by 45% and 58% respectively, accompanied by an obvious fall back of CGRP in myocardium, compared to I/R group (all pTreatment with CGRP8-37 resulted in the same protection on myocardium as NES did. No significant difference in hemodynamics or ventricular tachycardia was detected among the groups (all p>0.05). It can be concluded that NES reduced the infarction size after acute myocardial ischemia and reperfusion, for which the underlying mechanism may be associated with modulation of endogenous CGRP in myocardium. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study.

    Science.gov (United States)

    Cairns, J A; Connolly, S J; Gent, M; Roberts, R

    1991-08-01

    Among survivors of acute myocardial infarction, frequent and repetitive ventricular premature depolarizations (VPDs) detected on ambulatory monitoring contribute independently to the risk of all-cause mortality and sudden death. Apart from the beta-blockers, no antiarrhythmic drug has been reliably demonstrated to reduce mortality among patients with VPDs. A pilot study was undertaken to gather data to aid in the design of a multicenter trial of amiodarone for the reduction of mortality from cardiac arrhythmias in such patients. Seventy-seven patients with acute myocardial infarction within the previous 6-30 days and 10 or more VPDs/hr or one or more runs of ventricular tachycardia on 24-hour electrocardiographic recording were randomized in a double-blind fashion in a 2:1 amiodarone-to-placebo ratio. The loading dose was 10 mg/kg/day for 3 weeks. The maintenance dose was 300-400 mg/day with reductions at 4-month intervals in response to VPD suppression, excessive plasma levels, or toxicity. VPD suppression at 1 week and 2 weeks was 63% and 85%, respectively, on amiodarone and 17% and 27%, respectively, on placebo. Apart from thyroid-stimulating hormone elevation and skin reactions, no side effects occurred more frequently with amiodarone. The study drug was stopped for side effects or noncompliance in 35% of amiodarone patients and 34% of placebo patients. Patients were followed for a maximum of 2 years (mean, 20 months). Arrhythmic death or resuscitated ventricular fibrillation occurred in two of 48 amiodarone patients (6%) and four of 29 placebo patients (14%), whereas the rates of all-cause mortality were five of 48 (10%) and six of 29 (21%), respectively. Amiodarone, in moderate loading and maintenance dosages with adjustments in response to plasma levels, VPD suppression, and side effects, results in effective VPD suppression and acceptable levels of toxicity.

  1. Arrhythmogenic right ventricular cardiomyopathy/dysplasia

    Directory of Open Access Journals (Sweden)

    Basso Cristina

    2007-11-01

    Full Text Available Abstract Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs

  2. Salvianolic acid b alleviating myocardium injury in ischemia ...

    African Journals Online (AJOL)

    Salvianolic acid b alleviating myocardium injury in ischemia reperfusion rats. ... increased contents of myocardium antioxidant enzymes activities; western blot results showed that Sal B ameliorate the increased Bax and caspase-3 protins expressions and decreased Bcl-2 proteins expression and ratios of Bcl-2 to Bax.

  3. Quantification of left ventricular myocardial collagen system in children, young adults, and the elderly

    Directory of Open Access Journals (Sweden)

    Andrea Bogoslavsky Levy Mendes

    2012-06-01

    Full Text Available Studies on the collagen system of the human myocardium are still limited compared to those on small laboratory animals. The aim of this work was to observe the collagen tissue of the myocardium of the human heart as a function of age. The types of collagen, as well as the density of collagen tissue and the diameter of collagen fibrils, were examined. Fragments of the left ventricular wall from 15 hearts, 5 from children, 5 from young adults, and 5 from elderly individuals, were analyzed by using the Picrosirius-polarization method and by transmission electron microscopy (TEM. The results showed the presence of collagen type III and collagen type I, both in the endomysium and perimysium of the 3 groups studied. Measurements of collagen content in myocardial tissue displayed that both endomysial and perimysial collagen increase in number and thickness in the adult and elderly. These histochemical results coincided with the observations obtained with the electron microscope in showing an increase in the number of collagen fibrils with a large diameter in the adult and elderly hearts. The present results on cardiac collagen may be important for assessing the pathogenesis of several cardiopathies in the hearts of children, young adults, and the elderly.

  4. Stunned myocardium after an anesthetic procedure in a pediatric patient - case report.

    Science.gov (United States)

    Faleiro Oliveira, Joana; Rebelo Pacheco, Susana; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Rebelo, Mónica; Loureiro, Helena; Almeida, Helena

    2016-06-01

    Takotsubo syndrome (TTS) is an acquired transient type of systolic dysfunction which mimics myocardial infarction clinically and electrocardiographically. TTS is also known as stress cardiomyopathy, broken heart syndrome, apical ballooning, reversible acute heart failure, neurogenic stunned myocardium or acute catecholamine cardiomyopathy. This case report describes an uncommon presentation of myocardial stunning after an anesthetic procedure. A 14-year-old girl with a history of pineal cyst and hemiplegic migraine was admitted for control brain magnetic resonance imaging. During anesthesia induction with propofol she suffered bradycardia, which was reversed with atropine, followed by tachyarrhythmia, reversed with lidocaine and precordial thump. Within hours she developed pulmonary edema and global respiratory failure due to acute left ventricular dysfunction. A transthoracic echocardiogram showed a dilated left ventricle with global hypokinesia and depressed left ventricular systolic function (ejection fraction digoxin and dopamine. The clinical course was satisfactory with clinical, biochemical and echocardiographic improvement within four days. Subsequent echocardiograms showed no ventricular dysfunction. The patient was discharged home on carvedilol, which was discontinued after normalization of cardiac function on cardiac magnetic resonance imaging. Few cases of TTS have been described in children, some of them triggered by acute central nervous system disorders and others not fulfilling all the classical diagnostic criteria. In this case the anesthetic procedure probably triggered the TTS. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.

    Science.gov (United States)

    Yang, Jia-Ying; Deng, Wu; Chen, Yumay; Fan, Weiwei; Baldwin, Kenneth M; Jope, Richard S; Wallace, Douglas C; Wang, Ping H

    2013-06-01

    Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Left Ventricular Myocardial Deformation Parameters Are Affected by Coronary Slow Flow Phenomenon: A Study of Speckle Tracking Echocardiography.

    Science.gov (United States)

    Gulel, Okan; Akcay, Murat; Soylu, Korhan; Aksan, Gokhan; Yuksel, Serkan; Zengin, Halit; Meric, Murat; Sahin, Mahmut

    2016-05-01

    The coronary slow flow phenomenon (CSFP) is defined as a delayed distal vessel contrast opacification in the absence of obstructive epicardial coronary artery disease during coronary angiography. There is conflicting data in medical literature regarding the effects of CSFP on the left ventricular functions assessed by conventional echocardiography or tissue Doppler imaging. Therefore, we aimed to evaluate whether there is any abnormality in the myocardial deformation parameters (strain, strain rate (SR), rotation, twist) of the left ventricle obtained by speckle tracking echocardiography (STE) in patients with CSFP. Twenty patients with CSFP were included prospectively in the study. Another 20 patients with similar demographics and cardiovascular risk factors as well as normal coronary angiography were used as the control group. Two-dimensional echocardiographic images of the left ventricle from the apical long-axis, two-chamber, four-chamber, and parasternal short-axis views were used for STE analysis. The analysis of left ventricular circumferential deformation parameters showed that the averaged peak systolic strain, systolic SR, and early diastolic SR values were significantly lower in patients with CSFP (P = 0.009, P = 0.02, and P = 0.02, respectively). Among the left ventricular rotation and twist values, apical rotation was significantly lower in patients with CSFP (P = 0.02). Further, the mean thrombolysis in myocardial infarction frame count value was found to be negatively correlated with the averaged peak circumferential early diastolic SR (r = -0.35, P = 0.03). It was positively correlated with the averaged peak circumferential systolic strain (r = 0.47, P = 0.003) and circumferential systolic SR (r = 0.46, P = 0.005). Coronary slow flow phenomenon leads to significant alterations in the myocardial deformation parameters of the left ventricle as assessed by STE. Specifically, circumferential deformation parameters are affected in CSFP patients. © 2015

  7. Infective endocarditis following patch closure of ventricular septal defect: a cross-sectional Doppler echocardiographic study.

    Science.gov (United States)

    Shrivastava, S; Radhakrishnan, S

    1989-10-01

    Cross-sectional and Doppler echocardiographic characteristics of infective endocarditis are described in six cases following patch closure of a ventricular septal defect. The patients presented to us with fever one to five months after surgery. Five of them also had congestive cardiac failure. Cross-sectional echocardiography showed large masses over the patch in all cases. Dehiscence of the lower end of the patch was identified in three of them, and, in two cases, the right sinus of Valsalva had ruptured into the right ventricle. Doppler detected turbulent flow in the right ventricle in five cases, and a continuous signal indicating an aorto-right ventricular communication in two cases. A signal indicative of aortic regurgitation was also found in the latter two cases. Staphylococcus aureus was cultured from the blood in three cases and Aspergillus was identified at autopsy in one. The echocardiographic findings were confirmed in three cases (one during surgery and two at autopsy). Dehiscence of the patch and large masses were associated with a poor prognosis.

  8. Incidence of ventricular arrhythmias, brady-arrhythmias and sudden ...

    African Journals Online (AJOL)

    Ventricular arrhythmias (VAS), Including ventricular tachycardia (VT), ventricular fibrillation (VF) and Brady-arrhythmias, are life-threatening complications of acute myocardial infarction (MI). Objective: To study the incidence of ventricular arrhythmias, brady-arrhythmias and Sudden Cardiac Death (SCD) in Sudanese ...

  9. Association of left ventricular dilatation and hypertrophy with chronotropic incompetence in the Framingham Heart Study.

    Science.gov (United States)

    Lauer, M S; Larson, M G; Evans, J C; Levy, D

    1999-05-01

    Chronotropic incompetence and left ventricular (LV) dilatation have both been shown to be markers of an adverse cardiovascular prognosis. Chronotropic incompetence has been described in patients with symptomatic LV dilatation and dysfunction, but the effect of asymptomatic LV dilatation and hypertrophy on exercise heart rate response has not been well characterized. Members of the Framingham Offspring Study underwent M-mode echocardiography and graded exercise testing as part of a routine evaluation. Subjects receiving beta-blockers and digitalis and subjects with preexisting coronary heart disease, heart failure, and baseline ST-segment abnormalities were excluded. Chronotropic incompetence was assessed in 2 ways: (1) failure to achieve an age--predicted target heart rate and (2) a low chronotropic index, a measure of heart rate response that takes into account effects of age, resting heart rate, and physical fitness. Echocardiographic variables studied included LV diastolic and systolic dimensions, LV wall thickness, LV mass, and fractional shortening. There were 1414 men and 1601 women eligible for analyses; failure to reach target heart rate occurred in 20% of men and 23% of women; a low chronotropic index was noted in 14% of men and 12% of women. In unadjusted categorical analyses, an abnormally high LV mass, as defined by exceeding the 90th percentile predicted value of a healthy reference group, was associated with failure to achieve target heart rate in men (31% vs 18%, odds ratio [OR] 2.05, 95% confidence interval [CI] 1.49 to 2.83) and women (34% vs 20%, OR 2.09, 95% CI 1.63 to 2.69). Similarly, an abnormally high LV mass was predictive of a low chronotropic index in men (18% vs 13%, OR 1. 47, 95% CI 1.01 to 2.14) and women (17% vs 10%, OR 1.78, 95% CI 1.29 to 2.45). When considered as a continuous variable, LV diastolic dimension predicted failure to achieve target heart rate in men (ageadjusted OR for 1 SD increase 1.30, 95% CI 1.00 to 1.33) and in

  10. Detection and characterization of left Ventricular Thrombi by MRT compared to Transthoracic Echocardiography; Detektion und Charakterisierung linksventrikulaerer Thromben mittels MRT im Vergleich zur transthorakalen Echokardiographie

    Energy Technology Data Exchange (ETDEWEB)

    Bruder, O.; Jochims, M.; Sabin, G.V. [Klinik fuer Kardiologie und Angiologie, Elisabeth - Krankenhaus Essen (Germany); Waltering, K.U.; Hunhold, P.; Narin, B.; Barkhausen, J. [Institut fuer Diagnostische und Interventionelle Radiologie, Universitaetsklinikum Essen (Germany)

    2005-03-01

    Purpose: Transthoracic echocardiography is the routine diagnostic procedure in assessing patients with left ventricular thrombi, but is limited by the acoustic window and poor contrast between thrombus and adjacent myocardium. This study evaluates the role of cardiac MRI in the detection of left ventricular thrombi in patients with chronic myocardial infarction compared to standard transthoracic echocardiography. Materials and Methods: In 82 patients (55 men and 27 women, age 36 to 79 years, median 59{+-}11 years) who suffered a myocardial infarction more than 6 months earlier, transthoracic echocardiography and MRI were performed. The MRI protocol included steady state cine imaging (true FISP: TR 3.0 ms, TE 1.5 ms, FA 65 ) in standard long and short axis orientation and contrast-enhanced imaging using a 3D IR-FLASH sequence with long inversion time (TR 4 ms; TE 1.43 ms, FA 10 , TI 300 ms) early, and a 2D IR-FLASH sequence with optimized inversion time (TR 8 ms, TE 4.3 ms, FA 20 , TI 180-280 ms) late after administration of gadolinium. Results: Transthoracic echocardiography depicted 12 thrombi. Contrast-enhanced MRI confirmed these 12 thrombi and detected 23 additional thrombi. With the exception of 2 very small apical thrombi only visible on contrast-enhanced MRI images, spherical thrombi were diagnosed by both techiques, whereas only contrast-enhanced MRI was able to visualize mural thrombi. Left ventricular thrombi were more frequently diagnosed in patients with moderate to severe impairment of the left ventricular systolic function, 32/42 (76%), or in patients with left ventricular aneurysms, 21/24 (84%). Conclusion: Contrast-enhanced MRI is mostly superior to transthoracic echocardiography in diagnosing mural left ventricular thrombi in patients who had suffered a myocardial infarction. Intracavitray thrombi are mor frequently found in patients with impaired regional and global left ventricular function. (orig.)

