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Sample records for ventricular myocyte hypertrophy

  1. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy

    Science.gov (United States)

    Yamamoto, Shimako; Yang, Guiping; Zablocki, Daniela; Liu, Jing; Hong, Chull; Kim, Song-Jung; Soler, Sandra; Odashima, Mari; Thaisz, Jill; Yehia, Ghassan; Molina, Carlos A.; Yatani, Atsuko; Vatner, Dorothy E.; Vatner, Stephen F.; Sadoshima, Junichi

    2003-01-01

    Activation of mammalian sterile 20–like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity–dependent manner. In vivo, cardiac-specific overexpression of Mst1 in transgenic mice results in activation of caspases, increased apoptosis, and dilated cardiomyopathy. Surprisingly, however, Mst1 prevents compensatory cardiac myocyte elongation or hypertrophy despite increased wall stress, thereby obscuring the use of the Frank-Starling mechanism, a fundamental mechanism by which the heart maintains cardiac output in response to increased mechanical load at the single myocyte level. Furthermore, Mst1 is activated by ischemia/reperfusion in the mouse heart in vivo. Suppression of endogenous Mst1 by cardiac-specific overexpression of dominant-negative Mst1 in transgenic mice prevents myocyte death by pathologic insults. These results show that Mst1 works as both an essential initiator of apoptosis and an inhibitor of hypertrophy in cardiac myocytes, resulting in a previously unrecognized form of cardiomyopathy. PMID:12750396

  2. Impaired beta-adrenergic response and decreased L-type calcium current of hypertrophied left ventricular myocytes in postinfarction heart failure

    Scientific Electronic Library Online (English)

    R.M., Saraiva; N.G.B., Chedid; C.C., Quintero H.; L.E., Díaz G.; M.O., Masuda.

    2003-05-01

    Full Text Available Infarct-induced heart failure is usually associated with cardiac hypertrophy and decreased ß-adrenergic responsiveness. However, conflicting results have been reported concerning the density of L-type calcium current (I Ca(L)), and the mechanisms underlying the decreased ß-adrenergic inotropic respo [...] nse. We determined I Ca(L) density, cytoplasmic calcium ([Ca2+]i) transients, and the effects of ß-adrenergic stimulation (isoproterenol) in a model of postinfarction heart failure in rats. Left ventricular myocytes were obtained by enzymatic digestion 8-10 weeks after infarction. Electrophysiological recordings were obtained using the patch-clamp technique. [Ca2+]i transients were investigated via fura-2 fluorescence. ß-Adrenergic receptor density was determined by [³H]-dihydroalprenolol binding to left ventricle homogenates. Postinfarction myocytes showed a significant 25% reduction in mean I Ca(L) density (5.7 ± 0.28 vs 7.6 ± 0.32 pA/pF) and a 19% reduction in mean peak [Ca2+]i transients (0.13 ± 0.007 vs 0.16 ± 0.009) compared to sham myocytes. The isoproterenol-stimulated increase in I Ca(L) was significantly smaller in postinfarction myocytes (Emax: 63.6 ± 4.3 vs 123.3 ± 0.9% in sham myocytes), but EC50 was not altered. The isoproterenol-stimulated peak amplitude of [Ca2+]i transients was also blunted in postinfarction myocytes. Adenylate cyclase activation through forskolin produced similar I Ca(L) increases in both groups. ß-Adrenergic receptor density was significantly reduced in homogenates from infarcted hearts (Bmax: 93.89 ± 20.22 vs 271.5 ± 31.43 fmol/mg protein in sham myocytes), while Kd values were similar. We conclude that postinfarction myocytes from large infarcts display reduced I Ca(L) density and peak [Ca2+]i transients. The response to ß-adrenergic stimulation was also reduced and was probably related to ß-adrenergic receptor down-regulation and not to changes in adenylate cyclase activity.

  3. Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

    Science.gov (United States)

    Corda, S; Mebazaa, A; Gandolfini, M P; Fitting, C; Marotte, F; Peynet, J; Charlemagne, D; Cavaillon, J M; Payen, D; Rappaport, L; Samuel, J L

    1997-11-01

    Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy. PMID:9351441

  4. Automated microscopy of cardiac myocyte hypertrophy: a case study on the role of intracellular ?-adrenergic receptors.

    Science.gov (United States)

    Ryall, Karen A; Saucerman, Jeffrey J

    2015-01-01

    Traditional approaches for measuring cardiac myocyte hypertrophy have been of low throughput and subjective, limiting the scope of experimental studies designed to understand it. Here, we describe an automated image acquisition and analysis platform for studying the dynamics of cardiac myocyte hypertrophy in vitro. Image acquisition scripts record 5?×?5 mosaic images of fluorescent protein-labeled neonatal rat ventricular myocytes from each well of a 96-well plate using the microscope's automated stage and focus. Image analysis algorithms automatically segment myocyte boundaries, track myocytes, and quantify changes in shape. We describe each step of the image acquisition and analysis algorithms and provide specific examples of how to implement them using Metamorph and CellProfiler software. With this system, shape dynamics of thousands of individual cardiac myocytes can be tracked for up to a week. This imaging platform was recently applied to study reversal of cardiac myocyte hypertrophy following withdrawal of the ?-adrenergic agonist phenylephrine. Hypertrophy readily reversed at low but not high levels of ?-adrenergic signaling, leading to identification of an intracellular population of ?-adrenergic receptors responsible for this reversibility delay. PMID:25304353

  5. Increased sarcolemmal Na(+)/H(+) exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block.

    Science.gov (United States)

    van Borren, Marcel M G J; Vos, Marc A; Houtman, Marien J C; Antoons, Gudrun; Ravesloot, Jan H

    2013-01-01

    Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na(+) influx in hypertrophied cAVB ventricular myocytes contribute to these lethal arrhythmias. The increased Na(+) influx was not mediated by Na(+) channels, in fact the Na(+) current proved reduced in cAVB myocytes. Here we tested the hypothesis that increased activity of the Na(+)/H(+) exchanger type 1 (NHE-1), commonly observed in hypertrophic hearts, causes the elevated Na(+) influx. Cardiac acid-base transport was studied with a pH-sensitive fluorescent dye in ventricular myocytes isolated from control and hypertrophied cAVB hearts; the H(+) equivalent flux through NHE-1, Na(+)-HCO(-) 3 cotransport (NBC), Cl(-)/OH(-) exchange (CHE), and Cl(-)/HCO(-) 3 exchange (AE) were determined and normalized per liter cell water and corrected for surface-to-volume ratio. In cAVB, sarcolemmal NHE-1 flux was increased by 65 ± 6.3% in the pH i interval 6.3-7.2 and NBC, AE, and CHE fluxes remained unchanged. Accordingly, at steady-state intracellular pH the total sarcolemmal Na(+) influx by NHE-1 + NBC increased from 8.5 ± 1.5 amol/?m(2)/min in normal myocytes to 15 ± 2.4 amol/?m(2)/min in hypertrophied cAVB myocytes. We conclude that compensated cardiac hypertrophy in cAVB dogs is accompanied with an increased sarcolemmal NHE-1 activity. This in conjunction with unchanged activity of the other acid-base transporters will raise the intracellular Na(+) in hypertrophied cAVB myocytes. PMID:24324438

  6. Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

    Directory of Open Access Journals (Sweden)

    JanHindrikRavesloot

    2013-11-01

    Full Text Available Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB, are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes contribute to these lethal arrhythmias. The increased Na+ influx was not mediated by Na+ channels, in fact the Na+ current proved reduced in cAVB myocytes. Here we tested the hypothesis that increased activity of the Na+/H+ exchanger type 1 (NHE-1, commonly observed in hypertrophic hearts, causes the elevated Na+ influx. Cardiac acid-base transport was studied with a pH-sensitive fluorescent dye in ventricular myocytes isolated from control and hypertrophied cAVB hearts; the H+ equivalent flux through NHE-1, Na+-HCO3- cotransport (NBC, Cl-/OH- exchange (CHE and Cl-/HCO3- exchange (AE were determined and normalized per liter cell water and corrected for surface-to-volume ratio. In cAVB, sarcolemmal NHE-1 flux was increased by 65±6.3% in the pHi interval 6.3-7.2 and NBC, AE and CHE fluxes remained unchanged. Accordingly, at steady-state intracellular pH the total sarcolemmal Na+ influx by NHE-1+NBC increased from 8.5±1.5 amol/?m2/min in normal myocytes to 15±2.4 amol/?m2/min in hypertrophied cAVB myocytes. We conclude that compensated cardiac hypertrophy in cAVB dogs is accompanied with an increased sarcolemmal NHE-1 activity. This in conjunction with unchanged activity of the other acid-base transporters will raise the intracellular Na+ in hypertrophied cAVB myocytes.

  7. Estrogen exerts concentration-dependent pro-and anti-hypertrophic effects on adult cultured ventricular myocytes. Role of NHE-1 in estrogen-induced hypertrophy.