  11. Arrhythmogenic right ventricular cardiomyopathy: contribution of different electrocardiographic techniques.

    Science.gov (United States)

    Moreira, Davide; Delgado, Anne; Marmelo, Bruno; Correia, Emanuel; Gama, Pedro; Pipa, João; Nunes, Luís; Santos, Oliveira

    2014-04-01

    Arrhythmogenic right ventricular cardiomyopathy, also known as arrhythmogenic right ventricular dysplasia, is a condition in which myocardium is replaced by fibrous or fibrofatty tissue, predominantly in the right ventricle. It is clinically characterized by potentially lethal ventricular arrhythmias, and is a leading cause of sudden cardiac death. Its prevalence is not known exactly but is estimated at approximately 1:5000 in the adult population. Diagnosis can be on the basis of structural and functional alterations of the right ventricle, electrocardiographic abnormalities (including depolarization and repolarization alterations and ventricular arrhythmias) and family history. Diagnostic criteria facilitate the recognition and interpretation of non-specific clinical features of this disease. The authors present a case in which the diagnosis of arrhythmogenic right ventricular cardiomyopathy was prompted by the suspicion of right ventricular disease on transthoracic echocardiography. This was confirmed by detection of epsilon waves on analysis of the ECG, which generally go unnoticed but in this case were the key to the diagnosis. Their presence was also shown by non-conventional ECG techniques such as modified Fontaine ECG. The course of the disease culminated in the occurrence of ventricular tachycardia, which prompted placement of an implantable cardioverter-defibrillator. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  12. Modeling envelope statistics of blood and myocardium for segmentation of echocardiographic images.

    NARCIS (Netherlands)

    Nillesen, M.M.; Lopata, R.G.P.; Gerrits, I.H.; Kapusta, L.; Thijssen, J.M.; Korte, C.L. de

    2008-01-01

    The objective of this study was to investigate the use of speckle statistics as a preprocessing step for segmentation of the myocardium in echocardiographic images. Three-dimensional (3D) and biplane image sequences of the left ventricle of two healthy children and one dog (beagle) were acquired.

  13. Development of the myocardium of the atrioventricular canal and the vestibular spine in the human heart

    NARCIS (Netherlands)

    Kim, J. S.; Virágh, S.; Moorman, A. F.; Anderson, R. H.; Lamers, W. H.

    2001-01-01

    To establish the morphogenetic mechanisms underlying formation and separation of the atrioventricular connections, we studied the remodeling of the myocardium of the atrioventricular canal and the extracardiac mesenchymal tissue of the vestibular spine in human embryonic hearts from 4.5 to 10 weeks

  14. Relaxation and the Role of Calcium in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction.

    Science.gov (United States)

    Runte, K Elisabeth; Bell, Stephen P; Selby, Donald E; Häußler, Tim N; Ashikaga, Takamuru; LeWinter, Martin M; Palmer, Bradley M; Meyer, Markus

    2017-08-01

    Relaxation characteristics and Ca(2+) homeostasis have not been studied in isolated myocardium from patients with hypertensive heart disease (HHD) and heart failure with preserved ejection fraction (HFpEF). Prolonged myocardial relaxation is believed to play an important role in the pathophysiology of these conditions. In this study, we evaluated relaxation parameters, myocardial calcium (Ca(2+)), and sodium (Na(+)) handling, as well as ion transporter expression and tested the effect of Na(+)-influx inhibitors on relaxation in isolated myocardium from patients with HHD and HFpEF. Relaxation characteristics were studied in myocardial strip preparations under physiological conditions at stimulation rates of 60 and 180 per minute. Intracellular Ca(2+) and Na(+) were simultaneously assessed using Fura-2 and AsanteNATRIUMGreen-2, whereas elemental analysis was used to measure total myocardial concentrations of Ca, Na, and other elements. Quantitative polymerase chain reaction was used to measure expression levels of key ion transport proteins. The lusitropic effect of Na(+)-influx inhibitors ranolazine, furosemide, and amiloride was evaluated. Myocardial left ventricular biopsies were obtained from 36 control patients, 29 HHD and 19 HHD+HFpEF. When compared with control patients, half maximal relaxation time (RT50) at 60 per minute was prolonged by 13% in HHD and by 18% in HHD+HFpEF (both Pmyocardium from patients with HHD and HHD+HFpEF. This leads to incomplete relaxation at higher rates. Elevated calcium levels in HFpEF are neither a result of an impaired Na(+) gradient nor expression changes in key ion transporters and regulatory proteins. © 2017 American Heart Association, Inc.

  15. Deteriorating glucose tolerance status is associated with left ventricular dysfunction--the Hoorn Study.

    Science.gov (United States)

    Henry, R M A; Paulus, W J; Kamp, O; Kostense, P J; Spijkerman, A M W; Dekker, J M; Nijpels, G; Heine, R J; Bouter, L M; Stehouwer, C D A

    2008-03-01

    Type 2 diabetes (DM2) is associated with a greater risk of heart failure. The mechanisms underlying this association remain controversial and include diabetes-associated hypertension and obesity, impaired small and large artery function, and a distinct metabolic cardiomyopathy related to hyperglycaemia/ hyperinsulinaemia. The proximate causes of heart failure are left ventricular (LV) systolic dysfunction (SDF) and diastolic dysfunction (DDF). We investigated, in a population-based cohort (n=746), the association between glucose tolerance status and SDF and DDF . The study population consisted of 274 individuals with normal glucose metabolism (NGM), 174 with impaired glucose metabolism (IGM) and 298 with DM2 (mean age 68.5 years). All participants underwent an LV echocardiogram. SDF was defined as ejection fraction DDF was determined by a sum score of peak A velocity (abnormal, >or =97 cm/s), the difference between Apv and Amv duration (> or =41 ms), and left atrial volume (> or =57 ml), where cut-off values were based upon the 90th percentile in NGM. In addition, we analysed the ratio of early to late diastolic filling (E/A ratio) on a continuous scale using linear regression analyses. The age- and sex-standardised prevalences in NGM, IGM and DM2 were 13, 14 and 30% for SDF , and 26, 36 and 47% for DDF (P trend for both DDF (2.42 (1.63 to 3.60)) (90th percentile definition). This was also true for the analyses with the E/A ratio on a continuous scale (regression coefficient b (95% CI) -0.05 (-0.09 to -0.01). After adjustment for sex, age, hypertension, body mass index, prior cardiovascular disease and (micro) albuminuria IGM was not significantly associated with SDF (odds ratio (95% CI) 1.04 (0.58 to 1.88)) or DDF (1.33 (0.86 to 2.06)) using the definition based upon the 90th percentile. However, IGM was significantly associated with DDF if the E/A ratio was analysed on a continuous scale (regression coefficient beta (95% CI) -0.05 (-0.10 to -0.01). Additional

  16. [Late potentials and ventricular arrhythmia].

    Science.gov (United States)

    Adamec, R; Zimmermann, M

    1986-04-01

    When electrodes are placed at the surface of the thorax, high-amplification electrocardiography (HA-ECG) combined with signal summation as a function of time provides a non-invasive method for detecting electric potentials occurring after the QRS complex of the clinical electrocardiogram. These potentials are called late, and can probably be likened to the "divided" or "fragmented" potentials recorded directly on the heart or in its ventricles near zones of ischemia, infarction or aneurysm. The prevalence of late potentials of ventricular activation (LPVA) and their association with the occurrence of ventricular arrhythmias seems well established, notably in the presence of ventricular aneurysm and anamnesis of severe ventricular arrhythmia. Some studies have shown that detection of LPVAs is of value in identifying heart patients at risk of ventricular arrhythmia or sudden death. Heart disease aside, the presence of LPVAs has been demonstrated in arrhythmogenic right ventricular dysplasia and reported in Fallot's tetralogy after complete correction. A standardization of recordings and a more precise definition of LPVAs are necessary before HA-ECG can become a routine clinical method. Further, the possibility of "beat by beat" recordings with "spatial" summation will allow detection of LPVAs which vary with time and in nature and hence provide a better understanding of the genesis of ventricular arrhythmias.

  17. Predictors of left ventricular remodeling after ST-elevation myocardial infarction.

    Science.gov (United States)

    Hendriks, Tom; Hartman, Minke H T; Vlaar, Pieter J J; Prakken, Niek H J; van der Ende, Yldau M Y; Lexis, Chris P H; van Veldhuisen, Dirk J; van der Horst, Iwan C C; Lipsic, Erik; Nijveldt, Robin; van der Harst, Pim

    2017-09-01

    Adverse left ventricular (LV) remodeling after acute ST-elevation myocardial infarction (STEMI) is associated with morbidity and mortality. We studied clinical, biochemical and angiographic determinants of LV end diastolic volume index (LVEDVi), end systolic volume index (LVESVi) and mass index (LVMi) as global LV remodeling parameters 4 months after STEMI, as well as end diastolic wall thickness (EDWT) and end systolic wall thickness (ESWT) of the non-infarcted myocardium, as compensatory remote LV remodeling parameters. Data was collected in 271 patients participating in the GIPS-III trial, presenting with a first STEMI. Laboratory measures were collected at baseline, 2 weeks, and 6-8 weeks. Cardiovascular magnetic resonance imaging (CMR) was performed 4 months after STEMI. Linear regression analyses were performed to determine predictors. At baseline, patients were 21% female, median age was 58 years. At 4 months, mean LV ejection fraction (LVEF) was 54 ± 9%, mean infarct size was 9.0 ± 7.9% of LVM. Strongest univariate predictors (all p infarcted myocardium.

  18. Application of the moving-actuator type pump as a ventricular assist device: in vitro and in vivo studies.

    Science.gov (United States)

    Lee, H S; Rho, Y R; Park, C Y; Hwang, C M; Kim, W G; Sun, K; Choi, M J; Lee, K K; Cheong, J T; Shim, E B; Min, B G

    2002-06-01

    A moving actuator type pump has been developed as a multifunctional Korean artificial heart (AnyHeart). The pump consists of a moving actuator as an energy converter, right and left sacs, polymer (or mechanical) valves, and a rigid polyurethane housing. The actuator containing a brushless DC motor moves back and forth on an epicyclical gear train to produce a pendular motion, which compresses both sacs alternately. Of its versatile functions of ventricular assist device and total artificial heart use, we have evaluated the system performance as a single or biventricular assist device through in vitro and in vivo experiments. Pump performance and anatomical feasibility were tested using various animals of different sizes. In the case of single ventricular assist device (VAD) use, one of the sacs remained empty and a mini-compliance chamber was attached to either an outflow or inflow port of the unused sac. The in vitro and in vivo studies show acceptable performance and pump behavior. Further extensive study is required to proceed to human application.

  19. Incidence and clinical relevance of slow ventricular tachycardia in implantable cardioverter-defibrillator recipients: an international multicenter prospective study.

    Science.gov (United States)

    Sadoul, Nicolas; Mletzko, Ralph; Anselme, Frédéric; Bowes, Robert; Schöls, Wolfgang; Kouakam, Claude; Casteigneau, Gaëlle; Luise, Raffaele; Iscolo, Nicolas; Aliot, Etienne

    2005-08-16

    This study aims to assess the incidence and clinical relevance of slow ventricular tachycardia (VT) and the effectiveness and/or deleterious effects of antitachycardia pacing in slow VT in implantable cardioverter-defibrillator recipients. This multicenter prospective randomized study included 374 patients (326 men) without prior history of slow VT (148 bpm), and a ventricular fibrillation zone. Patients were randomized to a treatment group (n=183) with therapy activated in the slow VT zone or a monitoring group (n=191) with no therapy in the slow VT zone. During follow-up (11 months), 449 slow VTs occurred in 114 patients (30.5% slow VT incidence); 181 VTs (54 patients) occurred in the monitoring group; 3 were readmitted to the hospital; and lightheadedness and palpitations occurred in 4 and 250 (60 patients) in the treatment group treated by antitachycardia pacing (89.8% success rate) and shock delivery (n=2). There were 10 crossovers from the monitoring to treatment group and 3 crossovers from the treatment to monitoring group (P=0.09). Quality of life scores were not different between groups. Slow VT incidence (<150 bpm) is high (30%) in implantable cardioverter-defibrillator recipients without prior history of slow VT, has limited clinical relevance, and is efficiently and safely terminated by antitachycardia pacing.

  20. The management of ventricular dysrhythmia in aconite poisoning.

    Science.gov (United States)

    Coulson, James M; Caparrotta, Thomas M; Thompson, John P

    2017-06-01

    Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to the presence of an admixture of alkaloids present in all parts of the plant. The major target of these aconite alkaloids is the fast voltage-gates sodium channel, where they cause persistent activation. This blockade of the channel in the activated state promotes automaticity within the ventricular myocardium and the generation of ventricular arrhythmias. Aconitine-induced arrhythmias: Aconite alkaloids are known to cause many different types of disturbance of heart rhythm. However, this focused review specifically looks at ventricular rhythm disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des pointes and ventricular fibrillation. The objective of this review was to identify the outcome of anti-dysrhythmic strategies from animal studies and case reports in humans in order to guide the management of ventricular dysrhythmias in aconite poisoning in humans. A review of the literature in English was conducted in PubMed and Google Scholar from 1966 to July 2016 using the search terms "aconite/aconitine"; "aconite/aconitine + poisoning" and "aconite/aconitine + dysrhythmia". 168 human case-reports and case-series were identified by these searches, of which 103 were rejected if exposure to aconite did not result in ventricular dysrhythmias, if it was uncertain as to whether aconite had been ingested, if other agents were co-ingested, if there was insufficient information to determine the type of treatments administered or if there was insufficient information to determine outcome. Thus, 65 case reports of probable aconite poisoning that resulted in ventricular dysrhythmias were identified. Toxicokinetic data in aconite poisoning: Data were only available in three papers; the presence of ventricular rhythm disturbances

  1. Fatal arrhythmogenic right ventricular cardiomyopathy in 2 related subadult chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Tong, L J; Flach, E J; Sheppard, M N; Pocknell, A; Banerjee, A A; Boswood, A; Bouts, T; Routh, A; Feltrer, Y

    2014-07-01

    Cardiovascular disease is increasingly recognized as an important cause of morbidity and mortality in captive chimpanzees (Pan troglodytes). This report records 2 cases of sudden cardiac death in closely related subadult captive chimpanzees with marked replacement fibrosis and adipocyte infiltration of the myocardium, which resemble specific atypical forms of the familial human disease arrhythmogenic right ventricular cardiomyopathy. Changes were consistent with left-dominant and biventricular subtypes, which are both phenotypic variants found within human families with familial arrhythmogenic right ventricular cardiomyopathy. Previously reported fibrosing cardiomyopathies in chimpanzees were characterized by nonspecific interstitial fibrosis, in contrast to the replacement fibrofatty infiltration with predilection for the outer myocardium seen in these 2 cases. To the authors' knowledge, this case report is the first to describe cardiomyopathy resembling arrhythmogenic right ventricular cardiomyopathy in nonhuman primates and the first to describe left-dominant arrhythmogenic cardiomyopathy-type lesions in an animal. © The Author(s) 2013.

  2. Hemodynamic effects of ventricular defibrillation

    Science.gov (United States)

    Pansegrau, Donald G.; Abboud, François M.

    1970-01-01

    Hemodynamic responses to ventricular defibrillation were studied in anesthetized dogs. Observations were made on arterial, right atrial and left ventricular end-diastolic pressures, on cardiac output (dye dilution), heart rate, and right atrial electrocardiogram. Ventricular fibrillation was induced electrically with a bipolar electrode catheter placed in the right ventricle. Fibrillation was maintained for 15 or 30 sec and terminated with a 400 w sec capacitor discharge across the thoracic cage. Responses lasted 1-10 min after conversion and included a cholinergic and an adrenergic component. The cholinergic component was characterized by sinus bradycardia, periods of sinus arrest, atrioventricular block, and ventricular premature beats. The adrenergic component included increases in arterial pressure, in cardiac output, and in left ventricular stroke work at a time when left ventricular end-diastolic pressure was normal; there was no change in total peripheral resistance. The pH of arterial blood decreased slightly and pCO2 increased but pO2 and the concentration of lactate were unchanged. Bilateral vagotomy and intravenous administration of atropine blocked the cholinergic component, unmasked a sinus tachycardia, and accentuated the adrenergic component of the response. The latter was blocked by intravenous administration of propranolol and phenoxybenzamine. These responses were related primarily to conversion of ventricular fibrillation rather than to the electrical discharge of countershock because countershock without ventricular fibrillation caused more transient and smaller responses than those observed with defibrillation: furthermore, the hemodynamic effects of defibrillation were augmented by prolongation of the duration of fibrillation. The results suggest that the cholinergic component of the response may be detrimental in that it favors spontaneous recurrence of fibrillation; on the other hand, the adrenergic component may be essential for conversion

  3. Slackness between vessel and myocardium is necessary for coronary flow reserve

    Science.gov (United States)

    Young, Jonathan M.; Choy, Jenny S.; Kassab, Ghassan S.

    2012-01-01

    Tone regulation in coronary microvessels has largely been studied in isolated vessels in the absence of myocardial tethering. Here, the potential effect of radial tethering and interstitial space connective tissue (ISCT) between coronary microvessels and the surrounding myocardium was studied. We hypothesized that rigid tethering between microvessels and the myocardium would constrain the active contraction of arterioles and is not compatible with the observed tone regulation. The ISCT between coronary microvessels and myocardium in five swine was found to increase exponentially from 0.22 ± 0.02 μm in capillaries (modified Strahler order 0) of the endocardium to 34.9 ± 7.1 μm in epicardial vessels (order 10). Microvessels with both soft tethering and ISCT gap were capable of significant changes in vessel resistance (up to an ∼1,600% increase), consistent with experimental measurements of high coronary flow reserve. Additionally, the mechanical energy required for myogenic contraction was estimated. The results indicate that rigid tethering requires up to four times more mechanical energy than soft tethering in the absence of a gap. Hence, the experimental measurements and model predictions suggest that effectiveness and efficiency in tone regulation can be achieved only if the vessel is both softly tethered to and separated from the myocardium in accordance with the experimental findings of ISCT gap. These results have fundamental implications on future simulations of coronary circulation. PMID:22408024

  4. Superior performance of continuous over pulsatile flow ventricular assist devices in the single ventricle circulation: A computational study.

    Science.gov (United States)

    Schmidt, Tyler; Rosenthal, David; Reinhartz, Olaf; Riemer, Kirk; He, Fei; Hsia, Tain-Yen; Marsden, Alison; Kung, Ethan

    2017-02-08

    This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30m(2)) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous flow VAD CO was at least 0.99L/min greater than the optimized pulsatile flow VAD CO (p=0.001). The 25 and 50mL pulsatile flow VADs exhibited incomplete filling at higher heart rates that reduced CO as much as 9.7% and 37.3% below expectations respectively. Optimization of pulsatile flow VAD settings did not achieve statistically significant (p<0.05) improvement to CO. Results corroborate clinical experience that continuous flow VADs produce higher CO and superior ventricular unloading in single ventricle patients. Impaired filling leads to performance degradation of pulsatile flow VADs in the single ventricle circulation. Published by Elsevier Ltd.

  5. Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic inhomogeneity of sympathetic innervation in the absence of infarction.

    Science.gov (United States)

    Luisi, Andrew J; Suzuki, Gen; Dekemp, Robert; Haka, Michael S; Toorongian, Steven A; Canty, John M; Fallavollita, James A

    2005-08-01

    We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium. Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately. After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after

  6. Stochastic pacing effect on cardiac alternans--simulation study of a 2D human ventricular tissue.

    Science.gov (United States)

    Dvir, Hila; Zlochiver, Sharon

    2013-01-01

    The physiological heart rate is not deterministic but rather varies in time; those variations are termed heart rate variability (HRV). It is well known that low HRV is often seen in patients prone to arrhythmias. The ability of HRV to predict arrhythmia events is traditionally attributed to an impaired balance between the autonomic sympathetic and parasympathetic tone. However, there is no concrete model that directly relates low HRV to the electrical conduction in the cardiac tissue and to arrhythmogenic dynamic properties. We simulated stochastic cardiac pacing with Gaussian distribution using 2D human ventricular tissue model. Conduction stabilization was obtained with stochastic pacing owing to reduced propensity of the appearance of action potential duration (APD) discordant alternans and reduced APD spatial heterogeneity.

  7. Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling: a functional and molecular study.

    Science.gov (United States)

    Beeri, Ronen; Yosefy, Chaim; Guerrero, J Luis; Abedat, Suzan; Handschumacher, Mark D; Stroud, Robert E; Sullivan, Suzanne; Chaput, Miguel; Gilon, Dan; Vlahakes, Gus J; Spinale, Francis G; Hajjar, Roger J; Levine, Robert A

    2007-09-11

    Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling. Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically. Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.

  8. Functional and ultrastructural alterations of canine myocardium subjected to very brief coronary occlusions.

    Science.gov (United States)

    Pomar, F; Cosin, J; Portoles, M; Faura, M; Renau-Piqueras, J; Hernandiz, A; Andres, F; Colomer, J L; Graullera, B

    1995-11-01

    The effects of very brief and recurrent coronary occlusions on myocardial regional shortening and its ultrastructure have been analysed. Ultrasonic crystals were implanted in the left ventricular subendocardium of 23 anaesthetized dogs with the thorax open, to measure the shortening fractions of an ischaemic and a control segment. Twenty 2 min total occlusions were provoked in the left anterior descending coronary artery, with 3 min recovery intervals (reperfusion) between occlusions. The shortening fraction decreased progressively with each occlusion, reaching a value 18.9% lower than the basal after the last ischaemic episode (P myocardium is subjected to very brief and repeated coronary occlusions, there is progressive deterioration of systolic function with structural alterations, mainly at the mitochondrial level. These modifications are still observable 24 h after the end of ischaemic stimulation and could be the cause of transitory and/or chronic systolic dysfunctions in the absence of previous heart attack.

  9. Residual Stress Impairs Pump Function After Surgical Ventricular Remodeling: A Finite Element Analysis.

    Science.gov (United States)

    Pantoja, Joe Luis; Zhang, Zhihong; Tartibi, Mehrzad; Sun, Kay; Macmillan, Warrick; Guccione, Julius M; Ge, Liang; Ratcliffe, Mark B

    2015-12-01

    Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. VIRTUAL-DOR was associated with significant RS that was tensile (2.89 ± 1.31 kPa) in the remote myocardium and compressive (234.15 ± 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. A novel porcine model of early left ventricular dysfunction for translational research

    Directory of Open Access Journals (Sweden)

    Malik N

    2013-01-01

    Full Text Available Nadim Malik, Kelly A Farrell, Sarah B Withers, Elizabeth J Wright, Cathy M HoltInstitute for Cardiovascular Science, University of Manchester, Manchester, United KingdomBackground: The early stages of left ventricular (LV dysfunction account for a much larger proportion of the population with heart disease than that with clinical heart failure. However, LV dysfunction is more difficult to diagnose than established heart failure, and because of this it is not usually treated. Research on LV dysfunction is commonly conducted in small animal models in which the cardiac pathophysiology is dissimilar to that in humans, thereby restricting translation. This study aimed to use a novel pig model of mild to moderate early ischemic LV dysfunction to assess the effects of such dysfunction in the myocardium.Methods: Multiple areas of controlled microinfarcts were created via microembolization using embolization beads, with invasive hemodynamic and transthoracic echocardiographic assessment of LV function. Four weeks after intervention, the hearts were explanted for determination of the infarcted surface area and analysis of calcium regulatory proteins.Results: In vivo hemodynamic measurements confirmed a >25% decrease in LV dP/dt (maximum and minimum with creation of microinfarcts compared with baseline, whilst echocardiography showed mild to moderate LV dysfunction. Perioperative mortality was 10%–15%. In surviving pigs, morphometry at 4 weeks confirmed that up to 20% of the total LV surface area contained microinfarcts. Western blot analysis showed alterations in levels of the calcium regulatory proteins, sarcoplasmic reticulum Ca2+ ATPase and sodium-calcium exchange, in infarcted areas, compared with normal LV tissue from the same animals.Conclusion: These results demonstrate the usefulness of this model for investigation of the precise molecular and cellular changes associated with early mild to moderate LV dysfunction from ischemic injury, and its

  11. Rare Incidence of Ventricular Tachycardia and Torsades de Pointes in Hospitalized Patients With Prolonged QT Who Later Received Levofloxacin: A Retrospective Study.

    Science.gov (United States)

    Stancampiano, Fernando F; Palmer, William C; Getz, Trevor W; Serra-Valentin, Neysa A; Sears, Steven P; Seeger, Kristina M; Pagan, Ricardo J; Racho, Ronald G; Ray, Jordan C; Snipelisky, David F; Mentel, John J; Diehl, Nancy N; Heckman, Michael G

    2015-05-01

    To determine the incidence of ventricular tachycardia and ventricular fibrillation in patients with prolonged corrected QT interval (QTc) who received levofloxacin through retrospective chart review at a tertiary care teaching hospital in the United States. We selected 1004 consecutive hospitalized patients with prolonged QTc (>450 ms) between October 9, 2009 and June 12, 2012 at our institution. Levofloxacin was administered orally and/or intravenously and adjusted to renal function in the inpatient setting. The primary outcome measure was sustained ventricular tachycardia recorded electrocardiographically. With a median time from the start of levofloxacin use to hospital discharge (or death) of 4 days (range, 1-94 days), only 2 patients (0.2%; 95% CI, 0.0%-0.7%) experienced the primary outcome of sustained ventricular tachycardia after the initiation of levofloxacin use. In this study, the short-term risk for sustained ventricular tachycardia in patients with a prolonged QTc who subsequently received levofloxacin was very rare. These results suggest that levofloxacin may be a safe option in patients with prolonged QTc; however, studies with longer follow-up are needed. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  12. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting

    Science.gov (United States)

    Fernandez, Stanley F.; Ovchinnikov, Vladislav; Canty, John M.