    Science.gov (United States)

    Kili?, Ana; Javadov, Sabzali; Karmazyn, Morris

    2009-03-01

    Estrogen has been shown to protect the heart and attenuate myocardial hypertrophy and left ventricular remodelling through as yet to be defined mechanisms. In the present study we examined concentration-dependent effects of estrogen on hypertrophy of adult rat cardiomyocytes, potential underlying mechanisms related to intracellular pH (pHi) and possible sex-dependent responses. Cardiomyocytes were isolated from adult male and female Sprague-Dawley rats and used immediately for pHi determinations or cultured and subsequently treated for 24 h with 17beta-estradiol to assess hypertrophic responses. Fluorometric measurements with the pHi-sensitive dye BCECF demonstrated that at 1 pM 17beta-estradiol increased pHi (+0.05 pH units in females and +0.12 pH units in males, P<0.05) by a rapid non-genomic mechanism that was blocked by the sodium-hydrogen exchange isoform 1 (NHE-1) specific inhibitor AVE-4890 (AVE, 5 microM). Treatment with 1 pM 17beta-estradiol for 24 h increased cell size (females: 20%, P<0.05; males: 29%, P<0.05) and ANP expression (females: 414%, P<0.05; males: 497%, P<0.05) in a NHE-1-, and ERK1/2 MAPK-dependent manner. At 1 nM, 17beta-estradiol decreased pHi (females: -0.24 pH units, P<0.05; males: -0.07 pH units, P<0.05) which was also prevented by AVE, although at this concentration the hormone had no direct hypertrophic effect but instead prevented hypertrophy induced by phenylephrine. Our results show that low levels of estrogen produce cardiomyocyte hypertrophy through ERK/NHE-1 activation and intracellular alkalinization whereas an antihypertrophic effect is seen at high concentrations. These effects may further our understanding of the role of estrogen in heart disease particularly associated with hypertrophy. PMID:19111554

  8. Anchored p90 Ribosomal S6 Kinase 3 is Required for Cardiac Myocyte Hypertrophy

    Science.gov (United States)

    Li, Jinliang; Kritzer, Michael D.; Carlisle Michel, Jennifer J.; Le, Andrew; Thakur, Hrishikesh; Gayanilo, Marjorie; Passariello, Catherine; Negro, Alejandra; Danial, Joshua B.; Oskouei, Behzad; Sanders, Michael; Hare, Joshua M.; Hanauer, Andre; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2012-01-01

    Rationale Cardiac myocyte hypertrophy is the main compensatory response to chronic stress on the heart. p90 Ribosomal S6 Kinase (RSK) family members are effectors for extracellular signal-regulated kinases that induce myocyte growth. Although increased RSK activity has been observed in stressed myocytes, the functions of individual RSK family members have remained poorly defined, despite being potential therapeutic targets for cardiac disease. Objective To demonstrate that type 3 RSK (RSK3) is required for cardiac myocyte hypertrophy. Methods and Results RSK3 contains a unique N-terminal domain that is not conserved in other RSK family members. We show that this domain mediates the regulated binding of RSK3 to the muscle A-kinase anchoring protein (mAKAP) scaffold, defining a novel kinase anchoring event. Disruption of both RSK3 expression using RNA interference and RSK3 anchoring using a competing mAKAP peptide inhibited the hypertrophy of cultured myocytes. In vivo, RSK3 gene deletion in the mouse attenuated the concentric myocyte hypertrophy induced by pressure overload and catecholamine infusion. Conclusions Taken together, these data demonstrate that anchored RSK3 transduces signals that modulate pathologic myocyte growth. Targeting of signaling complexes that contain select kinase isoforms should provide an approach for the specific inhibition of cardiac myocyte hypertrophy and for the development of novel strategies for the prevention and treatment of heart failure. PMID:22997248

  9. Automated imaging reveals a concentration dependent delay in reversibility of cardiac myocyte hypertrophy

    OpenAIRE

    Ryall, Karen A.; Saucerman, Jeffrey J.

    2012-01-01

    Cardiac hypertrophy is controlled by a dense signaling network with many pathways associated with cardiac myocyte growth. New large scale methodology is required to quantitatively characterize the pathways that distinguish reversible forms of hypertrophy from irreversible forms that lead to heart failure. Our automated image acquisition method records 5×5 mosaic images of fluorescent protein-labeled cardiac myocytes within each well of a 96-well plate using an automated stage and focus. Post...

  10. Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure

    Science.gov (United States)

    Ding, B.; Price, R. L.; Goldsmith, E. C.; Borg, T. K.; Yan, X.; Douglas, P. S.; Weinberg, E. O.; Bartunek, J.; Thielen, T.; Didenko, V. V.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, Pstaining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

  11. Echocardiographic left ventricular hypertrophy in Chinese endurance athletes.

    OpenAIRE

    Lo, Y. S.; Chin, M K

    1990-01-01

    Most echocardiographic data on the athletic heart syndrome originate from the United States and Western Europe. There are no published data on echocardiographically documented left ventricular hypertrophy in Asian athletes. We investigated the echocardiographic changes which take place with endurance training by studying eight Hong Kong national cyclists. This study confirms that left ventricular hypertrophy and increased left ventricular end-diastolic dimensions are common findings in Chines...

  12. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-trong Minh; Williams, George S. B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  13. Two types of calcium channels in guinea pig ventricular myocytes.

    OpenAIRE

    Mitra, R.; Morad, M.

    1986-01-01

    In cardiac muscle, Ca2+ plays a key role in regulation of numerous processes, including generation of the action potential and development of tension. The entry of Ca2+ into the cell is regulated primarily by voltage-gated channels in the membrane. Until recently, it was felt that only one type of Ca2+ channel existed in cardiac ventricular muscle. Experiments reported here suggest that in isolated guinea pig ventricular myocytes, there are two distinct types of Ca2+ channels with markedly di...

  14. Two Types of Calcium Channels in Guinea Pig Ventricular Myocytes

    Science.gov (United States)

    Mitra, Raman; Morad, Martin

    1986-07-01

    In cardiac muscle, Ca2+ plays a key role in regulation of numerous processes, including generation of the action potential and development of tension. The entry of Ca2+ into the cell is regulated primarily by voltage-gated channels in the membrane. Until recently, it was felt that only one type of Ca2+ channel existed in cardiac ventricular muscle. Experiments reported here suggest that in isolated guinea pig ventricular myocytes, there are two distinct types of Ca2+ channels with markedly different activation thresholds, inactivation kinetics, and sensitivities to inorganic and organic Ca2+ channel blockers. The channels were also distinguished based on their response to increased frequency of clamping such that the current through the low-threshold channel decreased while that through the high-threshold channel increased. In a few cells, the current through both channels was enhanced by isoproterenol, a ? -adrenergic agonist, but only the high-threshold channel was enhanced by the Ca2+-channel agonist Bay K 8644. Thus, isolated guinea pig ventricular myocytes appear to have two types of Ca2+ channels distinguished by various criteria.

  15. Mechanisms of Ca2+ Handling in Zebrafish Ventricular Myocytes

    OpenAIRE

    Bovo, Elisa; Dvornikov, Alexey V.; Mazurek, Stefan R.; Tombe, Pieter P.; Zima, Aleksey V.

    2013-01-01

    Zebrafish serves as a promising transgenic animal model that can be used to study cardiac Ca2+ regulation. However, mechanisms of sarcoplasmic reticulum (SR) Ca2+ handling in zebrafish heart have not been systematically explored. We found that in zebrafish ventricular myocytes the action potential (AP)-induced Ca2+ transient is mainly (80%) mediated by Ca2+ influx via L-type Ca2+ channels (LTCC) and only 20% by Ca2+ released from the SR. This small contribution of the SR to the Ca2+ transient...

  16. An Updated Concept for Left Ventricular Hypertrophy Risk in Hypertension

    OpenAIRE

    Frohlich, Edward D.

    2009-01-01

    Left ventricular hypertrophy (LVH) was one of the first three “factors of risk” originally identified by the Framingham Heart Study predisposing the patient to premature morbidity and mortality resulting from coronary heart disease. Among the initial approaches toward specific risk reduction were antihypertensive agents that reduce left ventricular (LV) mass with control of arterial pressure. However, the indication to reduce risk from LVH has not been approved by the federal regulatory a...

  17. Nifedipine inhibits cardiac hypertrophy and left ventricular dysfunction in response to pressure overload.

    Science.gov (United States)

    Ago, Tetsuro; Yang, Yanfei; Zhai, Peiyong; Sadoshima, Junichi

    2010-08-01

    Pathological hypertrophy is commonly induced by activation of protein kinases phosphorylating class II histone deacetylases (HDACs) and desuppression of transcription factors, such as nuclear factor of activated T cell (NFAT). We hypothesized that nifedipine, an L-type Ca(2+) channel blocker, inhibits Ca(2+) calmodulin-dependent kinase II (CaMKII) and NFAT, thereby inhibiting pathological hypertrophy. Mice were subjected to sham operation or transverse aortic constriction (TAC) for 2 weeks with or without nifedipine (10 mg/kg/day). Nifedipine did not significantly alter blood pressure or the pressure gradient across the TAC. Nifedipine significantly suppressed TAC-induced increases in left ventricular (LV) weight/body weight (BW; 5.09 +/- 0.80 vs. 4.16 +/- 0.29 mg/g, TAC without and with nifedipine, n = 6,6, p < 0.05), myocyte cross-sectional area (1,681 +/- 285 vs. 1,434 +/- 197 arbitrary units, p < 0.05), and expression of fetal-type genes, including atrial natriuretic factor (35. 9 +/- 6.4 vs. 8.6 +/- 3.3 arbitrary units, p < 0.05). TAC-induced increases in lung weight/BW (7.7 +/- 0.9 vs. 5.5 +/- 0.5 mg/g, p < 0.05) and decreases in LV ejection fraction (65.5 +/- 3.1% vs. 75.7 +/- 3.3%, p < 0.05) were attenuated by nifedipine. Nifedipine caused significant inhibition of TAC-induced activation of NFAT-mediated transcription, which was accompanied by suppression of Thr 286 phosphorylation in CaMKII. Nifedipine inhibited activation of CaMKII and NFAT by phenylephrine, accompanied by suppression of Ser 632 phosphorylation and nuclear exit of HDAC4 in cardiac myocytes. These results suggest that a subpressor dose of nifedipine inhibits pathological hypertrophy in the heart by inhibiting activation of CaMKII and NFAT, a signaling mechanism commonly activated in pathological hypertrophy. PMID:20559781

  18. Hypoxia causes connexin 43 internalization in neonatal rat ventricular myocytes.

    Science.gov (United States)