    2013-01-01

    Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (−32%, P myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors. PMID:23125211

  13. Review of the emerging role of optical polarimetry in characterization of pathological myocardium.

    Science.gov (United States)

    Ahmad, Iftikhar

    2017-10-01

    Myocardial infarction (MI), a cause of significant morbidity and mortality, is typically followed by microstructural alterations where the necrotic myocardium is steadily replaced with a collagen scar. Engineered remodeling of the fibrotic scar via stem cell regeneration has been shown to improve/restore the myocardium function after MI. Nevertheless, the heterogeneous nature of the scar patch may impair the myocardial electrical integrity, leading to the formation of arrhythmogenesis. Radiofrequency ablation (RFA) offers an effective treatment for focal arrhythmias where local heating generated via electric current at specific spots in the myocardium ablate the arrhythmogenic foci. Characterization of these myocardial pathologies (i.e., infarcted, stem cell regenerated, and RFA-ablated myocardial tissues) is of potential clinical importance. Optical polarimetry, the use of light to map and characterize the polarization signatures of a sample, has emerged as a powerful imaging tool for structural characterization of myocardial tissues, exploiting the underlying highly fibrous tissue nature. This study aims to review the recent progress in optical polarimetry pertaining to the characterization of myocardial pathologies while describing the underlying biological rationales that give rise to the optical imaging contrast in various pathologies of the myocardium. Future possibilities of and challenges to optical polarimetry in cardiac imaging clinics are also discussed. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  14. Review of the emerging role of optical polarimetry in characterization of pathological myocardium

    Science.gov (United States)

    Ahmad, Iftikhar

    2017-10-01

    Myocardial infarction (MI), a cause of significant morbidity and mortality, is typically followed by microstructural alterations where the necrotic myocardium is steadily replaced with a collagen scar. Engineered remodeling of the fibrotic scar via stem cell regeneration has been shown to improve/restore the myocardium function after MI. Nevertheless, the heterogeneous nature of the scar patch may impair the myocardial electrical integrity, leading to the formation of arrhythmogenesis. Radiofrequency ablation (RFA) offers an effective treatment for focal arrhythmias where local heating generated via electric current at specific spots in the myocardium ablate the arrhythmogenic foci. Characterization of these myocardial pathologies (i.e., infarcted, stem cell regenerated, and RFA-ablated myocardial tissues) is of potential clinical importance. Optical polarimetry, the use of light to map and characterize the polarization signatures of a sample, has emerged as a powerful imaging tool for structural characterization of myocardial tissues, exploiting the underlying highly fibrous tissue nature. This study aims to review the recent progress in optical polarimetry pertaining to the characterization of myocardial pathologies while describing the underlying biological rationales that give rise to the optical imaging contrast in various pathologies of the myocardium. Future possibilities of and challenges to optical polarimetry in cardiac imaging clinics are also discussed.

  15. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    Science.gov (United States)

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  16. Subendocardial fibrosis in left ventricular hypertrabeculation-cause or consequence?

    Science.gov (United States)

    Ker, J; Du Toit-Prinsloo, L; Van Heerden, W F P; Saayman, G

    2011-02-02

    Left ventricular noncompaction has been classified as a primary cardiomyopathy with a genetic origin. This condition is morphologically characterized by a thickened, two-layered myocardium with numerous prominent trabeculations and deep, intertrabecular recesses. Recently, it has become clear that these pathological characteristics extend across a continuum with left ventricular hypertrabeculation at one end of the spectrum.The histological findings include areas of interstitial fibrosis.We present a case of left ventricular hypertrabeculation which presented as sudden infant death syndrome. Histologically areas of subendocardial fibrosis was prominent and we propose that this entity may be a hidden cause of arrhythmic death in some infants presenting as sudden infant death syndrome., with areas of subendocardial fibrosis as possible arrhythmogenic foci.

  17. Spinal cord stimulation reduces ventricular arrhythmias during acute ischemia by attenuation of regional myocardial excitability.

    Science.gov (United States)

    Howard-Quijano, Kimberly; Takamiya, Tatsuo; Dale, Erica A; Kipke, Jasmine; Kubo, Yukiko; Grogan, Tristan; Afyouni, Andyshea; Shivkumar, Kalyanam; Mahajan, Aman

    2017-08-01

    Myocardial ischemia creates autonomic nervous system imbalance and can trigger cardiac arrhythmias. We hypothesized that neuromodulation by spinal cord stimulation (SCS) will attenuate local cardiac sympathoexcitation from ischemia-induced increases in afferent signaling, reduce ventricular arrhythmias, and improve myocardial function during acute ischemia. Yorkshire pigs ( n = 20) were randomized to SCS (50 Hz at 200-μs duration, current 90% motor threshold) or sham operation (sham) for 30 min before ischemia. A four-pole SCS lead was placed percutaneously in the epidural space (T 1 -T 4 ), and a 56-electrode mesh was placed over the heart for high-resolution electrophysiological recordings, including activation recovery intervals (ARIs), activation time, repolarization time, and dispersion of repolarization. Electrophysiological and hemodynamic measures were recorded at baseline, after SCS/sham, during acute ischemia (300-s coronary artery ligation), and throughout reperfusion. SCS 1 ) reduced sympathoexcitation-induced ARI and repolarization time shortening in the ischemic myocardium; 2 ) attenuated increases in the dispersion of repolarization; 3 ) reduced ventricular tachyarrythmias [nonsustained ventricular tachycardias: 24 events (3 sham animals) vs. 1 event (1 SCS animal), P spinal cord stimulation decreased sympathetic nerve activation regionally in ischemic myocardium with no effect on normal myocardium, demonstrating that the antiarrhythmic effects of spinal cord stimulation are likely due to attenuation of local sympathoexcitation in the ischemic myocardium and not changes in global myocardial electrophysiology. Copyright © 2017 the American Physiological Society.

  18. Accuracy of contrast-enhanced cine-MR sequences in the assessment of left ventricular function: comparison with precontrast cine-MR sequences. Results of a bicentric study

    Energy Technology Data Exchange (ETDEWEB)

    Lasalarie, Jean-Christophe; Carre, Christophe [Centre Hospitalier Sud Reunion, Department of Radiology, Saint-Pierre (France); Serfaty, Jean-Michel; Schouman-Claeys, Elisabeth; Laissy, Jean-Pierre [Hopital Bichat AP-HP, Department of Radiology, Paris Cedex 18 (France); Messika-Zeitoun, David [Hopital Bichat, Department of Cardiology, Paris Cedex 18 (France); Jeannot, Christophe [Centre Hospitalier Sud Reunion, Department of Cardiology, Saint-Pierre (France)

    2007-11-15

    The accuracy of contrast-enhanced cine magnetic resonance (cine-MR) imaging to determine left ventricular function was assessed by comparison with the established noncontrast cine-MR sequences. Contrast-enhanced balanced steady-state free precession (cine-SSFP) sequences were compared with precontrast cine-SSFP sequences in the assessment of left ventricular contractile function in 30 consecutive patients with various cardiac diseases. Five to eight short-axis image sections were obtained in each patient. Quantitative data were analyzed using a paired t-test and linear regression analysis. Qualitative assessment of images was made following a 16-segment analysis. There was no significant difference between the two sequences in regional wall motion, end-diastolic volumes (EDV) and end-systolic volumes (ESV), stroke volume, left ventricular mass, as well as left ventricular ejection fraction (LVEF), despite slight delayed subendocardial enhancement in ten patients with myocardial infarction. All the values studied above were closely correlated between both cine-SSFP sequences (Spearman r=0.85-0.97, P<0.0001 for all comparisons). Contrast-enhanced cine-SSFP sequences can be used as a similar diagnostic tool as precontrast cine-MR sequences in the assessment of left ventricular contractile function. (orig.)

  19. Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: A European multicentre study

    Energy Technology Data Exchange (ETDEWEB)

    Bisi, G.; Sciagra, R. (Florence Univ. (Italy). Dipt. di Fisiopatologia Clinica); Buell, U. (Technische Hochschule Aachen (Germany, F.R.). Medizinische Fakultaet); Britton, K.E. (Saint Bartholomew' s Hospital, London (UK). Dept. of Nuclear Medicine); Eilles, C. (Luitpoldkrankenhaus, Wuerzburg (Germany, F.R.)); Eissner, D.; Hahn, K. (Mainz Univ. (Germany, F.R.). Klinikum); Hoeffken, H.; Joseph, K. (Marburg Univ. (Germany, F.R.). Klinikum); McKillop, J.H. (Royal Infirmary, Glasgow (UK). Dept. of Medicine); Larock, M.P.; Rigo, P. (Centre Hospitalier Universitaire Sart-Tilman, Tilman (Belgium). Service de Medecine Nucleaire); Mueller, S.P.; Reiners, C. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Klinikum)

    1991-03-01

    In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile ({sup 99m}Tc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfursion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r=0.909 (P<10{sup -6}), and in 22 cases with regard to the right ventricular ejection fraction, yielding r=0.712 (P<0.001). The comparison between the first-pass study using {sup 99m}Tc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P<10{sup -6}), and for the right ventricular ejection fraction in 15 subjects, with r=0.783 (P<0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of {sup 99m}Tc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of {sup 99m}Tc-Sestamibi. (orig.).

  20. Left Ventricular Longitudinal Systolic Function in Septic Shock Patients with Normal Ejection Fraction: A Case-control Study.

    Science.gov (United States)

    Zhang, Hong-Min; Wang, Xiao-Ting; Zhang, Li-Na; He, Wei; Zhang, Qing; Liu, Da-Wei

    2017-05-20

    Septic cardiomyopathy is a common finding in septic shock patients. The accepted definition of septic cardiomyopathy is often based on the left ventricular ejection fraction (LVEF). The aim of this study was to determine whether the left ventricular longitudinal systolic function was more sensitive than the LVEF in heart function appraisal of septic shock patients. This was a case-control study conducted at a 40-bed Intensive Care Unit (ICU) of Peking Union Medical College Hospital. Septic shock patients admitted to the ICU were consecutively enrolled in the study group from March 1, 2016 to September 1, 2016. The control group was selected from nonsepsis patients who were admitted to the ICU and were comparable to the study group. Transthoracic echocardiography was performed to obtain the LVEF measurement, mitral annular plane systolic excursion (MAPSE), tissue Doppler velocity measurement of mitral annulus (Sa), and tricuspid annular plane systolic excursion. The study group consisted of 45 septic shock patients. Another 45 nonsepsis patients were selected as the control group. There was no difference in the LVEF between the two groups (64.6% vs. 67.2%, t= -1.426, P= 0.161). MAPSE in the study group was much lower than in the control group (1.2 cm vs. 1.5 cm, t= -4.945, Pstudy group was also lower than in the control group (10.2 cm/s vs. 11.8 cm/s, t = -2.796, P= 0.014). Compared to the LVEF, longitudinal systolic function might be more sensitive in the detection of cardiac depression in septic shock patients. In the heart function appraisal of septic shock patients with a normal ejection fraction, more attention should be given to longitudinal function parameters such as MAPSE and Sa.

  1. Transmural heterogeneity of myofilament function and sarcomeric protein phosphorylation in remodeled myocardium of pigs with a recent myocardial infarction.

    Science.gov (United States)

    van der Velden, Jolanda; Merkus, Daphne; de Beer, Vincent; Hamdani, Nazha; Linke, Wolfgang A; Boontje, Nicky M; Stienen, Ger J M; Duncker, Dirk J

    2011-01-01

    Transmural differences in sarcomeric protein composition and function across the left ventricular (LV) wall have been reported. We studied in pigs sarcomeric function and protein phosphorylation in subepicardial (EPI) and subendocardial (ENDO) layers of remote LV myocardium after myocardial infarction (MI), induced by left circumflex coronary artery ligation. EPI and ENDO samples were taken 3 weeks after sham surgery (n = 12) or induction of MI (n = 12) at baseline (BL) and during β-adrenergic receptor (βAR) stimulation with dobutamine. Isometric force was measured in single cardiomyocytes at various [Ca(2+)] and 2.2 μm sarcomere length. In sham hearts, no significant transmural differences were observed in myofilament function or protein phosphorylation. Myofilament Ca(2+)-sensitivity was significantly higher in both EPI and ENDO of MI compared to sham hearts. Maximal force was significantly reduced in MI compared to sham, but solely in ENDO cells. A higher passive force was observed in MI hearts, but only in EPI cells. The proportion of stiff N2B isoform was higher in EPI than in ENDO in both sham and MI hearts, and a trend toward increased N2B-proportion appeared in MI EPI, but not MI Endo. Analysis of myofilament protein phosphorylation did not reveal significant transmural differences in phosphorylation of myosin binding protein C, desmin, troponin T, troponin I (cTnI), and myosin light chain 2 (MLC-2) both at BL and during βAR stimulation with dobutamine infusion. A significant increase in MLC-2 phosphorylation was observed during dobutamine only in sham. In addition, the increase in cTnI phosphorylation upon dobutamine was twofold lower in MI than in sham. Myofilament dysfunction is present in both EPI and ENDO in post-MI remodeled myocardium, but shows a high degree of qualitative heterogeneity across the LV wall. These heterogeneous transmural changes in sarcomeric properties likely contribute differently to systolic vs. diastolic global LV

  2. An Experimental Model Using Cultured Cardiac Myocytes for a Study of the Generation of Premature Ventricular Contractions Under Ultrasound Exposure

    Science.gov (United States)

    Kudo, Nobuki; Yamamoto, Masaya

    2011-09-01

    It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.

  3. Exercise and cardiovascular outcomes in hypertensive patients in relation to structure and function of left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Boman, Kurt; Gerdts, Eva; Wachtell, Kristian

    2009-01-01

    BACKGROUND: Exercise lowers blood pressure and improves cardiovascular function, but little is known about whether exercise impacts cardiovascular morbidity and mortality independent of left ventricular hypertrophy (LVH) and LV geometry. DESIGN: Observational analysis of prospectively obtained...... (never exercise), intermediate (30 min twice/week). During 4.8-year follow-up, 105 patients suffered the primary composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death. MI occurred in 39, stroke in 60, and cardiovascular death in 33 patients. RESULTS: Sedentary individuals (n...... echocardiographic data within the context of a randomized trial of antihypertensive treatment. METHODS: A total of 937 hypertensive patients with ECG LVH were studied by echocardiography in the Losartan Intervention For Endpoint reduction in hypertension study. Baseline exercise status was categorized as sedentary...