    Danon, Asaf; Zeevi-Levin, Naama; Pinkovich, Dani Y; Michaeli, Tomer; Berkovich, Alexander; Flugelman, Moshe; Eldar, Yonina C; Rosen, Michael R; Binah, Ofer

    2010-09-01

    Gap junctions produce low resistance pathways between cardiomyocytes and are major determinants of electrical conduction in the heart. Altered distribution and function of connexin 43 (Cx43), the major gap junctional protein in the ventricles, can slow conduction, and thus contribute to arrhythmogenesis in experimental models such as ischemic rat heart and pacing-induced atrial fibrillation. The mechanisms underlying reduced gap junctional density and conductance during ischemia may involve decreased Cx43 synthesis, increased degradation and/or Cx43 migration into areas which do not contribute to intercellular communication. To test more rigorously the hypothesis that hypoxia resulting from ischemia causes Cx43 internalization, we infected neonatal rat ventricular myocytes (NRVM) with a Cx43-GFP chimera, which enabled us to investigate by means of confocal microscopy the effect of hypoxia (1% O2 for 5 h) on Cx43 distribution in live cardiomyocytes. Importantly, this protocol permitted each culture to serve as its own control. To this end we used life confocal microscopy analysis to determine in the same pair of myocytes the effects of hypoxia on Cx43-GFP distribution at the gap junctional (GJ) and non-GJ areas. In support of this hypothesis, we found that compared to normoxia, 5 h of hypoxia reduced the Cx43-GFP signal at the GJ areas (defined as the border area) and caused a corresponding increase in the Cx43-GFP signal at the non-border areas, thus providing an additional explanation for the intercellular uncoupling during ischemic conditions. PMID:20817946

  19. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

    International Nuclear Information System (INIS)

    The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

  20. Highly efficient gene transfer into adult ventricular myocytes by recombinant adenovirus.

    OpenAIRE

    Kirshenbaum, L A; MacLellan, W.R.; Mazur, W; French, B.A.; Schneider, M. D.

    1993-01-01

    Molecular dissection of mechanisms that govern the differentiated cardiac phenotype has, for cogent technical reasons, largely been undertaken to date in neonatal ventricular myocytes. To circumvent expected limitations of other methods, the present study was initiated to determine whether replication-deficient adenovirus would enable efficient gene transfer to adult cardiac cells in culture. Adult rat ventricular myocytes were infected, 24 h after plating, with adenovirus type 5 containing a...

  1. NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

    OpenAIRE

    Rueckschloss, Uwe; Villmow, Marten; Klöckner, Udo

    2010-01-01

    Abstract Since aging increases oxidative stress, we analyzed the contribution of reactive oxygen species (ROS) to the contractile dysfunction of aged ventricular myocytes and investigated whether short-term interference with ROS formation could normalize contractile performance. Isolated ventricular myocytes from young (2-4months) and aged (24-26months) male mice (C57BL/6) were used. We analyzed sarcomere shortening and calcium transients (Indo-1 fluorescence) of voltage...

  2. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    Science.gov (United States)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists. Intercellular contact, communication, and transmission of contractile forces between myocytes appears to play a primary role in remodeling the 2-dimensional cell layer into a parallel alignment of elongated myocytes with highly developed intercalated disk-like junctions. This highly differentiated state is very stable, and cultures which achieve this state exhibit significantly greater longevity than more sparsely plated myocytes. These myocytes typically continue beating, and survive from 6 to more than 12 weeks in culture. When this level of contact and differentiation are not achieved, even among beta-adrenergic stimulated myocytes, contractile activity is not sustained, myofibrils atrophy, there is little or no development of junctional complexes, and the period of myocyte viability is typically no more than 5 weeks in vitro.

  3. Left Ventricular Hypertrophy: Major Risk Factor in Patients with Hypertension: Update and Practical Clinical Applications

    OpenAIRE

    Katholi, Richard E.; Couri, Daniel M.

    2011-01-01

    Left ventricular hypertrophy is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. Since not all patients with hypertension develop left ventricular hypertrophy, there are clinical findings that should be kept in mind that may alert the physician to the presence of left ventricular hypertrophy so a more definitive evaluation can be performed u...

  4. Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovi?, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    2014-01-01

    Ro?. 65, ?. 4 (2014), s. 497-509. ISSN 0867-5910 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.720, year: 2013

  5. Distinct KATP channels mediate the antihypertrophic effects of adenosine receptor activation in neonatal rat ventricular myocytes.

    Science.gov (United States)

    Xia, Ying; Javadov, Sabzali; Gan, Tracey X; Pang, Theresa; Cook, Michael A; Karmazyn, Morris

    2007-01-01

    Recent evidence suggests that both adenosine receptor (AR) and K ATP channel activation exert antihypertrophic effects in cardiac myocytes. We studied the relative contributions of mitochondrial K ATP (mitoK ATP) and sarcolemmal K ATP (sarcK ATP) to the antihypertrophic effects of ARs in primary cultures of neonatal rat ventricular myocytes exposed for 24 h with the alpha1 adrenoceptor agonist phenylephrine (PE). The A1R agonist N6-cyclopentyladenosine (CPA), the A(2A)R agonist CGS21680 [2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine], and the A3R agonist N6-(3-iodobenzyl)adenosine-5'-methyluronamide (IB-MECA) all prevented PE-induced hypertrophy. Glibenclamide, a nonselective K(ATP) channel blocker reversed the antihypertrophic effect of all three AR agonists as determined by cell size and atrial natriuretic peptide expression and early c-fos up-regulation. In contrast, the mitoK(ATP) blocker 5-hydroxydecanoic acid selectively attenuated the effect of CGS21680 and IB-MECA, whereas HMR1098 [1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea, sodium salt], a specific blocker of sarcK(ATP), only abolished the antihypertrophic effect of CPA. Moreover, both CGS21680 and IB-MECA but not CPA decreased the mitochondrial membrane potential when PE was present, similarly to that seen with diazoxide, and both agents inhibited PE-stimulated elevation in mitochondrial Ca2+. All AR agonists diminished PE-induced phosphoserine/threonine kinase and protein kinase B up-regulation, which was unaffected by any K(ATP) blocker. Our data suggest that AR-mediated antihypertrophic effects are mediated by distinct K(ATP) channels, with sarcK(ATP) mediating the antihypertrophic effects of A1R activation, whereas mitoK(ATP) activation mediates the antihypertrophic effects of both A(2A)R and A3R agonists. PMID:17012605

  6. 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 refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.

  7. Docosahexaenoic acid has influence on action potentials and transient outward potassium currents of ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ?-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA on action potentials and Ito. Methods The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique. Results 1. Action potential durations (APDs were prolonged from epicardial to endocardial ventricular myocytes (P 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 ± 15.99 pA/pF, 29.15 ± 5.53 pA/pF, and 12.29 ± 3.62 pA/pF, respectively at +70 mV test potential (P 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 ?mol/L to 100 ?mol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 ?mol/L to 1 ?mol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 ?mol/L to 100 ?mol/L, and its half-inhibited concentration was 5.3 ?mol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations. Conclusion The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

  8. Left Ventricular Hypertrophy Patterns and Incidence of Heart Failure with Preserved versus Reduced Ejection Fraction

    OpenAIRE

    Velagaleti, Raghava S.; Gona, Philimon; Pencina, Michael J.; Aragam, Jayashri; Wang, Thomas J.; Levy, Daniel; D Agostino, Ralph B.; Lee, Douglas S.; Kannel, William B.; Benjamin, Emelia J.; Vasan, Ramachandran S.

    2013-01-01

    Higher left ventricular (LV) mass, wall thickness and internal dimension are associated with increased heart failure (HF) risk. Whether different LV hypertrophy patterns vary with respect to rates and types of HF incidence is unclear. We classified 4768 Framingham Heart Study participants (mean age 50 years; 56% women) into 4 mutually exclusive LV hypertrophy pattern groups (normal, concentric remodeling, concentric hypertrophy, eccentric hypertrophy) using American Society ...

  9. Arritmias ventriculares e hipertrofia ventricular esquerda na cardiomiopatia hipertrófica Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Beatriz Piva e Mattos

    2013-05-01

    Full Text Available FUNDAMENTO: Na Cardiomiopatia Hipertrófica (CMH, o grau de Hipertrofia Ventricular Esquerda (HVE poderia influenciar o desenvolvimento de arritmias ventriculares. OBJETIVO: Analisar, na CMH, a associação entre a ocorrência de arritmias ventriculares no eletrocardiograma-Holter (ECG-Holter e o grau de HVE determinado ao ecocardiograma pela espessura parietal máxima (EPM e Índice de Massa (IM. MÉTODOS: Cinquenta e quatro pacientes consecutivos com CMH realizaram ECG-Holter de 24 horas e ecocardiograma para avaliação do grau de HVE através da EPM e IM. Foram estabelecidos dois níveis para a ocorrência de arritmias ventriculares: I - extrassístoles isoladas ou pareadas e II - Taquicardia Ventricular Não Sustentada (TVNS. RESULTADOS: Nos 13 pacientes (24% com TVNS (nível II, houve maior frequência de EPM do ventrículo esquerdo (VE > 21 mm (n = 10, 77%; 25 ± 4 mm e IMVE > 144 g/m² (n = 10, 77%; 200 ± 30 g/m², em relação àqueles que apresentavam apenas arritmia extrassistólica (nível I (n = 41, 76%, em que essas medidas foram identificadas em, respectivamente, 37% (n = 15, 23 ± 1 mm, p = 0,023, e 39% (n = 16, 192 ± 53 g/m² dos casos, p = 0,026. Os citados valores de corte foram determinados por curva ROC com intervalo de confiança de 95%. O registro de TVNS foi mais comum em pacientes com EPMVE > 21 mm e IMVE > 144 g/m² (8 de 13; 62%, do que naqueles com uma (4 de 13; 31% ou nenhuma (1 de 13; 8% variável ecocardiográfica acima dos valores de corte, p = 0,04. CONCLUSÃO: A ocorrência de arritmias ventriculares no Holter associou-se, na CMH, ao grau de HVE, avaliado pelo ecocardiograma através da respectiva EPM e IM.BACKGROUND: In hypertrophic cardiomyopathy (HCM, the degree of left ventricular hypertrophy (LVH could influence the development of ventricular arrhythmias. OBJECTIVE: In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter and the degree of LVH determined by maximum wall thickness (MWT in echocardiography and body mass index (BMI. METHODS: Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT. RESULTS: In 13 patients (24% with NSVT (level II, there was a higher frequency of MWT of the left ventricle (LV > 21 mm (n = 10, 77%, 25 ± 4 mm and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m², in comparison with those presenting with extrasystole arrhythmias (level I (n = 41, 76%, in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm, p = 0.023, and 39% (n = 16, 192 ± 53 g / m² of the cases (p = 0.026. The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62% than in those with (4 of 13, 31% or without (1 of 13; 8% echocardiographic variables above cut-off values (p = 0.04. CONCLUSION: In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