  4. Contrast Circulation Time to Assess Right Ventricular Dysfunction in Pulmonary Embolism: A Retrospective Pilot Study.

    Science.gov (United States)

    John, Gregor; Platon, Alexandra; Poletti, Pierre-Alexandre; Perrier, Arnaud; Bendjelid, Karim

    2016-01-01

    To optimize enhancement of pulmonary arteries and facilitate diagnosis of pulmonary embolism (PE), modern computed tomography angiography (CTA) contains a contrast bolus tracking system. We explored the diagnostic accuracy of the time-intensity curves given by this automated system to identify right ventricular dysfunction (RVD) in acute PE. 114 CTAs with a diagnosis of PE were reviewed. RVD was defined as right-to-left ventricular diameter ratio of 1 or greater. Four parameters on time-intensity curves were identified. Parameters between CTAs with and those without RVD were compared with the Wilcoxon rank-sum test. The ability of the four parameters to discriminate patients with RVD was explored by compiling the area under the operating curves (AUC). The time needed by the contrast media to reach the pulmonary artery [8 seconds (IQR: 7-9) versus 7 seconds (IQR: 6-8), p<0.01], the time needed to reach 40 Hounsfield units (HU) [11 seconds (IQR: 8.5-14) versus 9.5 seconds (IQR: 8-10.5), p<0.01], and the contrast intensity reached after 10 seconds [19 HU (IQR: 4-67) versus 53 HU (IQR: 32-80), p<0.05] were all statistically different between CTA with and CTA without RVD. Those three parameters changed gradually across severity categories of RVD (p<0.05 for trend). Their AUC to identify RVD ranged from 0.63 to 0.66. The slope of contrast intensity over time was not informative: [31 HU/s (IQR: 20-57) in CTA with, compared to 36 HU/s (IQR: 22.5-53) in CTA without RVD, p = 0.60]. Several parameters of the time-intensity curve obtained by the bolus tracking system are associated with RVD assessed on CTA images. Of those, the time needed to reach a predefined threshold seems to be the easiest to obtain in any CTA without additional processing time or contrast injection. However, the performance of those parameters is globally low.

  5. Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

    Science.gov (United States)

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; Crandon, Saul; Chew, Pei G; van der Geest, R J; Greenwood, John P; Plein, Sven

    2017-09-25

    Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

  6. Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy.

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    Mireia Alcalde

    Full Text Available BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC is a cardiac disease characterized by the presence of fibrofatty replacement of the right ventricular myocardium, which may cause ventricular arrhythmias and sudden cardiac death. Pathogenic mutations in several genes encoding mainly desmosomal proteins have been reported. Our aim is to perform genotype-phenotype correlations to establish the diagnostic value of genetics and to assess the role of mutation type in age-related penetrance in ARVC. METHODS AND RESULTS: Thirty unrelated Spanish patients underwent a complete clinical evaluation. They all were screened for PKP2, DSG2, DSC2, DSP, JUP and TMEM43 genes. A total of 70 relatives of four families were also studied. The 30 patients fulfilled definite disease diagnostic criteria. Genetic analysis revealed a pathogenic mutation in 19 patients (13 in PKP2, 3 in DSG2, 2 in DSP, and 1 in DSC2. Nine of these mutations created a truncated protein due to the generation of a stop codon. Familial assessment revealed 28 genetic carriers among family members. Stop-gain mutations were associated to a later age of onset of ARVC, without differences in the severity of the pathology. CONCLUSIONS: Familial genetic analysis helps to identify the cause responsible for the pathology. In discrepancy with previous studies, the presence of a truncating protein does not confer a worse severity. This information could suggest that truncating proteins may be compensated by the normal allele and that missense mutations may act as poison peptides.

  7. Ventricular arrhythmias in Chagas disease

    Directory of Open Access Journals (Sweden)

    Marco Paulo Tomaz Barbosa

    2015-02-01

    Full Text Available Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

  8. Mitochondrial adaptations within chronically ischemic swine myocardium.

    Science.gov (United States)

    McFalls, Edward O; Sluiter, Wim; Schoonderwoerd, Kees; Manintveld, Olivier C; Lamers, Jos M J; Bezstarosti, Karel; van Beusekom, Heleen M; Sikora, Joseph; Ward, Herbert B; Merkus, Daphne; Duncker, Dirk J

    2006-12-01

    Experimental evidence has emerged that myocardial ischemic preconditioning can prime the mitochondria into a "stress-resistant state", so that cell death is reduced following prolonged severe ischemia and reperfusion. Using a swine model of chronically ischemic myocardium, we tested the hypothesis that mitochondria within the ischemic territory have also acquired a protective phenotype. Eleven swine underwent a left thoracotomy with placement of an external constrictor around the proximal left anterior descending (LAD) artery. By 10 weeks, a severe stenosis of the LAD artery was documented by quantitative coronary angiography (92 +/- 2%). Animals were sacrificed and myocardium was extracted from the LAD and remote regions. Mitochondria were isolated from subendocardium and subepicardium from LAD and remote regions and state 2 (substrate alone) and state 3 (+ADP) respiration were assessed with a Clark electrode. Within the LAD subendocardium, the respiratory control index was 2.68 +/- 0.17 and was lower than the remote subendocardium (3.64 +/- 0.08; P < 0.05). When exposed to 20 min anoxia with reoxygenation, the LAD region demonstrated a more preserved state 3 respiration compared with the remote region (99 +/- 14 versus 65 +/- 9 nmol O2/mg, respectively; P < 0.05). In parallel mitochondrial experiments, chemiluminescence was detected with the probe coelenterazine and superoxide generation in the LAD region in the presence of antimycin A was 574 +/- 108 RLU/30 s/microg and was nearly 50% lower than the remote region (979 +/- 175 RLU/30 s/microg; P < 0.05). Within the mitochondria, the expression of uncoupling protein (UCP) 2 by western gels was 20% higher in the LAD region compared with the remote region (P < 0.05) with no differences noted in UCP-3. In this swine model of chronic myocardial ischemia, isolated mitochondria from the ischemic tissue demonstrate preserved state 3 respiration following anoxia/reoxygenation, consistent with a stress-resistant state

  9. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium

    Science.gov (United States)

    Turnbull, Irene C.; Karakikes, Ioannis; Serrao, Gregory W.; Backeris, Peter; Lee, Jia-Jye; Xie, Chaoqin; Senyei, Grant; Gordon, Ronald E.; Li, Ronald A.; Akar, Fadi G.; Hajjar, Roger J.; Hulot, Jean-Sébastien; Costa, Kevin D.

    2014-01-01

    Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18±0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 μN/mm2 at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 μM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.—Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J.-J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J.-S., Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. PMID:24174427

  10. Revascularization of chronic hibernating myocardium stimulates myocyte proliferation and partially reverses chronic adaptations to ischemia.

    Science.gov (United States)

    Page, Brian J; Banas, Michael D; Suzuki, Gen; Weil, Brian R; Young, Rebeccah F; Fallavollita, James A; Palka, Beth A; Canty, John M

    2015-02-24

    The time course and extent of recovery after revascularization of viable dysfunctional myocardium are variable. Although fibrosis is a major determinant, myocyte structural and molecular remodeling may also play important roles. This study sought to determine whether persistent myocyte loss and/or irreversibility of protein changes that develop in hibernating myocardium have an impact on functional recovery in the absence of infarction. Swine implanted with a chronic left anterior descending artery (LAD) stenosis to produce hibernating myocardium underwent percutaneous revascularization, with serial functional recovery evaluated for 1 month (n = 12). Myocardial tissue was evaluated to assess myocyte size, nuclear density, and proliferation indexes in comparison with those of normal animals and nonrevascularized controls. Proteomic analysis by 2-dimensional differential in-gel electrophoresis was used to determine the reversibility of molecular adaptations of hibernating myocytes. At 3 months, physiological features of hibernating myocardium were confirmed, with depressed LAD wall thickening and no significant infarction. Revascularization normalized LAD flow reserve, with no immediate change in LAD wall thickening. Regional LAD wall thickening slowly improved but remained depressed 1 month post-percutaneous coronary intervention. Surprisingly, revascularization was associated with histological evidence of myocytes re-entering the growth phase of the cell cycle and increases in the number of c-Kit(+) cells. Myocyte nuclear density returned to normal, whereas regional myocyte hypertrophy regressed. Proteomic analysis demonstrated heterogeneous effects of revascularization. Up-regulated stress and cytoskeletal proteins normalized, whereas reduced contractile and metabolic proteins persisted. Delayed recovery of hibernating myocardium in the absence of scar may reflect persistent reductions in the amounts of contractile and metabolic proteins. Although

  11. Revascularization of Chronic Hibernating Myocardium Stimulates Myocyte Proliferation and Partially Reverses Chronic Adaptations to Ischemia

    Science.gov (United States)

    Page, Brian J.; Banas, Michael D.; Suzuki, Gen; Weil, Brian R.; Young, Rebeccah F.; Fallavollita, James A.; Palka, Beth A.; Canty, John M.

    2014-01-01

    Background The time course and extent of recovery after revascularization of viable dysfunctional myocardium is variable. While fibrosis is a major determinant, myocyte structural and molecular remodeling may also play important roles. Objective This study sought to determine whether persistent myocyte loss and/or irreversibility of protein changes that develop in hibernating myocardium have an impact on functional recovery in the absence of infarction. Methods Swine instrumented with a chronic left anterior descending artery (LAD) stenosis to produce hibernating myocardium underwent percutaneous revascularization with serial functional recovery evaluated for 1 month (n = 12). Myocardial tissue was evaluated to assess myocyte size, nuclear density, and proliferation indexes in comparison to normal animals and nonrevascularized controls. Proteomic analysis by 2-dimensional differential in-gel electrophoresis (2D-DIGE) was used to determine the reversibility of molecular adaptations of hibernating myocytes. Results At 3 months, physiological features of hibernating myocardium were confirmed, with depressed LAD wall thickening and no significant infarction. Revascularization normalized LAD flow reserve, with no immediate change in LAD wall thickening. Regional LAD wall thickening slowly improved, but remained depressed 1 month post-percutaneous coronary intervention (PCI). Surprisingly, revascularization was associated with histological evidence of myocytes reentering the growth phase of the cell cycle and increased cKit+ cells. Myocyte nuclear density returned to normal, while regional myocyte hypertrophy regressed. Proteomic analysis demonstrated heterogeneous effects of revascularization. Up-regulated stress and cytoskeletal proteins normalized, while reduced contractile and metabolic proteins persisted. Conclusions Delayed recovery of hibernating myocardium in the absence of scar may reflect persistent reductions in contractile and metabolic proteins. While

  12. Relation between left ventricular outflow tract obstruction and left ventricular shape in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Martin, Romain; Lairez, Olivier; Boudou, Nicolas; Méjean, Simon; Lhermusier, Thibault; Dumonteil, Nicolas; Berry, Matthieu; Cognet, Thomas; Massabuau, Pierre; Elbaz, Meyer; Rousseau, Hervé; Galinier, Michel; Carrié, Didier

    2013-01-01

    Hypertrophic cardiomyopathies (HCM) are often associated with left ventricular (LV) outflow tract obstruction, which can explain symptoms and impact prognosis. To better understand the mechanisms that link obstruction and LV shape in HCM. Patients with HCM who underwent cardiac magnetic resonance (CMR) imaging were included retrospectively. Obstructive HCM was defined as LV outflow gradient more than 30 mm Hg at rest by transthoracic echocardiography. The LV shape and mitral angle were assessed by CMR. Results were compared with control subjects. Mean LV-mitral angle was smaller in patients with obstructive HCM (n=29) than in patients with non-obstructive HCM (n=15) or control subjects (n=15) (80 ± 5° vs 87 ± 7° [P=0.0002] and 89 ± 2° [P<0.0001]). Mean mitral papillary muscles angle was greater in patients with non-obstructive HCM than in patients with obstructive HCM or control subjects (136 ± 17° vs 123 ± 16° [P=0.007] and 118 ± 10° [P=0.002]). Patients with non-obstructive HCM had a greater mean LV-aortic root angle than patients with obstructive HCM or control subjects (139 ± 6° vs 135 ± 7° [P=0.04] and 133 ± 7° [P=0.03]). There is a relation between morphological and functional parameters in HCM within which the mitral valve is probably part of pathophysiogenesis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Long-term prognostic importance of resting heart rate in patients with left ventricular dysfunction in connection with either heart failure or myocardial infarction: the DIAMOND study

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Seibaek, Marie; Brendorp, Bente

    2010-01-01

    dysfunction in connection with either heart failure (HF) or myocardial infarction (MI). METHODS: In the Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study; patients with left ventricular dysfunction were randomized to Dofetilide (class III antiarrhythmic drug) or placebo. One part of the study...

  14. Transient and quasi-steady computational fluid dynamics study of a left ventricular assist device.

    Science.gov (United States)

    Song, Xinwei; Throckmorton, Amy L; Wood, Houston G; Allaire, Paul E; Olsen, Don B

    2004-01-01

    The HeartQuest continuous flow left ventricle assist device (LVAD) with a magnetically levitated impeller operates under highly transient flow conditions. Due to insertion of the in-flow cannula into the apex of the left ventricle, the inlet flow rate is transient because of ventricular contraction, and the pump's asymmetric circumferential configuration with five rotating blades forces blood intermittently through the pump to the great arteries. These two transient conditions correspond to time varying boundary conditions and transient rotational sliding interfaces in computational fluid dynamics (CFD). CFD was used to investigate the pump's performance under these dynamic flow conditions. A quasi-steady analysis was also conducted to evaluate the difference between the steady and transient analyses and demonstrate the significance of transient analysis, especially for transient rotational sliding interfaces transient simulations. This transient flow analysis can be applied generally in the design process of LVADs; it provides more reliable fluid forces and moments on the impeller for successful design of the magnetic suspension system and motor.

  15. Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

    Science.gov (United States)

    Odening, Katja E.; Kirk, Malcolm; Brunner, Michael; Ziv, Ohad; Lorvidhaya, Peem; Liu, Gong Xin; Schofield, Lorraine; Chaves, Leonard; Peng, Xuwen; Zehender, Manfred; Choi, Bum-Rak

    2010-01-01

    We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K+ current [IKs; long QT syndrome type 1 (LQT1)] or rapidly activating delayed-rectifier K+ current [IKr; long QT syndrome type 2 (LQT2)]. Rabbits with either genotype have prolonged action potential duration and QT intervals; however, only LQT2 rabbits develop atrioventricular (AV) blocks and polymorphic ventricular tachycardia. We therefore sought to characterize the genotype-specific differences in AV conduction and ventricular refractoriness in LQT1 and LQT2 rabbits. We carried out in vivo electrophysiological studies in LQT1, LQT2, and littermate control (LMC) rabbits at baseline, during isoproterenol infusion, and after a bolus of dofetilide and ex vivo optical mapping studies of the AV node/His-region at baseline and during dofetilide perfusion. Under isoflurane anesthesia, LQT2 rabbits developed infra-His blocks, decremental His conduction, and prolongation of the Wenckebach cycle length. In LQT1 rabbits, dofetilide altered the His morphology and slowed His conduction, resulting in intra-His block, and additionally prolonged the ventricular refractoriness, leading to pseudo-AV block. The ventricular effective refractory period (VERP) in right ventricular apex and base was significantly longer in LQT2 than LQT1 (P rabbits. Isoproterenol reduced the VERP dispersion in LQT2 rabbits by shortening the VERP in the base more than in the apex but had no effect on VERP in LQT1. EPS and optical mapping experiments demonstrated genotype-specific differences in AV conduction and ventricular refractoriness. The occurrence of infra-His blocks in LQT2 rabbits under isoflurane and intra-His block in LQT1 rabbits after dofetilide suggest differential regional sensitivities of the rabbit His-Purkinje system to drugs blocking IKr and IKs. PMID:20581090

  16. The association of sleep disordered breathing with left ventricular remodeling in CAD patients: a cross-sectional study.

    Science.gov (United States)

    Alonderis, Audrius; Raskauskiene, Nijole; Gelziniene, Vaidute; Mickuviene, Narseta; Brozaitiene, Julija

    2017-09-18

    There is still insufficient knowledge on the potential effect of mild to moderate sleep-disordered breathing (SDB) that is widely prevalent, often asymptomatic, and largely undiagnosed in patients with stable coronary artery disease (CAD). SDB affects 34% of men and 17% of women aged between 30 and 70. The objective of this study was to evaluate the association between SDB and left ventricular (LV) hypertrophy as well as structural remodeling in stable CAD patients. The study was based on a cross-sectional design. Echocardiography and polysomnography was performed in 772 patients with CAD and with untreated sleep apnea. All study participants underwent testing by Epworth Sleepiness Scale questionnaire. Their mean age, NYHA and left ventricular ejection fraction were, respectively: 57 ± 9 years, 2.1 ± 0.5 and 51 ± 8%, and 76% were men. Sleep apnea (SA) was defined as an apnea-hypopnea-index (AHI) ≥5 events/h, and, non-SA, as an AHI CAD patients with SA. The patients with SA had significantly higher values of both interventricular septal thickness and posterior wall thickness. Multiple logistic regression analysis showed that even mild sleep apnea was an independent predictor for LVH by wall thickness criteria and concentric LVH (OR = 1.5; 95% CI 1.04-2.2 and OR = 1.9; 1.3-2.9 respectively). We concluded that unrecognized sleep apnea was highly prevalent among patients with stable CAD, and the majority of those patients did not report daytime sleepiness. Mild to moderate sleep apnea was associated with increased LV wall thickness, LV mass, and with higher prevalence of concentric LV hypertrophy independently of coexisting obesity, hypertension, diabetes mellitus or advancing age.

  17. Estudo da sístole elétrica ventricular nos insuficientes renais crônicos hemodialisados Study of ventricular electrical systole in patients with end-stage kidney disease on hemodialysis

    Directory of Open Access Journals (Sweden)

    Bruno Valentim

    2013-03-01

    and intermittent character of dialysis. Changes in ventricular electrical systole induced by necessary dialysis significantly contribute to predict sudden death due to arrhythmia in ESKD. OBJECTIVE: The major objective of this study was to assess the behavior of ventricular repolarization in dialysis by analyzing QTc interval and QTc dispersion. METHODS: This study sample consisted of 47 patients undergoing hemodialysis (61.7% males and 38.3% females, whose mean age was 66.79±13.16 years. All of them underwent three electrocardiograms performed before, during and after one dialysis session. Ventricular electrical systole was analyzed later. RESULTS: An increase in maximum QTc interval and QTc dispersion associated with dialysis was observed. In addition, an increase in the number of individuals meeting the electrocardiographic criteria for left ventricular hypertrophy (LVH was observed. After dialysis, higher means of the maximum QTc interval (473 ± 27.63 mseg and of the QTc dispersion (58.95 ± 18.87 mseg were observed in individuals with LVH as compared with those in individuals without LVH (455.21 ± 26.85 mseg and 44 ± 16.41 mseg, respectively. CONCLUSION: This study confirmed an increase in the QTc interval and QTc dispersion associated with dialysis. That emphasizes the dependence of ventricular repolarization on fluid and electrolyte balance, and suggests a profile of higher vulnerability to arrhythmia associated with dialysis .

  18. Aerodynamic and acoustic effects of ventricular gap.

    Science.gov (United States)

    Alipour, Fariborz; Karnell, Michael

    2014-03-01

    Supraglottic compression is frequently observed in individuals with dysphonia. It is commonly interpreted as an indication of excessive circumlaryngeal muscular tension and ventricular medialization. The purpose of this study was to describe the aerodynamic and acoustic impact of varying ventricular medialization in a canine model. Subglottal air pressure, glottal airflow, electroglottograph, acoustic signals, and high-speed video images were recorded in seven excised canine larynges mounted in vitro for laryngeal vibratory experimentation. The degree of gap between the ventricular folds was adjusted and measured using sutures and weights. Data were recorded during phonation when the ventricular gap was narrow, neutral, and large. Glottal resistance was estimated by measures of subglottal pressure and glottal flow. Glottal resistance increased systematically as ventricular gap became smaller. Wide ventricular gaps were associated with increases in fundamental frequency and decreases in glottal resistance. Sound pressure level did not appear to be impacted by the adjustments in ventricular gap used in this research. Increases in supraglottic compression and associated reduced ventricular width may be observed in a variety of disorders that affect voice quality. Ventricular compression may interact with true vocal fold posture and vibration resulting in predictable changes in aerodynamic, physiological, acoustic, and perceptual measures of phonation. The data from this report supports the theory that narrow ventricular gaps may be associated with disordered phonation. In vitro and in vivo human data are needed to further test this association. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  19. Clinical impact of ' in-treatment' wall motion abnormalities in hypertensive patients with left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    Cicala, S.; Simone, G. de; Wachtell, K.

    2008-01-01

    In hypertensive patients with LVH and no history of cardiovascular disease, ' in- treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in- treatment left......, however, never been investigated. We examined whether 'in- treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint ( LIFE) reduction in hypertension echocardiographic substudy. Methods We studied 749 patients without coronary artery disease, myocardial infarction...... to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure. Results During a mean follow-up of 4.8 years, an event was recorded in 67 ( 9%) patients. In Cox models after adjusting for age, gender, treatment, blood...

  20. Epidemiology of Left Ventricular Systolic Dysfunction and Heart Failure in the Framingham Study

    DEFF Research Database (Denmark)

    Vasan, Ramachandran S; Xanthakis, Vanessa; Lyass, Asya

    2018-01-01

    OBJECTIVES: The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation. BACKGROUND: Temporal trends in the prevalence...... with LVSD (∼2- to 4-fold risk of HF or death) remained unchanged over time. Among participants with new-onset HF (n = 894, mean age 75 years, 52% women), the frequency of heart failure with preserved ejection fraction (HFpEF) increased (preserved LVEF ≥50%: 41.0% in 1985 to 1994 vs. 56.17% in 2005 to 2014......; p heart failure with reduced ejection fraction (HFrEF) decreased (reduced LVEF heart failure with midrange LVEF remained unchanged (LVEF 40% to

  1. Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

    Directory of Open Access Journals (Sweden)

    Bortolo Martini

    2015-01-01

    Full Text Available A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT. ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches.

  2. Toll-like receptor 4 mediates the inflammatory responses and matrix protein remodeling in remote non-ischemic myocardium in a mouse model of myocardial ischemia and reperfusion.

    Science.gov (United States)

    Zhai, Yufeng; Ao, Lihua; Cleveland, Joseph C; Zeng, Qingchun; Reece, T Brett; Fullerton, David A; Meng, Xianzhong

    2015-01-01

    The signaling mechanism that mediates inflammatory responses in remote non-ischemic myocardium following regional ischemia/reperfusion (I/R) remains incompletely understood. Myocardial Toll-like receptor 4 (TLR4) can be activated by multiple proteins released from injured cells and plays a role in myocardial inflammation and injury expansion. We tested the hypothesis that TLR4 occupies an important role in mediating the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional I/R injury. TLR4-defective (C3H/HeJ) and TLR4-competent (C3H/HeN) mice were subjected to coronary artery ligation (30 min) and reperfusion for 1, 3, 7 or 14 days. In TLR4-competent mice, levels of monocyte chemoattractant protein -1 (MCP-1), keratinocyte chemoattractant (KC), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were elevated in the remote non-ischemic myocardium at day 1, 3, and 7 of reperfusion. Levels of collagen I, collagen IV, matrix metalloproteinase (MMP) 2 and MMP 9 were increased in the remote non-ischemic myocardium at day 7 and 14 of reperfusion. MMP 2 and MMP 9 activities were also increased. TLR4 deficiency resulted in a moderate reduction in myocardial infarct size. However, it markedly downgraded the changes in the levels of chemokines, adhesion molecules and matrix proteins in the remote non-ischemic myocardium. Further, left ventricular function at day 14 was significantly improved in TLR4-defective mice. In conclusion, TLR4 mediates the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional myocardial I/R injury and contributes to the mechanism of adverse cardiac remodeling.

  3. Safety and efficacy of a dual chamber implantable cardioverter defibrillator capable of slow ventricular tachycardia discrimination: a randomized study.

    Science.gov (United States)

    Mletzko, Ralph; Aliot, Etienne; Seidl, Karlheinz; Lavergne, Thomas; Mabo, Philippe; Hohnloser, Stefan; Bocker, Dirk; Schoels, Wolfgang; Sadoul, Nicolas

    2003-12-01

    New developments in dual chamber implantable cardioverter defibrillators (ICD) have increased the specificity of therapy delivery. This study was performed to examine the performance of an algorithm, focusing on its ability to distinguish slow ventricular tachycardia (VT) from sinus rhythm or supraventricular tachyarrhythmias. The patient population included 77 men and 13 women, 63 +/- 11 years old, treated with ICDs after episodes of spontaneous or inducible ventricular tachyarrhythmias. They were randomized to programming of the ICD to a lower limit of VT detection at 128 beats/min (group I, n = 44), versus 153 beats/min II (group II, n = 46). The primary endpoint of the study consisted of comparing the specificity and sensitivity of the algorithm between the two groups of patients. Over a 10.1 +/- 3.5 months follow-up, 325 episodes were detected in the Tachy zone in group I, versus 106 in group II. The sensitivity and specificity of the algorithm in group I were 98.8% and 94.4%, respectively, versus 100% and 89% in group II (NS). A single episode of VT at a rate of 132 beats/min was diagnosed as SVT in group I. The sensitivity and specificity of the algorithm for tachycardias <153 beats/min were 97.4% and 94.5%, respectively. Overall VT therapy efficacy was 100% in both groups. The performance of this algorithm in the slow VT zone supports the programming of a long Tachy detection interval to document slow events, and allows to treat slow VT, if necessary, without significant risk of inappropriate interventions for sinus tachycardia.

  4. Cardiac Telocytes in Regeneration of Myocardium After Myocardial Infarction.

    Science.gov (United States)

    Zhaofu, Liao; Dongqing, Cai

    2016-01-01

    Recent research progress has revealed that a novel type of interstitial cells termed cardiac telocytes (CTs) is found in the interstitium of the heart. We demonstrated that CTs are distributed both longitudinally and within the cross network in the myocardium and that the density of CTs in the atrium-atria and base of the myocardium is higher than that in the middle of the myocardium, while the density of CTs in the epicardium is higher than that in the endocardium. In addition, we documented, for the first time, that the network of CTs in the infarct zone of the myocardium is destroyed during myocardial infarction (MI). This fact shows that, in addition to the death of cardiac myocytes, the previously unrecognized death of CTs is an important mechanism that contributes to the structural damage and poor healing and regeneration observed in the infarcted myocardium. Furthermore, we demonstrated, for the first time, that transplantation of CTs in cases of MI decreases the infarct size and improves myocardial function. The mechanisms behind the beneficial effects of CT transplantation are increased angiogenesis at the infarct site and the border zone, decreased fibrosis in the infarct and non-infarct zones, improved pathological reconstruction of the left ventricle, and increased regeneration of CTs in the infarct zone. Our findings reveal that CTs can be specifically identified by the following characteristics: very small cell bodies, extreme prolongation with some dilation, predisposition to cell death under ischemia, and expression of molecular markers such as c-Kit, CD34, vimentin, and PDGFR-β. CTs act as a structural and functional niche microenvironment in the myocardium and play an essential role in maintaining the integrity of the myocardium and in the regeneration of damaged myocardium.