  10. Arritmias ventriculares e hipertrofia ventricular esquerda na cardiomiopatia hipertrófica / Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy

    Scientific Electronic Library Online (English)

    Beatriz Piva e, Mattos; Marco Antonio Rodrigues, Torres; Valéria Centeno de, Freitas; Fernando Luís, Scolari; Melina Silva de, Loreto.

    2013-05-01

    Full Text Available FUNDAMENTO: Na Cardiomiopatia Hipertrófica (CMH), o grau de Hipertrofia Ventricular Esquerda (HVE) poderia influenciar o desenvolvimento de arritmias ventriculares. OBJETIVO: Analisar, na CMH, a associação entre a ocorrência de arritmias ventriculares no eletrocardiograma-Holter (ECG-Holter) e o gra [...] u de HVE determinado ao ecocardiograma pela espessura parietal máxima (EPM) e Índice de Massa (IM). MÉTODOS: Cinquenta e quatro pacientes consecutivos com CMH realizaram ECG-Holter de 24 horas e ecocardiograma para avaliação do grau de HVE através da EPM e IM. Foram estabelecidos dois níveis para a ocorrência de arritmias ventriculares: I - extrassístoles isoladas ou pareadas e II - Taquicardia Ventricular Não Sustentada (TVNS). RESULTADOS: Nos 13 pacientes (24%) com TVNS (nível II), houve maior frequência de EPM do ventrículo esquerdo (VE) > 21 mm (n = 10, 77%; 25 ± 4 mm) e IMVE > 144 g/m² (n = 10, 77%; 200 ± 30 g/m²), em relação àqueles que apresentavam apenas arritmia extrassistólica (nível I) (n = 41, 76%), em que essas medidas foram identificadas em, respectivamente, 37% (n = 15, 23 ± 1 mm), p = 0,023, e 39% (n = 16, 192 ± 53 g/m²) dos casos, p = 0,026. Os citados valores de corte foram determinados por curva ROC com intervalo de confiança de 95%. O registro de TVNS foi mais comum em pacientes com EPMVE > 21 mm e IMVE > 144 g/m² (8 de 13; 62%), do que naqueles com uma (4 de 13; 31%) ou nenhuma (1 de 13; 8%) variável ecocardiográfica acima dos valores de corte, p = 0,04. CONCLUSÃO: A ocorrência de arritmias ventriculares no Holter associou-se, na CMH, ao grau de HVE, avaliado pelo ecocardiograma através da respectiva EPM e IM. Abstract in english BACKGROUND: In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. OBJECTIVE: In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holt [...] er) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). METHODS: Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). RESULTS: In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). CONCLUSION: In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

  11. Obesity and left ventricular hypertrophy: the hypertension connection.

    Science.gov (United States)

    Woodiwiss, Angela J; Norton, Gavin R

    2015-04-01

    The detection of left ventricular hypertrophy (LVH) is recommended for risk prediction, and changes in LV geometry may provide further prognostic information. Obesity is a major determinant of LVH, but the approach to LVH detection in obese hypertensives remains a challenge. In the present review, we discuss evidence leading to the recent acceptance of the use of LV mass indexed to height(2.7) or height(1.7) rather than body surface area, for LVH detection and its regression in obesity. We also review recent findings which indicate that obesity-induced LVH may be associated with concentric LV remodeling, and hence, that the presence of concentric LVH in obesity should not be assumed to indicate a cause of LVH other than obesity. We also discuss recent evidence for obesity and blood pressure producing additive and interactive effects on LV mass, and hence, that weight loss and blood pressure reduction are required to achieve appropriate regression. PMID:25794954

  12. Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes

    OpenAIRE

    Shenouda, Sylvia K.; Varner, Kurt J.; Carvalho, Felix; Lucchesi, Pamela A.

    2009-01-01

    Repeated administration of MDMA (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown; oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included: al...

  13. The morphological patterns of left ventricular hypertrophy and left ventricular performance in essential hypertensives

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) was performed in 27 patients with essential hypertension (EHT), in whom the ventricular septum or left ventricular free wall or both was 12 mm or more in thickness on two-dimensional echocardiograms, and four healthy volunteers to determine the morphology of left ventricular hypertrophy (LVH). The morphological appearances of LVH were divided into four types: (1) diffuse (D) type in which the entire left ventricle was diffusely thickened (n = 11); (2) free wall (F) type in which the free wall was much more thickened than the other sites (n = 8); (3) apical (A) type in which the thickness was limited to the apical site (n = 5); (4) septal (S) type in which the ventricular septum was asymmetrically thickened (n = 3). Ejection fraction (EF), 1/3 filling fraction, and time to peak filling rate, as determined by blood pool scintigraphy, were used as systolic and diastolic function indices. Groups of both D-type and F-type patients had normal systolic function, depressed diastolic function, and decreased cardiac reserve. The group of A-type patients had a marked decrease in both systolic and diastolic functions, and normal cardiac reserve. In the last group of S-type patients, systolic function was hyperkinetic, diastolic function was decreased, and cardiac reserve was normal. In cases or LVH, left ventricular performance was found to vary according to the morphology of LVH. (Namekawa, K.)

  14. Prevalencia de hipertrofia ventricular izquierda en pacientes hipertensos / Prevalence of left ventricular hypertrophy in hypertensive patients

    Scientific Electronic Library Online (English)

    Fred Gustavo, Manrique; Juan Manuel, Ospina; Giomar Maritza, Herrera-Amaya.

    2014-07-01

    Full Text Available Antecedentes: se ha documentado a la hipertrofia ventricular izquierda como una de las manifestaciones tempranas de afectación cardiaca en la enfermedad hipertensiva. Objetivo: evaluar la prevalencia de hipertrofia ventricular izquierda en los pacientes hipertensos que asisten a los programas de con [...] trol en instituciones de salud de Boyacá. Material y métodos: mediante muestreo secuencial aleatorio se ensambló una muestra de 1275 pacientes a quienes se realizó valoración de la presión arterial y electrocardiograma. Se evaluaron criterios de Cornell, Romhilt-Estest y Rodríguez-Padial para determinar la presencia de hipertrofia ventricular izquierda. Resultados: se encontró prevalencia global de 17.9% de HVI en los pacientes analizados, con marcadas diferencias por municipio. La HVI se encontró asociada con edad mayor de 65 años, sexo femenino, índice de masa corporal aumentado y cifras elevadas de presión sistólica y diastólica. Conclusión: estos resultados sugieren la necesidad de incrementar los programas de tamizaje y control de la presión arterial, así como de incluir capacitación a los agentes de salud en la valoración de evidencia sugestiva de HVI como alteraciones electrocardiográficas y diferencias en las presionesentre las dos extremidades superiores. Abstract in english Background: left ventricular hypertrophy has been documented as one of the early manifestations of cardiac involvement in hypertensive disease. Objectives: to assess the prevalence of left ventricular hypertrophy in hypertensive patients attending control programs in health institutions of Boyacá. M [...] aterials and methods: by sequential random sampling, a sample of 1275 patients for whom assessment of blood pressure and electrocardiogram was performed, was assembled. Cornell, Romhilt-ESTest and Rodriguez-Padial criteria were evaluated to determine the presence of left ventricular hypertrophy. Results: overall prevalence of LVH in the patients studied was 17.9%, with marked differences respect to the village of origin. LVH was found associated with age over 65, female gender, increased body mass index and high levels of systolic and diastolic pressure. Conclusion: these results suggest the need for increased screening programs and control of blood pressure as well as include training to health workers in assessing suggestive evidence of LVH as electrocardiographic changes and differences in pressure between the two upper limbs.

  15. Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy.