  5. Assessment of Structural and Functional Abnormalities of the Myocardium and the Ascending Aorta in Fetus with Hypoplastic Left Heart Syndrome

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2016-01-01

    Full Text Available Aims. To detect anatomical and intrinsic histopathological features of the ascending aorta and left ventricular (LV myocardium and evaluate right ventricular (RV function in fetuses with hypoplastic left heart syndrome (HLHS. Methods. Twenty-five fetuses diagnosed with HLHS were followed up in the antenatal and postpartum periods. 12 necropsy heart specimens were analyzed for morphological and histological changes. Results. Prenatal echocardiography and pathologic anatomy displayed the typical characteristics of HLHS as a severe underdevelopment of the LV in the form of mitral stenosis or atresia or as aortic atresia or stenosis, with a decreased ratio of aortic diameter to pulmonary artery diameter (median of 0.49 with a range of 0.24 to 0.69, p≤0.001 and a higher ratio of RV diameter to LV diameter (median of 2.44 with a range of 1.33 to 6.25, p≤0.001. The RV volume, stroke volume, and cardiac output in HLHS fetuses were increased compared with the gestational age-matched normal controls (p<0.01. Histological changes in the 12 HLHS specimens included LV myocardial fibrosis, aortic elastic fragmentation, and fibrosis. Conclusions. In addition to severe anatomical deformity, distinct histological abnormalities in the LV myocardium and aortic wall were identified in the fetuses with HLHS. RV function damage may be potentially exists.

  6. Assessment of Structural and Functional Abnormalities of the Myocardium and the Ascending Aorta in Fetus with Hypoplastic Left Heart Syndrome

    Science.gov (United States)

    Jiang, Yan; Xu, Yali; Tang, Jinliang; Xia, Hongmei

    2016-01-01

    Aims. To detect anatomical and intrinsic histopathological features of the ascending aorta and left ventricular (LV) myocardium and evaluate right ventricular (RV) function in fetuses with hypoplastic left heart syndrome (HLHS). Methods. Twenty-five fetuses diagnosed with HLHS were followed up in the antenatal and postpartum periods. 12 necropsy heart specimens were analyzed for morphological and histological changes. Results. Prenatal echocardiography and pathologic anatomy displayed the typical characteristics of HLHS as a severe underdevelopment of the LV in the form of mitral stenosis or atresia or as aortic atresia or stenosis, with a decreased ratio of aortic diameter to pulmonary artery diameter (median of 0.49 with a range of 0.24 to 0.69, p ≤ 0.001) and a higher ratio of RV diameter to LV diameter (median of 2.44 with a range of 1.33 to 6.25, p ≤ 0.001). The RV volume, stroke volume, and cardiac output in HLHS fetuses were increased compared with the gestational age-matched normal controls (p < 0.01). Histological changes in the 12 HLHS specimens included LV myocardial fibrosis, aortic elastic fragmentation, and fibrosis. Conclusions. In addition to severe anatomical deformity, distinct histological abnormalities in the LV myocardium and aortic wall were identified in the fetuses with HLHS. RV function damage may be potentially exists. PMID:26981527

  7. Evaluation of Longitudinal Right Ventricular Mechanical Dyssynchrony before and Early after Cardiac Resynchronization Therapy: A Strain Imaging Study

    Directory of Open Access Journals (Sweden)

    Mozhgan Parsaee

    2011-02-01

    Full Text Available Background: The right ventricular (RV dyssynchrony has not been studied extensively and the existing literature has established the effect of cardiac resynchronization therapy (CRT on the left ventricular (LV dyssynchrony, but there is a dearth of data on the effect of CRT on the forgotten ventricle. We sought to evaluate the presence of mechanical right ventricular dyssynchrony in patients with systolic heart failure, selected for CRT, and track the changes early afterward utilizing the longitudinal strain analysis.Methods: Thirty-six patients with severe left ventricular systolic dysfunction, candidated for CRT, were enrolled in this study. Mechanical dyssynchrony was assessed using tissue Doppler echocardiography. The time interval between the onset of the QRS to the peak systolic longitudinal strain at the RV free wall and the septum was obtained. The RV mechanical delay was calculated as the absolute value of the difference in the time-to-peak measurements between the RV and septum. The RV dyssynchrony was defined as the calculated delay in strain imaging, which was ± 2 SD above the mean value for the control subjects (20 cases. The RV function was evaluated using the RV fractional area change (RVFAC, tricuspid annulus plane systolic excursion (TAPSE, and peak systolic strain values of the RV free wall. Four to 7 days after CRT implantation, echocardiographic reevaluations were done.Results: The calculated cut-off value for the RV dyssynchrony was 41.5 msec, according to which the pre-CRT analysis specified two patient groups: Group 1 (16 cases with RV dyssynchrony and Group 2 (20 patients without RV dyssynchrony. Significant improvement in the RV dyssynchrony was noted in Group 1 after CRT (30 ± 28.9 msec vs. 68.8 ± 21 msec; p value < 0.01 vs. 14 ± 10 msec vs. 19 ± 16.5 msec; p value = 0.18 respectively. A significant correlation was found between the severity of the RV dyssynchrony and peak systolic strain in the RV free wall (r = -0

  8. Temporal change of myocardial tissue character is associated with left ventricular reverse remodeling in patients with dilated cardiomyopathy: A cardiovascular magnetic resonance study.

    Science.gov (United States)

    Nabeta, Takeru; Inomata, Takayuki; Fujita, Teppei; Iida, Yuichiro; Ikeda, Yuki; Sato, Takanori; Ishii, Shunsuke; Maekawa, Emi; Mizutani, Tomohiro; Naruke, Takashi; Koitabashi, Toshimi; Inoue, Yusuke; Ako, Junya

    2017-08-01

    Prognostic significance of temporal change in myocardial tissue characterization by cardiovascular magnetic resonance (CMR) has not been elucidated in patients with non-ischemic dilated cardiomyopathy (DCM). Sixty-eight patients with newly-diagnosed DCM who underwent CMR including late gadolinium enhancement (LGE) both at baseline and during follow-up period were enrolled. LGE score was defined by a signal intensity of ≥5 standard deviations above the remote reference myocardium mean. Left ventricular reverse remodeling (LVRR) defined as a LV ejection fraction increase of ≥10% and a decrease in indexed LV end-diastolic diameter of ≥10% compared to those at baseline was detected in 38% of the patients. There was no significant difference in LGE score between baseline and follow-up (5.8% vs. 7.3%; p=0.38). The change in LGE area (delta-LGE) was significantly lower in patients with LVRR than those without (-0.5%±3.4% vs. 3.0±7.4%; p=0.02). On the other hand, T2 ratio during the follow-up significantly reduced (1.95±0.48 vs. 1.67±0.56; plogistic analysis indicated that baseline LGE score [odds ratio; 0.78; 95% confidence interval (CI) 0.66 to 0.90; p<0.01] together with delta-LGE (odds ratio; 0.77; 95% CI 0.61 to 0.92; p=0.01) were independently associated with subsequent LVRR (p<0.01). The temporal change of LGE-CMR score during the clinical course was significantly correlated with following LVRR. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium.

    Science.gov (United States)

    Gaffey, Ann C; Chen, Minna H; Venkataraman, Chantel M; Trubelja, Alen; Rodell, Christopher B; Dinh, Patrick V; Hung, George; MacArthur, John W; Soopan, Renganaden V; Burdick, Jason A; Atluri, Pavan

    2015-11-01

    The clinical translation of cell-based therapies for ischemic heart disease has been limited because of low cell retention (myocardium. To address these issues, we developed an injectable hyaluronic acid (HA) shear-thinning hydrogel (STG) and endothelial progenitor cell (EPC) construct (STG-EPC). The STG assembles as a result of interactions of adamantine- and β-cyclodextrin-modified HA. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial border zone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. Endothelial progenitor cells (DiLDL(+) VEGFR2(+) CD34(+)) were harvested from adult male rats, cultured, and suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. The STG-EPC constructs were injected at the border zone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the enhanced green fluorescent proteins from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (phosphate buffered saline injection); intramyocardial injection of EPCs alone; injection of the STG alone; and treatment with the STG-EPC construct. Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. Endothelial progenitor cells demonstrated viability within the STG. A marked increase in EPC engraftment was observed 1-week postinjection within the treated myocardium with gel delivery, compared with EPC injection alone (17.2 ± 0.8 cells per high power field (HPF) vs 3.5 cells ± 1.3 cells per HPF, P = .0002). A

  10. Injectable shear-thinning hydrogels to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium

    Science.gov (United States)

    Gaffey, Ann C.; Chen, Minna H.; Venkataraman, Chantel M.; Trubelja, Alen; Rodell, Christopher B.; Dinh, Patrick V.; Hung, George; MacArthur, John W.; Soopan, Renganaden V.; Burdick, Jason A.; Atluri, Pavan

    2015-01-01

    OBJECTIVES The clinical translation of cell based therapies for ischemic heart disease has been limited due to low cell retention (myocardial borderzone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS EPCs (DiLDL+ VEGFR2+ CD34+) were harvested from adult male Wistar Rats, cultured, and then suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. STG-EPC constructs were injected at the borderzone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the eGFP+ EPCs from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (PBS injection), intramyocardial injection of EPCs alone (EPC), injection of the STG alone (STG), and treatment with the gel-EPC construct (STG-EPC). Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS EPCs demonstrated viability within the STG. A marked increase in EPC engraftment was observed one-week post-injection within the treated myocardium with gel delivery when compared to EPC injection alone (17.2 ± 0.8 cells/HPF vs. 3.5 cells ± 1.3 cells/HPF, p = 0.0002). A statistically significant increase in vasculogenesis was noted with the STG-EPC construct (15.3 ± 5.8 vessels/HPF) when compared to control (p treatment compared to the control. CONCLUSIONS A novel injectable shear-thinning hyaluronic acid hydrogel seeded with EPCs enhanced cell retention and vasculogenesis after delivery to ischemic myocardium. This therapy limited adverse myocardial remodeling while preserving contractility. PMID:26293548

  11. Can Native T1 Mapping Differentiate between Healthy and Diffuse Diseased Myocardium in Clinical Routine Cardiac MR Imaging?

    Science.gov (United States)

    Goebel, Juliane; Seifert, Ingmar; Nensa, Felix; Schemuth, Haemi P; Maderwald, Stefan; Quick, Harald H; Schlosser, Thomas; Jensen, Christoph; Bruder, Oliver; Nassenstein, Kai

    2016-01-01

    T1 mapping allows quantitative myocardial assessment, but its value in clinical routine remains unclear. We investigated, whether the average native myocardial T1 value can be used as a diagnostic classifier between healthy and diffuse diseased myocardium. Native T1 mapping was performed in 54 persons with healthy hearts and in 150 patients with diffuse myocardial pathologies (coronary artery disease (CAD): n = 76, acute myocarditis: n = 19, convalescent myocarditis: n = 26, hypertrophic cardiomyopathy (HCM): n = 12, dilated cardiomyopathy (DCM): n = 17) at 1.5 Tesla in a mid-ventricular short axis slice using a modified Look-Locker inversion recovery (MOLLI) sequence. The average native myocardial T1 value was measured using dedicated software for each patient. The mean as well as the range of the observed average T1 values were calculated for each group, and compared using t-test. The ability of T1 mapping to differentiate between healthy and diffuse diseased myocardium was assessed using receiver operating characteristic analysis (ROC). The mean T1 value of the group "healthy hearts" (955±34ms) differed significantly from that of the groups DCM (992±37ms, pmyocarditis (974±36ms, p = 0.044). No significant difference was observed between the groups "healthy hearts" and CAD (951±37ms, p = 0.453) or convalescent myocarditis (965±40ms, p = 0.240). The average native T1 value varied considerably within all groups (range: healthy hearts, 838-1018ms; DCM, 882-1034ms; HCM, 897-1043ms; acute myocarditis, 925-1025ms; CAD, 867-1082ms; convalescent myocarditis, 890-1071ms) and overlapped broadly between all groups. ROC analysis showed, that the average native T1 value does not allow for differentiating between healthy and diffuse diseased myocardium, except for the subgroup of DCM. The average native T1 value in cardiac MR imaging does not allow differentiating between healthy and diffusely diseased myocardium in individual cases.

  12. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Trupti Sarda

    2016-01-01

    Full Text Available Background: Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. Aim: This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM. Materials and Methods: A total of 45 patients affected with Type 2 diabetes mellitus were recruited and divided into three groups with 15 patients each according to their periodontal status: Group I consisting of healthy individuals, Group II consisting of chronic gingivitis, and Group III consisting of chronic generalized severe periodontitis. They were assessed clinically, biochemically, and echocardiographically. LVM was calculated according to Devereux formula and was indexed to height. Results: The differences in the means for LVM and LVM index (LVMI were statistically significant in three groups with a P = 0.006 and 0.014, respectively. After adjusting for the confounders, the mean values of LVM in Group I, II, and III were 149.35 ± 35.51 g, 147.95 ± 31.59 g, and 156.36 ± 36.57 g, respectively and for LVMI, the mean values were 43.61 ± 12.16 g/m 2.7 (Group I, 47.12 ± 10.84 g/m 2.7 (Group II, and 46.34 ± 12.55 g/m 2.7 (Group III. Conclusions: A positive association between chronic generalized severe periodontitis and increased LVM in Type 2 DM patients was observed, suggesting the role of periodontal disease in the left ventricular hypertrophy.

  13. Expression of periodontal inflammation into left ventricular hypertrophy in Type 2 diabetes mellitus: A cross-sectional study.

    Science.gov (United States)

    Sarda, Trupti; Rathod, Surekha; Kolte, Abhay; Bodhare, Girish; Modak, Anil

    2016-01-01

    Chronic periodontitis, an inflammatory disease, is closely related to certain systemic conditions such as cardiovascular diseases, obesity, and Type 2 diabetes mellitus. These conditions, occurring as comorbidities, synergically affect periodontal tissues. This study aims to examine whether chronic gingivitis and chronic generalized severe periodontitis in patients with Type 2 diabetes mellitus are associated with increased left ventricular mass (LVM). A total of 45 patients affected with Type 2 diabetes mellitus were recruited and divided into three groups with 15 patients each according to their periodontal status: Group I consisting of healthy individuals, Group II consisting of chronic gingivitis, and Group III consisting of chronic generalized severe periodontitis. They were assessed clinically, biochemically, and echocardiographically. LVM was calculated according to Devereux formula and was indexed to height. The differences in the means for LVM and LVM index (LVMI) were statistically significant in three groups with a P = 0.006 and 0.014, respectively. After adjusting for the confounders, the mean values of LVM in Group I, II, and III were 149.35 ± 35.51 g, 147.95 ± 31.59 g, and 156.36 ± 36.57 g, respectively and for LVMI, the mean values were 43.61 ± 12.16 g/m(2.7) (Group I), 47.12 ± 10.84 g/m(2.7) (Group II), and 46.34 ± 12.55 g/m(2.7) (Group III). A positive association between chronic generalized severe periodontitis and increased LVM in Type 2 DM patients was observed, suggesting the role of periodontal disease in the left ventricular hypertrophy.