    Science.gov (United States)

    Skrabek, R Q; Anderson, J E

    2001-02-01

    We tested the hypothesis that treatment of mdx mouse muscular dystrophy with the glucocorticoid deflazacort prevents cardiomyopathic lesions and is accompanied by changes in metabolism and gene expression that reflect the improved tissue integrity. Cardiac muscle pathology, expression of alpha-cardiac myosin heavy chain, DNA synthesis, laminin, and basic fibroblast growth factor (bFGF) were examined to characterize dystrophy and changes with treatment. The potential of proton magnetic resonance spectroscopy (H-NMRS) to track cardiac dystrophy and deflazacort effects was also studied. Deflazacort (but not equipotent prednisone) reproducibly decreased lesion prevalence and severity. Treatment also produced cardiomyocyte hypertrophy and a 5.4-fold increase in alpha-cardiac myosin content. Expression of bFGF messenger RNA (mRNA), notable around lesions, rose 3.3-fold, and laminin expression rose 2.1-fold after deflazacort. Studies using H-NMRS showed a cardiac "signature" with less glycine and taurine than limb muscle or diaphragm and shifts with progression of dystrophy (distinct from normal aging) in many metabolites. Increased taurine, acetate, and succinate were present after 2 weeks of deflazacort treatment but were not present after 4 weeks. Although paired kinetic and functional studies of myocardium will be needed to determine the origin of such changes, these results demonstrate the potential application of H-NMRS to monitor clinical heart disease and treatment. In addition, the metabolic effects of deflazacort were substantial in preventing the progression of cardiomyopathy in mdx mice and included increased expression of protectant and stabilizing factors and hypertrophy of cardiac myocytes. PMID:11180202

  16. Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

    OpenAIRE

    Celso Ferreira Filho; Luiz Carlos de Abreu; Valenti, Vitor E.; Marcelo Ferreira; Adriano Meneghini; José Alexandre Silveira; Pe?rez Riera, Andre?s R.; Eduardo Colombari; Neif Murad; Paulo Roberto Santos-Silva; Lovian José Henrique Pereira da Silva; Luiz Carlos Marques Vanderlei; Carvalho, Tatiana D.; Celso Ferreira

    2010-01-01

    OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs o...

  17. PERIOPERATIVE PERIOD FOLLOWING HEART TRANSPLANTATION WITH SEVERE LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2012-05-01

    Full Text Available Use donor hearts with left ventricular hypertrophy (LVH is controversial. This category of heart recipients has increasing risk of early graft failure. We proposed that heart transplantation (HT with LVH ?1.5 cm may be successful if performed in selective category patients from alternate transplant list. This study included 10 pati- ents (2 female and 8 male at the age 26–62 (44 ± 3, who needed urgent HT. This study showed that recipients with LVH ?1.5 cm demanded more high and long inotropic support with adrenalin and dopamine, more fre- quent use of levosimendan infusion (in 40% of cases and intraaortic balloon conterpulsation (in 50% of cases. However we didn’t observed any difference in survival rate (90.0% vs 89.0% and ICU time (4.8 ± 0.6 days vs 4.1 ± 0.4 days between HT recipients with and without LVH. Our study showed that HT from donor with LVH ?1.5 cm may be performed in patients, demanding urgent HT, with acceptable early posttransplant results. 

  18. Echocardiographic Partition Values and Prevalence of Left Ventricular Hypertrophy in Hypertensive Jamaicans

    OpenAIRE

    Chiranjivi Potu; Edwin Tulloch-Reid; Dainia Baugh; Olusegun A Ismail; Ernest C. Madu

    2012-01-01

    Left ventricular hypertrophy (LVH) detected by either electrocardiography or echo- cardiography has been shown to be an extremely strong predictor of morbidity and mortality in patients with essential hypertension and in members of the general population. Alternative to LVH, left ventricular geometrical patterns offer incremental prognostic value beyond that provided by the other cardiovascular risk factors including left ventricular mass (LVM). Combination of LVM and relative wall thickness ...

  19. Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes.

    OpenAIRE

    Scriven, D R; Dan, P; Moore, E. D.

    2000-01-01

    We have examined the distribution of ryanodine receptors, L-type Ca(2+) channels, calsequestrin, Na(+)/Ca(2+) exchangers, and voltage-gated Na(+) channels in adult rat ventricular myocytes. Enzymatically dissociated cells were fixed and dual-labeled with specific antibodies using standard immunocytochemistry protocols. Images were deconvolved to reverse the optical distortion produced by wide-field microscopes equipped with high numerical aperture objectives. Every image showed a well-ordered...

  20. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes.

    OpenAIRE

    J Ibarra; Morley, G E; Delmar, M

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

  1. Multiphysics model of a rat ventricular myocyte: A voltage-clamp study

    OpenAIRE

    Krishna Abhilash; Valderrábano Miguel; Palade Philip T; John, W

    2012-01-01

    Abstract Background The objective of this study is to develop a comprehensive model of the electromechanical behavior of the rat ventricular myocyte to investigate the various factors influencing its contractile response. Methods Here, we couple a model of Ca2 + dynamics described in our previous work, with a well-known model of contractile mechanics developed by Rice, Wang, Bers and de Tombe to develop a composite multiphysics model of excitation-contraction coupling. This comprehensive cell...

  2. A new electrocardiographic left ventricular hypertrophy prognostic score.

    Science.gov (United States)

    Jindal, Akash; Singla, Varun; Pargaonkar, Vedant; Froelicher, Victor

    2015-04-01

    This report determines if the classic Romhilt-Estes score would predict better if points for its components were determined using a Cox hazard model and if the Cornell voltage criteria should replace the original criteria. Of the 20,903 subjects, the mean age was 43 ± 10 years and 90.6% were men. The mean follow-up for the population was 17 years, with 881 cardiovascular deaths; they were tested from 1987 to 1999 and followed until 2013. The new score was created with multipliers based on the Cox hazards of its elements with age bracket and gender included. The Cornell criteria were analyzed individually using Cox hazards with and without adjustments for age, gender, and African-American ethnicity and subsequently incorporated into the new score for analysis. For the new score, all 7 components were significant predictors of cardiovascular mortality with gender producing the greatest hazard ratio (HR) and left axis deviation and QRS duration >110 ms producing the lowest. For the original Romhilt-Estes score, 367 patients (1.8%) met the "definite" cutoff and had an HR of 5.6 (95% confidence interval 4.3 to 7.1). For the new score, 208 patients (1.0%) met the "definite" left ventricular hypertrophy cutoff and had an HR of 13.6 (95% confidence interval 10.8 to 17.3). The Romhilt-Estes had an area under the curve of 0.63, whereas the new score and new score with Cornell voltage both had an area under the curve of 0.7. In conclusion, our modified Romhilt-Estes score with new multipliers and without voltage criteria outperformed the original score. PMID:25700803

  3. Non-invasive electrical markers in patients with left ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Nadia Sánchez Torres

    2011-01-01

    Full Text Available Introduction The left ventricular hypertrophy is related with the genesis of ventricular arrhythmiasand sudden death. Depending of the cause, different histologycalmodifications that generate different arrhythmogenic substrates, takesplace. However, few bibliographical evidences exist about the characterizationof these, with non-invasive electrical markers.Objetive To determine the presence of non-invasive electrical markers in patients withleft ventricular hypertrophy of different causes, and to relate the magnitude,of the same one, with the presence of non-invasive electrical markers.Method In the descriptive study 107 patients, with ecocardiographic diagnosis ofleft ventricular hypertrophy were included. They were assisted at the Institutode Cardiología y Cirugía Cardiovascular, between January 2005 andDecember 2007. They were classified in groups according to the ethiologyof the left ventricular hypertrophy: Pathological left ventricular hypertrophy?that included the patients with left ventricular hypertrophy generated byhigh blood pressure, aortic stenosis and hypertrophic cardiomyopathy?,and physiologic left ventricular hypertrophy ?group formed by athletesfrom the national teams of oar and swimming. They were also included, 35seemingly healthy fellows without left ventricular hypertrophy as controlgroup. We obtained a high resolution electrocardiogram at rest of twelvesimultaneous derivations to determine: the late potentials, the QTc interval,the QT special dispersion, the Tp-Te interval and the Tp-Te dispersion; also,the correlation between these markers and the magnitude of left ventricularhypertrophy was stablished.Results The non-invasive electrical markers prevailed in the group of patients withleft ventricular hypertrophy of pathological cause: the late potentials werepositive in the 37,8% and the abnormal QT space dispersion in 18,3% bothwere statistically significant, the prolonged QTc interval was present in21,9% and the mean Tp-Te dispersion was 48,7±24,9ms, in a non significantway, when comparing them with the group of physiologic cause andthe control group. In the group of pathological left ventricular hypertrophythere was a prevalence of all markers, in patients with hypertrophic cardiomyopathy:the late potentials were positive in 57,1%, the QT space dispersionwas abnormal in 28,6% and the mean Tp-Te interval133,6±37,4ms in a significant manner, when comparing with those thatpresent, aortic stenosis and high blood pressure. The prolonged QTc interval38,1% and the mean of the Tp-Te dispersion were bigger in thegroup of hypertrophic cardiomyopathy 57,1±32,2 ms, although it was notsignificant in relation with the groups of patients who suffer from aorticstenosis and high blood pressure. All markers had a weak correlation withthe magnitude of left ventricular hypertrophy (r=0,179-0,292; p <0,05.Conclusions We concluded that the studied non-invasive electrical markers were morefrequent in the group of patients with pathological left ventricular hypertrophy,and inside this, in the patients with hypertrophic cardiomyopathy andthat a weak correlation exists between the magnitude of hypertrophy andthe presence of these markers.

  4. The small GTP-binding protein Rac1 induces cardiac myocyte hypertrophy through the activation of apoptosis signal-regulating kinase 1 and nuclear factor-kappa B.

    Science.gov (United States)

    Higuchi, Yoshiharu; Otsu, Kinya; Nishida, Kazuhiko; Hirotani, Shinichi; Nakayama, Hiroyuki; Yamaguchi, Osamu; Hikoso, Shungo; Kashiwase, Kazunori; Takeda, Toshihiro; Watanabe, Tetsuya; Mano, Toshiaki; Matsumura, Yasushi; Ueno, Hikaru; Hori, Masatsugu

    2003-06-01

    The small guanine nucleotide-binding protein Rac1 has emerged as an important molecule involved in cardiac myocyte hypertrophy. Recently, we reported on apoptosis signal-regulating kinase (ASK) 1 and a transcriptional factor, nuclear factor-kappaB (NF-kappaB), as novel signaling intermediates in cardiac myocyte hypertrophy. The aim of the study presented here was to clarify the role of Rac1 in the ASK1-NF-kappaB signaling pathway. Infection of isolated neonatal cardiac myocytes with an adenovirus expressing a constitutively active form of Rac1 (RacV12) enhanced the expression of a kappaB-dependent reporter gene construct and induced the degradation of IkappaBalpha. Expression of a degradation-resistant mutant of IkappaBalpha inhibited the RacV12-induced hypertrophic responses, including increases in protein synthesis and atrial natriuretic factor production and the enhancement of sarcomeric organization. An immune complex kinase assay indicated that the expression of RacV12 activated ASK1. Expression of a dominant negative mutant of ASK1 eliminated the RacV12-induced NF-kappaB activation and the biochemical and morphological hypertrophic responses, whereas expression of a dominant negative form of Rac1 attenuated phenylephrine-induced activation of ASK1 and NF-kappaB and cardiac myocyte hypertrophy. These findings suggest that Rac1 induces cardiac myocyte hypertrophy mediated through ASK1 and NF-kappaB. PMID:12672819

  5. Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

    Science.gov (United States)

    Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1?M) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1?M) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1?M in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes. PMID:25711828

  6. Ventricular hypertrophy blocked delayed anesthetic cardioprotection in rats by alteration of iNOS/COX-2 signaling

    OpenAIRE

    Ma, Leilei; Kong, Feijuan; Ge, Hongwei; Liu, Jingquan; Gong, Fangxiao; Xu, Liang; Hu, Bangchuan; Sun, Renhua

    2014-01-01

    The aim of the current study was to determine whether ventricular hypertrophy affects the delayed isoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury. Transverse aortic constriction (TAC) was performed on male Sprague-Dawley rats to induce left ventricular (LV) hypertrophy, then sham-operated or hypertrophied rat hearts were subjected to isoflurane preconditioning (2.1% v/v, 1?h). 24?h after exposure, the hearts were isolated and perfused retrogradely by the Lan...

  7. Effects of rutin from leaves and flowers of buckwheat (Fagopyrum esculentum Moench.) on angiotensin II-induced hypertrophy of cardiac myocytes and proliferation of fibroblasts

    OpenAIRE

    Han, Shu-Ying; Chu, Jin-xiu; Li, Guang-Min; Zhu, Li-Sha; Shi, Rui-Fang

    2010-01-01

    Rutin was isolated from dried leaves and flowers of buckwheat (Fagopyrum esculentum Moench.). The effects of rutin on angiotensin II-induced hypertrophy of cultured cardiac myocytes and proliferation of cardiac fibroblasts of neonatal rats were evaluated by analyzing the cell surface area, measuring the protein synthesis rate through 3H-leucine incorporation, and the MTT method. Rutin (0.8 to 8.0 mg/l) exhibited a strong inhibition on the hypertrophy and proliferation. The results...

  8. Roles of mechano-sensitive ion channels, cytoskeleton, and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes.

    OpenAIRE

    Sadoshima, J; TAKAHASHI, T; Jahn, L.; Izumo, S

    1992-01-01

    Mechanical loading of cardiac and skeletal muscles in vivo and in vitro causes rapid activation of a number of immediate-early (IE) genes and hypertrophy of muscle cells. However, little is known as to how muscle cells sense mechanical load and transduce it into intracellular signals of gene regulation. We examined roles of putative cellular mechanotransducers, mechanosensitive ion channels, the cytoskeleton, and contractile activity in stretch-induced hypertrophy of cardiac myocytes grown on...

  9. Spontaneous Ca Waves in Ventricular Myocytes from Failing Hearts Depend on Ca2+-calmodulin-dependent Protein Kinase II

    OpenAIRE

    Curran, Jerry; Brown, Kathy Hayes; Santiago, Demetrio J.; Pogwizd, Steve; Bers, Donald M.; Shannon, Thomas R.

    2010-01-01

    Increased cardiac ryanodine receptor (RyR)-dependent diastolic SR Ca leak is present in heart failure and in conditions when adrenergic tone is high. Increasing Ca leak from the SR could result in spontaneous Ca wave (SCaW) formation. SCaWs activate the inward Na/Ca exchanger (NCX) current causing a delayed afterdepolarization (DAD), potentially leading to arrhythmia. Here we examine SCaWs in ventricular myocytes isolated from failing and healthy rabbit hearts. Myocytes from healthy hearts di...

  10. Identifying the aetiology of left ventricular hypertrophy in an athlete: importance of lifestyle modification

    OpenAIRE

    Ball, Miriam Jane; Keenan, Niall; Lynch, Mary; Prasad, Sanjay; Gorog, Diana A.

    2009-01-01

    The aetiology of left ventricular hypertrophy (LVH) in an athlete is often difficult to identify. We describe a 29-year-old fitness instructor who was referred for investigation of syncope. He gave a history of intensive weight lifting and anabolic steroid use at supra-therapeutic doses for the preceding 6 years. Electrocardiography showed inferolateral repolarisation abnormalities and a transthoracic echocardiogram demonstrated asymmetrical LVH with reduced left ventricular cavity dimensions...

  11. Validation of an in vitro contractility assay using canine ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ? 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ? Cardiac contractility is an important physiological function of the heart. ? Assessment of contractility is a logical part of pre-clinical drug safety testing. ? There are limited validated assays that predict effects of compounds on contractility. ? Using dog myocytes, we have developed an in vitro cardiac contractility assay. ? The assay predicted the in vivo contractility with a good level of accuracy.

  12. Validation of an in vitro contractility assay using canine ventricular myocytes

    International Nuclear Information System (INIS)

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ? 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ? Cardiac contractility is an important physiological function of the heart. ? Assessment of contractility is a logical part of pre-clinical drug safety testing. ? There are limited validated assays that predict effects of compounds on contractility. ? Using dog myocytes, we have developed an in vitro cardiac contractility assay. ? The assay predicted the in vivo contractility with a good level of accuracy.

  13. Regulation of sarcoplasmic reticulum Ca(2+) release by cytosolic glutathione in rabbit ventricular myocytes.

    Science.gov (United States)

    Mazurek, Stefan R; Bovo, Elisa; Zima, Aleksey V

    2014-03-01

    Of the major cellular antioxidant defenses, glutathione (GSH) is particularly important in maintaining the cytosolic redox potential. Whereas the healthy myocardium is maintained at a highly reduced redox state, it has been proposed that oxidation of GSH can affect the dynamics of Ca(2+)-induced Ca(2+) release. In this study, we used multiple approaches to define the effects of oxidized glutathione (GSSG) on ryanodine receptor (RyR)-mediated Ca(2+) release in rabbit ventricular myocytes. To investigate the role of GSSG on sarcoplasmic reticulum (SR) Ca(2+) release induced by the action potential, we used the thiol-specific oxidant diamide to increase intracellular GSSG in intact myocytes. To more directly assess the effect of GSSG on RyR activity, we introduced GSSG within the cytosol of permeabilized myocytes. RyR-mediated Ca(2+) release from the SR was significantly enhanced in the presence of GSSG. This resulted in decreased steady-state diastolic [Ca(2+)]SR, increased SR Ca(2+) fractional release, and increased spark- and non-spark-mediated SR Ca(2+) leak. Single-channel recordings from RyR's incorporated into lipid bilayers revealed that GSSG significantly increased RyR activity. Moreover, oxidation of RyR in the form of intersubunit crosslinking was present in intact myocytes treated with diamide and permeabilized myocytes treated with GSSG. Blocking RyR crosslinking with the alkylating agent N-ethylmaleimide prevented depletion of SR Ca(2+) load induced by diamide. These findings suggest that elevated cytosolic GSSG enhances SR Ca(2+) leak due to redox-dependent intersubunit RyR crosslinking. This effect can contribute to abnormal SR Ca(2+) handling during periods of oxidative stress. PMID:24334252

  14. Blockade of Na+ current by promethazine in guinea-pig ventricular myocytes.

    OpenAIRE

    Tanaka, H.; Habuchi, Y.; Nishimura, M.; Sato, N.; Watanabe, Y.

    1992-01-01

    1. To elucidate the antiarrhythmic mechanism of promethazine, its effects on the fast Na+ current (INa) were examined in single guinea-pig ventricular myocytes by whole-cell voltage clamp methods. 2. Promethazine blocked INa with a KD of 42.6 microM and Hill's coefficient of 1.1 at a holding potential of -140 mV. 3. The INa blockade was enhanced at a less negative holding potential of -80 mV with a change of KD to 4.4 microM. Although 10 microM promethazine did not change the inactivation tim...

  15. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes.

    OpenAIRE

    Apkon, M.; Nerbonne, J. M.

    1988-01-01

    The effects of alpha 1-adrenergic agonists on the waveforms of action potentials and voltage-gated ionic currents were examined in isolated adult rat ventricular myocytes by the whole-cell patch-clamp recording technique. After "puffer" applications of either of two alpha 1 agonists, phenylephrine and methoxamine, action-potential durations were increased. In voltage-clamped cells, phenylephrine (5-20 microM) or methoxamine (5-10 microM) reduced the amplitudes of Ca2+-independent voltage-acti...

  16. Increase in action potential duration and inhibition of the delayed rectifier outward current IK by berberine in cat ventricular myocytes.

    OpenAIRE

    Sa?nchez-chapula, J.

    1996-01-01

    1. In the present work, the effects of the antiarrhythmic drug, berberine, on action potential and ionic currents of cat ventricular myocytes were studied. 2. Berberine prolonged action potential duration in cat ventricular myocytes without altering other variables of the action potential. 3. The drug at concentrations of 0.3-30 microM blocked only the delayed rectifier (IK) current with an IC50 = 4.1 microM. Berberine produced a tonic block and a phasic block that was increased with the dura...