  14. Detection of left ventricular thrombi by echotomography and computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kanemitsu, H.; Hirata, S.; Inagaki, T.; Ishikawa, K. (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

    1981-09-01

    Left ventricular (LV) thrombi are rarely recognized during life, though they are not infrequent at the post-mortem examination of patients succumbed to valvular disease, acute myocardial infarction, and cardiomyopathy. We presented five cases in which LV thrombi were detected by cross-sectional echocardiography (CSE) and confirmed by computed tomography. The main purpose of this study was to compare the echocardiographic findings of the LV thrombi with the manifestations of the LV thrombi on the computed tomograms, with a hope to augment the clinical utility of CSE in the detection of LV thrombi. CSE was recorded from the apical and four-chamber views in addition to the conventional approach. A computed tomographic whole-body scanner which utilized a continuously rotating gantry and pulsed anode with X-ray radiation collimated to form a thin fan-shaped beam was used. A complete section scan was performed in 3 seconds. Sustained enhancement was obtained with a rapid intravenous infusion of 30% meglumine iothalanate. Most of the LV thrombi showed an abnormal echo with irregular borders and/or a mobile mass echo at the apex by CSE. Computed tomographic findings suggestive of LV thrombi appeared as a defect, which was apparently different in quality from the surrounding myocardium or valvular apparatus. These findings were quite consistent with those of CSE with respect to the number and the location of the LV thrombi.

  15. Study on the effects of six intravenous anesthetic agents on regional ventricular function in dogs (thiopental, etomidate, propofol, fentanyl, sufentanil, alfentanil)

    NARCIS (Netherlands)

    de Hert, S. G.

    1991-01-01

    This study evaluates the effects of 30 min increasing doses infusions of six intravenous anesthetic agents (thiopental, etomidate, propofol, fentanyl, sufentanil and alfentanil) on regional ventricular function in a normal and an acute ischemic heart segment in dogs. Part 1 discusses the methodology

  16. Atrial fibrillation is an independent risk factor for ventricular fibrillation: a large-scale population-based case-control study

    NARCIS (Netherlands)

    Bardai, Abdennasser; Blom, Marieke T.; van Hoeijen, Daniel A.; van Deutekom, Hanneke W. M.; Brouwer, Henk J.; Tan, Hanno L.

    2014-01-01

    Atrial fibrillation (AF) is associated with sudden cardiac death. We aimed to study whether AF is associated with ventricular fibrillation (VF), the most common cause of sudden cardiac death and whether this association is independent of confounders, ie, concomitant disease, use of antiarrhythmic or

  17. Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tract

    NARCIS (Netherlands)

    Rana, M. Sameer; Horsten, Noortje C. A.; Tesink-Taekema, Sabina; Lamers, Wout H.; Moorman, Antoon F. M.; van den Hoff, Maurice J. B.

    2007-01-01

    Recent molecular lineage analyses in mouse have demonstrated that the right ventricle is recruited from anterior mesoderm in later stages of cardiac development. This is in contrast to current views of development in the chicken heart, which suggest that the initial heart tube contains a subset of

  18. Late ventricular potentials in risk assessment of the occurrence of complex ventricular arrhythmia in patients with myocardial infarction and heart failure

    Directory of Open Access Journals (Sweden)

    Ćosić Zoran

    2004-01-01

    Full Text Available Aim. To determine the prognostic significance of late ventricular potentials on signal-averaged electrocardiogram and left ventricular ejection fraction for the occurrence of complex ventricular arrhythmia in patients treated with accelerated tissue-type plasminogen activator, using the rapid protocol, within six months of acute myocardial infarction. Methods. In this analytic observational prospective study patients were divided into four groups: patients with left ventricular ejection fraction bellow 40% and late ventricular potentials, patients with left ventricular ejection fraction bellow 40% and without late ventricular potentials, patients with left ventricular ejection fraction over 40% and late ventricular potentials, and patients with left ventricular ejection fraction over 40% and without late ventricular potentials. Complex ventricular arrhythmias (Lown grade IVa, IVb, and V were recorded using standard electrocardiography and 24-hour Holter monitoring 21, 60, and 90 days after acute myocardial infarction, respectively. Serial recordings of signal-averaged electrocardiogram were obtained 30, 90, and 180 days after acute myocardial infarction. Left ventricular ejection fraction was determined by echocardiography between 15 and 21 days after acute myocardial infarction. Multivariant logistic regression analysis was used to evaluate the relation between late ventricular potentials and left ventricular ejection fraction with the occurrence of complex ventricular arrhythmias. Sensitivity, specificity, positive and negative predictive values of late ventricular potentials and left ventricular ejection fraction for the occurrence of complex ventricular arrhythmias were determined. Results. The prospective study included 80 patients (73% men, mean age 64 ± 3.5 years. Complex ventricular arrhythmias were recorded in 34 (42.5% of patients, all 17 (50% of which were from the first group (p<0.01. Complex ventricular arrhythmias were recorded in

  19. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    Science.gov (United States)

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  20. Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach.

    Science.gov (United States)

    Kuster, Diederik W D; Merkus, Daphne; Kremer, Andreas; van Ijcken, Wilfred F J; de Beer, Vincent J; Verhoeven, Adrie J M; Duncker, Dirk J

    2011-11-01

    Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR two-fold (p two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling.

  1. Multiple cavities in myocardium of left ventricle after irradiation therapy for breast cancer. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Shinobu; Kato, Hiroshi; Koizumi, Katsumi [Nishi-Kobe Medical Center (Japan)] (and others)

    1999-09-01

    A 68-year-old woman was admitted to our hospital with congestive heart failure. She had been diagnosed with hypertrophic cardiomyopathy 12 years ago in another hospital. She had received irradiation therapy for left breast cancer 33 years ago after resection of her left breast. Echocardiography revealed left ventricular hypertrophy and wall motion hypokinesis, and multiple cavities in the myocardium of the left ventricle, interventricular septum, and anterior wall. Some cavities were observed to connect to the left ventricular cavity and Doppler echocardiography showed slow velocity flows in them different from that of the coronary artery. The pathologic diagnosis was severe sclerosis of the left coronary artery, especially the left descending artery and its branch, which was the area with irradiation. Histopathology revealed sclerotic changes of the coronary artery causing acute and chronic myocardial infarction, and incomplete regeneration and hypertrophy of cardiac cells. There was no sign of hypertrophic cardiomyopathy. Myocardial degeneration and deciduation were present next to the cavities connected to left ventricle-like fistulas. (author)

  2. Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium

    Directory of Open Access Journals (Sweden)

    Henk Granzier

    2010-01-01

    Full Text Available Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA that expresses mainly N2BA titin, and the bovine left ventricle (BLV that expresses a mixture of both N2B and N2BA isforms. For comparison we also studied mouse left ventricular (MLV myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a “viscous break” that is on during diastole and off during systole.

  3. Accumulation of nonesterified fatty acids in the dog myocardium during coronary artery occlusion determined by a method using 9-anthryldiazomethane.

    Science.gov (United States)

    Miura, I; Hashizume, H; Akutsu, H; Hara, Y; Abiko, Y

    1987-01-01

    The levels of nonesterified fatty acids (NEFA) in the myocardium during ischemia were determined by a simple method, which requires neither previous separation with thin-layer chromatography nor heating. After being extracted with Folch's solution, NEFA were subjected to fluorescent labeling with 9-anthryldiazomethane at room temperature, separation with high-pressure liquid chromatography, and then detection by a flow-through fluorometer. Calibration and validation studies revealed that this method was satisfactory. The left anterior descending coronary artery was completely occluded for 90 min in dogs anesthetized with pentobarbital. In the nonischemic myocardium, the levels of lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, and arachidonic acids were 5.31, 15.85, 47.06, 2.59, 23.92, 37.90, 38.69, and 3.99 nmol/g wet tissue, respectively, and those in the ischemic myocardium 5.67, 22.16, 75.94, 6.65, 42.67, 61.75, 70.06, and 13.39 nmol/g wet tissue, respectively, the total NEFA in the former being 175.3 and that in the latter 298.3 nmol/g wet tissue. The increase in myocardial NEFA during ischemia was significant except for lauric and myristic acids, and the increase in arachidonic acid was the greatest. The ratio of the level of arachidonic acid in the ischemic myocardium to that in the nonischemic myocardium was 335.6%.

  4. [Not isolated ventricular compaction in an infant].

    Science.gov (United States)

    Dibi, A; Jabourik, F; Bentahila, A

    2016-04-01

    Not isolated ventricular compaction cardiomyopathy is a rare deasese described both in children than in adults. It due to the interruption of the embryogenic compaction process of the normal myocardium. We report a pediatric observation of noncompaction of the left ventricle. This is a 4-month girl who was admitted to an array of heart failure with systolic murmur to FM. Chest radiography showed cardiomegaly. The ECG showed repolarization disorder. The echocardiography objectified dilated left cavities with thickened wall and anechoic areas (sinusoidal), a mitral regurgitation GII and minimal tricuspid regurgitation. NCVI is a rare cause of heart failure in infants. The management is based on guidelines for various clinical symptomatology. Its discovery in children should lead to screening of first-degree relative. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study

    DEFF Research Database (Denmark)

    Larstorp, A C K; Okin, P M; Devereux, R B

    2011-01-01

    The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320...

  6. A novel myocardium segmentation approach based on neutrosophic active contour model.

    Science.gov (United States)

    Guo, Yanhui; Du, Guo-Qing; Xue, Jing-Yi; Xia, Rong; Wang, Yu-Hang

    2017-04-01

    Automatic delineation of the myocardium in echocardiography can assist radiologists to diagnosis heart problems. However, it is still challenging to distinguish myocardium from other tissue due to a low signal-to-noise ratio, low contrast, vague boundary, and speckle noise. The purpose of this study is to automatically detect myocardium region in left ventricle myocardial contrast echocardiography (LVMCE) images to help radiologists' diagnosis and further measurement on infarction size. The LVMCE image is firstly mapped into neutrosophic similarity (NS) domain using the intensity and homogeneity features. Then, a neutrosophic active contour model (NACM) is proposed and the energy function is defined by the NS values. Finally, the ventricle is detected using the curve evolving results. The ventricle's boundary is identified as the endocardium. To speed up the evolution procedure and increase the detection accuracy, a clustering algorithm is employed to obtain the initial ventricle region. The curve evolution procedure in NACM is utilized again to obtain the epicardium, where the initial contour uses the detected endocardium and the anatomy knowledge on the thickness of the myocardium. Echocardiographic studies are performed on 10 male Sprague-Dawley rats using a Vivid 7 system including 5 normal cases and 5 rats with myocardial infarction. The myocardium boundaries manually outlined by an experienced radiologist are used as the reference standard for the performance evaluation. Two metrics, Hdist and AvgDist, are employed to evaluate the detection results. The NACM method was compared with those from the eliminated particle swarm optimization (EPSO) and active contour model without edges (ACMWE) methods. The mean and standard deviation of the Hdist and AvgDist on endocardium are 6.83 ± 1.12mm and 0.79 ± 0.28mm using EPSO method, 7.12 ± 0.98mm and 0.82 ± 0.32mm using ACMWE method, and 4.55 ± 0.9mm and 0.58 ± 0.18mm using NACM method, respectively. The

  7. Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Pilichou, Kalliopi; Remme, Carol Ann; Basso, Cristina; Campian, Maria E; Rizzo, Stefania; Barnett, Phil; Scicluna, Brendon P; Bauce, Barbara; van den Hoff, Maurice J B; de Bakker, Jacques M T; Tan, Hanno L; Valente, Marialuisa; Nava, Andrea; Wilde, Arthur A M; Moorman, Antoon F M; Thiene, Gaetano; Bezzina, Connie R

    2009-08-03

    Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.

  8. [The cholinergic non-excitability phenomenon in the atrial myocardium of lower vertebrates].

    Science.gov (United States)

    Abramochkin, D V; Kuz'min, V S; Sukhova, G S; Rozenshtraukh, L V

    2009-06-01

    Changes of electric activity induced by acetylcholine were studied in atrial myocardium of fishes (cod and carp) and reptilians (lizard and grass-snake). Standart microelectrode technique and novel method of optical mapping were used in the study. Acetylcholine (1-50 microM) provoked decrease of the action potential amplitude down to full inhibition of electrical activity in wide regions of atrium of cod and carp. We define this phenomenon as cholinergic inexcitability. In other regions excitation persisted even during action of 500 microM acetylcholine. In atria of lizard and grass-snake acetylcholine caused shortening of action potential without changes in it's amplitude. Local cholinergic inexcitability, shown in the atrial myocardium of fishes, is quite similar to the phenomenon, that was described earlier in the atria of frogs. It presents the heart of fish as an interesting model for study of mechanisms of cholinergic atrial arrhythmias initiation.

  9. Catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation (CASTLE-AF) - study design.

    Science.gov (United States)

    Marrouche, Nassir F; Brachmann, Johannes

    2009-08-01

    Electrical isolation of the pulmonary veins by catheter ablation is an emerging treatment modality for the treatment of atrial fibrillation (AF) and is increasingly used in patients with heart failure. The catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation trial (CASTLE-AF) is a rand