  17. 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

    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 patients with electrocardiographic LV hypertrophy. M-mode, 2-dimensional, and pulsed Doppler echocardiographic recordings of mitral inflow velocity and isovolumetric relaxation time (IVRT) were obtained in 750 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiography (sex-adjusted Cornell voltage duration criteria or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. The patients' mean age was 67+/-7 years and 44% were women. One hundred forty patients (19%) had normal LV geometric pattern, 79 (11%) had concentric remodeling, 342 (45%) had eccentric LV hypertrophy, and 189 (25%) had concentric LV hypertrophy. A normal LV filling pattern was found in 116 patients (16%),abnormal relaxation in 519 (69%), "pseudonormal" filling was found in 83 (11%), and a restrictive filling pattern in 32 (4%). Prolonged IVRT was associated with LV hypertrophy (p

  18. Influence of left ventricular hypertrophy on infarct size and left ventricular ejection fraction in ST-elevation myocardial infarction

    International Nuclear Information System (INIS)

    Background: Left ventricular hypertrophy (LVH) predisposes to larger infarct size, which may be underestimated by the left ventricular ejection fraction (LVEF) due to supranormal systolic performance often present in patients with LVH. The aim of the study was to compare infarct size and LVEF in patients with ST-segment elevation myocardial infarction (STEMI) and increased left ventricular mass on cardiac magnetic resonance (CMR). Methods: The study included unselected group of 52 patients (61 ± 11 years, 69% male) with first STEMI who had CMR after median 5 days from the onset of the event. Left ventricular hypertrophy (LVH) was defined as left ventricular mass index exceeding 95th percentile of references values for age and gender. Infarct size was assessed with means of late gadolinium enhancement (LGE). Results: LVH was found in 16 patients (31%). In comparison to the rest of the group, patients with LVH had higher absolute and relative infarct mass (p = 0.002 and p = 0.02, respectively). LVH was related to higher prevalence of microvascular obstruction and myocardial haemorrhage and higher number of LV segments with transmural necrosis (p = 0.02, p = 0.01 and p = 0.01, respectively). Despite marked difference in the infarct size between both studied subgroups there was no difference in LVEF and mean number of dysfunctional LV segments. Conclusions: Patients with LVH undergoing STEMI have larger infarct size underestimated by the LV systolic performance in compar by the LV systolic performance in comparison to patients without LVH.

  19. Left ventricular hypertrophy in Turner syndrome : a prospective echocardiographic study

    DEFF Research Database (Denmark)

    Mortensen, Kristian Havmand; Gravholt, Claus HØjbjerg

    2012-01-01

    Cardiovascular risk stratification in Turner syndrome (TS) is difficult. Increased left ventricular mass associates with an adverse prognosis in several settings, and this study aimed to elucidate this risk marker in relation to metabolic and cardiovascular status in TS.

  20. Validation of an in vitro contractility assay using canine ventricular myocytes.

    Science.gov (United States)

    Harmer, A R; Abi-Gerges, N; Morton, M J; Pullen, G F; Valentin, J P; Pollard, C E

    2012-04-15

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ~36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration-effect curves were constructed for each compound in 4-30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6-8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. PMID:22373797

  1. Endocytosis machinery is required for ?1-adrenergic receptor-induced hypertrophy in neonatal rat cardiac myocytes

    Science.gov (United States)

    Morisco, Carmine; Marrone, Chiara; Galeotti, Jonathan; Shao, Dan; Vatner, Dorothy E.; Vatner, Stephen F.; Sadoshima, Junichi

    2008-01-01

    Aims Cardiac hypertrophy by activation of the ?-adrenergic receptor (?AR) is mediated more efficiently by the ?1-AR than by the ?2-AR. We investigated the signalling mechanism by which the ?1-AR mediates cardiac hypertrophy. Methods and results Experiments were performed in cultured neonatal rat cardiomyocytes. Hypertrophy was determined by the protein/DNA content and atrial natriuretic factor transcription. Phosphorylation of Akt and Src was assessed by immunoblotting. Isoproterenol (ISO, 10 µM), a non-selective ?-AR agonist, caused selective downregulation of the ?1-AR (control ?1 vs. ?2: 35 vs. 65%, Bmax 78 ± 4 fmol/mg; 4 h, 10 vs. 90%, 61 ± 5 fmol/mg). Concanavalin A (Con A, 0.5 µg/mL), an inhibitor of endocytosis, prevented downregulation of ?1-ARs by ISO treatment (4 h, 35 vs. 65%, 73 ± 8 fmol/mg), suggesting that ?1-ARs selectively undergo endocytosis. Interference with ?1-AR endocytosis by Con A, carboxyl terminal peptide of ?-AR kinase-1, dominant negative (DN) ?-arrestin-1, or DN dynamin inhibited ?-adrenergic hypertrophy, suggesting that the endocytosis machinery plays a key role in mediating ?-adrenergic hypertrophy. Activation of Akt by the ?1-AR was blocked by inhibition of the endocytosis machinery, suggesting that endocytosis mediates activation of Akt. Akt plays a critical role in ?-adrenergic hypertrophy, since DN Akt blocked ISO-induced hypertrophy. ?-Adrenergic activation of Akt is mediated by Src, which associates with the endocytosis machinery and is necessary and sufficient to mediate ?-adrenergic hypertrophy. Conclusion Activation of the endocytosis machinery is required for activation of Akt, which, in turn, critically mediates ?1-AR-induced cardiac hypertrophy. PMID:18194989

  2. RESPONSES OF HYPERTROPHIED MYOCYTES TO REACTIVE SPECIES: IMPLICATIONS FOR GLYCOLYSIS AND ELECTROPHILE METABOLISM

    OpenAIRE

    Sansbury, Brian E.; Riggs, Daniel W.; Brainard, Robert E.; Salabei, Joshua K.; Jones, Steven P.; Hill, Bradford G.

    2011-01-01

    During cardiac remodeling, the heart generates higher levels of reactive species; yet an intermediate “compensatory” stage of hypertrophy is associated with a greater ability to withstand oxidative stress. The mechanisms underlying this protected myocardial phenotype are poorly understood. We examined how a cellular model of hypertrophy deals with electrophilic insults, such as would occur upon ischemia or in the failing heart. For this, we measured energetics in control and phenylephrine...

  3. Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb in rat cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Matsui Hiroki

    2012-12-01

    Full Text Available Abstract Background Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob and the leptin receptor (ob-R in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes. Results Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR. We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII, endothelin-1 (ET-1, or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb gene were significantly increased 4?weeks after banding, but expression of the short form of the leptin receptor (ob-Ra was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress. Conclusions We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.

  4. Caveolin-3 is Up-Regulated in the Physiological Left Ventricular Hypertrophy Induced by Voluntary Exercise Training in Rats

    OpenAIRE

    Ikuo Yokoyama; Koichiro Kinugawa; Ryozo Nagai; Hitosh Oshikawa; Yoshihiro Ishikawa; Teruhiko Aoyagi

    2002-01-01

    Various substances have been introduced in relation with cardiac hypertrophy almost always with controversy in their roles in signal transduction. Those controversies may attribute to the diversity of cardiac hypertrophy. We previously showed that calcineurin was activated in physiological left ventricular hypertrophy (LVH) induced by voluntary exercise training, but not in decompensated pressure-overload LVH. In the current study, we advanced our search for the differences between the volunt...

  5. Prevalence, Clinical Characteristics, and Outcomes Associated with Eccentric versus Concentric Left Ventricular Hypertrophy In Heart Failure with Preserved Ejection Fraction

    OpenAIRE

    Katz, Daniel H.; Beussink, Lauren; Sauer, Andrew J.; Freed, Benjamin H.; Burke, Michael A.; Shah, Sanjiv J.

    2013-01-01

    While concentric remodeling (CR) and concentric hypertrophy (CH) are common forms of left ventricular (LV) remodeling in heart failure with preserved ejection fraction (HFpEF), eccentric hypertrophy (EH) can also occur in these patients. However, clinical characteristics and outcomes of EH have not been well described in HFpEF. We prospectively studied 402 patients with HFpEF, divided into 4 groups based on LV structure: normal geometry (no LV hypertrophy [LVH] and relative wall thickness [RW...

  6. Lack of regression of left ventricular hypertrophy is associated with higher incidence of revascularization in hypertension: The LIFE Study

    DEFF Research Database (Denmark)

    SØraas, Camilla L; Wachtell, Kristian

    2010-01-01

    Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence of revascularization.

  7. Left ventricular diverticulum with marked hypertrophy of the left ventricular apex revealed by thallium-201 myocardial emission CT

    International Nuclear Information System (INIS)

    A case of left ventricular apical diverticulum with marked hypertrophy of the left ventricular apical wall revealed by thallium-201 myocardial emission CT is reported. A 23-year-old woman was admitted to our hospital for evaluation of chest oppression. She was known to have had a heart murmur soon after birth, but she grew uneventfully, partaking in normal exercise. At the age of 21, she began to feel chest oppression during exercise. As the attacks became frequent, she was admitted to our hospital. Physical examination revealed an ejection systolic murmur in the second left intercostal space. Electrocardiography showed ST depression and T inversion in leads III, a VF and V4-6. M-mode echocardiography was normal. Two-dimensional echocardiography showed a small diverticulum at the apex of the left ventricle, which was also recognized by left ventriculography. It was about 8 x 12 mm in size. Thallium-201 myocardial emission CT disclosed marked uptake in the apex of the left ventricle, suggesting apical hypertrophy. Stress thallium-201 myocardial emission CT was negative. Coronary angiography was normal. The cause of chest oppression in this patient is uncertain, but the small diverticulum and hypertrophy of the cardiac apex may play a role in its pathogenesis. (author)

  8. Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

    OpenAIRE

    Bagg Warwick; Pearl Ann; Wadams Gina; ter Bals Mariska M; Poppe Katrina K; Whalley Gillian A; Somaratne Jithendra B; Doughty Rob N

    2011-01-01

    Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes. Methods Prospective cross-sectional study comparing diagnostic accuracy of E...

  9. Effects of Roselle on arterial pulse pressure and left ventricular hypertrophy in hypertensive patients

    OpenAIRE

    Ahmad I. Al-Shafei; Ola A. El-Gendy

    2013-01-01

    Objectives: To characterize the effects of regular Roselle ingestion on blood pressure and left ventricular hypertrophy (LVH) in patients with established moderate essential hypertension. Methods: This non-randomized quasi-experimental study was conducted in Kafr El-Shaikh, Egypt, for 8 weeks, from September 2012 to November 2012. The effects of a 4-week period of regular Roselle ingestion followed by a 4-week recovery period on systolic blood pressure (SBP), diastolic blood pressure (DBP),...

  10. The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy

    OpenAIRE

    Pang, Hui; Han, Bing; Yu, Tao; Peng, Zhen

    2014-01-01

    Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n?=?32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n?=?8) received 5%GS as control. Cardiac function an...

  11. Prevalence and Determinants of Left Ventricular Hypertrophy in Hypertensive Patients at a Primary Care Clinic

    OpenAIRE

    Ching SM; Chia YC; Wan Azman WA

    2012-01-01

    Left ventricular hypertrophy (LVH) has prognostic significance on cardiovascular mortality and morbidity. However, echocardiography screening for LVH is not routinely done for hypertensive patients in a primary care setting. thus, this quantitative study aims to determine the prevalence and factors associated with LVH in hypertensive patients at a primary care setting. this was a cross-sectional study of 359 consecutive patients with uncomplicated essential hypertension attending a hospital-b...

  12. Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat

    International Nuclear Information System (INIS)

    beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. Radioligand binding and cell purification techniques have been employed to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-[125I] iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. [125I]iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of [125I]iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types

  13. The antioxidant edaravone attenuates pressure overload-induced left ventricular hypertrophy.

    Science.gov (United States)

    Tsujimoto, Ikuko; Hikoso, Shungo; Yamaguchi, Osamu; Kashiwase, Kazunori; Nakai, Atsuko; Takeda, Toshihiro; Watanabe, Tetsuya; Taniike, Masayuki; Matsumura, Yasushi; Nishida, Kazuhiko; Hori, Masatsugu; Kogo, Mikihiko; Otsu, Kinya

    2005-05-01

    The free radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used to treat patients with ischemic brain damage. We and others reported previously that in vitro and in vivo reactive oxygen species (ROS) act as second messengers to develop cardiac hypertrophy. In this study, we used an in vivo murine model of pressure overload-induced cardiac hypertrophy to examine the effects of edaravone on left ventricular hypertrophy. The animals were subjected to the transverse thoracic aorta constriction, and edaravone (10 mg/kg) was infused intraperitoneally twice daily. Seven days after the operation, we observed a significant increase in ROS production in hearts, which was eliminated by the treatment with edaravone. Pressure-overloaded hearts showed a significant increase in left ventricular weight/body weight ratio and the expression level of atrial natriuretic factor mRNA, which were attenuated by edaravone. It also reduced perivascular and intermuscular fibrosis and inhibited pressure overload-induced activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream kinases of c-Jun N-terminal protein kinase and p38 mitogen-activated protein kinase. Edaravone attenuated the hypertrophic response even when the treatment was started after the onset of cardiac hypertrophic response. These findings indicate that edaravone significantly attenuates pressure overload-induced cardiac hypertrophy mediated through its antioxidative function and subsequent inhibition of ASK1 signaling pathway. PMID:15824197

  14. Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

    Science.gov (United States)

    Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J

    2015-04-01

    Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. PMID:25460869

  15. Influence of infrasound exposure on the whole L-type calcium currents in rat ventricular myocytes.

    Science.gov (United States)

    Pei, Zhaohui; Zhuang, Zhiqiang; Xiao, Pingxi; Chen, Jingzao; Sang, Hanfei; Ren, Jun; Wu, Zhenbiao; Yan, Guangmei

    2009-06-01

    This study was designed to examine the effect of infrasound exposure (5 Hz at 130 dB) on whole-cell L-type Ca2+ currents (WLCC) in rat ventricular myocytes and the underlying mechanism(s) involved. Thirty-two adult Sprague-Dawley rats were randomly assigned to infrasound exposure and control groups. [Ca2+](i), WLCC, mRNA expression of the a(1c) subunit of L-type Ca2+ channels (LCC), and SERCA2 protein were examined on day 1, 7, and 14 after initiation of infrasound exposure. Fluo-3/AM fluorescence and the laser scanning confocal microscope techniques were used to measure [Ca2+](i) in freshly isolated ventricular myocytes. The Ca2+ fluorescence intensity (FI), denoting [Ca2+](i) in cardiomyocytes, was significantly elevated in a time-dependent manner in the exposure groups. There was a significant increase in WLCC in the 1-day group and a further significant increase in the 7- and 14-day groups. LCC mRNA expression measured by RT-PCR revealed a significant rise in the 1-day group and a significant additional rise in the 7- and 14-day groups compared with control group. SERCA2 expression was significantly upregulated in the 1-day group followed by an overt decrease in the 7- and 14-day groups. Prolonged exposure of infrasound altered WLCC in rat cardiomyocytes by shifting the steady-state inactivation curves to the right (more depolarized direction) without altering the slope and biophysical properties of I (Ca,L). Taken together, our data suggest that changes in [Ca2+](I) levels as well as expression of LCC and SERCA2 may contribute to the infrasound exposure-elicited cardiac response. PMID:19387569

  16. Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes

    DEFF Research Database (Denmark)

    Stengl, Milan; Volders, Paul G A

    2003-01-01

    In guinea-pig ventricular myocytes, in which the deactivation of slowly activating delayed rectifier potassium current (IKs) is slow, IKs can be increased by rapid pacing as a result of incomplete deactivation and subsequent current accumulation. Whether accumulation of IKs occurs in dogs, in which the deactivation is much faster, is still unclear. In this study the conditions under which accumulation occurs in canine ventricular myocytes were studied with regard to its physiological relevance in controlling action potential duration (APD). At baseline, square pulse voltage clamp experiments revealed that the accumulation of canine IKs could occur, but only at rather short interpulse intervals (<100 ms). With action potential (AP) clamp commands of constant duration (originally recorded at rate of 2 Hz), an accumulation was only found at interpulse intervals close to 0 ms. Transmembrane potential recordings with high-resistance microelectrodes revealed, however, that at the fastest stimulation rates with normally captured APs (5 Hz) the interpulse interval exceeded 50 ms. This suggested that no IKs accumulation occurs, which was supported by the lack of effect of an IKs blocker, HMR 1556 (500 nM), on APD. In the presence of the beta-adrenergic receptor agonist isoproterenol (isoprenaline, 100 nM) the accumulation with AP clamp commands of constant duration was much more pronounced and a significant accumulating current was found at a relevant interpulse interval of 100 ms. HMR 1556 prolonged APD, but this lengthening was reverse rate dependent. AP clamp experiments in a physiologically relevant setting (short, high rate APs delivered at a corresponding rate) revealed a limited accumulation of IKs in the presence of isoproterenol. In conclusion, a physiologically relevant accumulation of IKs was only observed in the presence of isoproterenol. Block of IKs, however, led to a reverse rate-dependent prolongation of APD indicating that IKs does not have a dominant role at short cycle lengths.

  17. Evaluation of cardiac electrophysiological properties in an experimental model of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Schultz, Jacob G; Andersen, Stine

    2015-01-01

    BACKGROUND: Malignant arrhythmias are a major cause of sudden cardiac death in adults with congenital heart disease. We developed a model to serially investigate electrophysiological properties in an animal model of right ventricular hypertrophy and failure. METHOD: We created models of compensated (cHF; n=11) and decompensated (dHF; n=11) right ventricular failure in Wistar rats by pulmonary trunk banding. Healthy controls underwent sham operation (Control; n=13). Surface electrocardiography was recorded from extremities, and inducibility of ventricular tachycardia was evaluated in vivo by programmed stimulation. Isolated right ventricular myocardium was analysed for mRNA expression of selected genes. RESULTS: Banding caused an increased mRNA expression of both connexin 43 and the voltage-gated sodium channel 1.5, as well as a prolongation of PQ, QRS and QTc intervals. Ventricular tachycardia was induced in the majority of banded animals compared with none in the healthy control group. No differences were found between the two degrees of failure in neither the electrophysiological parameters nor inducibility. CONCLUSIONS: The electrophysiological properties of rat hearts subjected to pulmonary trunk banding were significantly changed with increased susceptibility to ventricular tachycardia, but no differences were found between compensated and decompensated right ventricular failure. Furthermore, we demonstrate that in vivo electrophysiological evaluation is a sensitive method to characterise the cardiac electric phenotype in an experimental rat model.

  18. Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

    Directory of Open Access Journals (Sweden)

    Celso Ferreira Filho

    2010-01-01

    Full Text Available OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed, Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor and verapamil (Ca++ channel blocker caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker were similar. Indapamina (diuretic had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1 receptor antagonist produced better results than atenolol (selective ?1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  19. Left Ventricular Hypertrophy: An allometric comparative analysis of different ECG markers

    International Nuclear Information System (INIS)

    Allometry, in general biology, measures the relative growth of a part in relation to the whole living organism. Left ventricular hypertrophy (LVH) is the heart adaptation to excessive load (systolic or diastolic). The increase in left ventricular mass leads to an increase in the electrocardiographic voltages. Based on clinical data, we compared the allometric behavior of three different ECG markers of LVH. To do this, the allometric fit AECG ? + ? (VM) relating left ventricular mass (estimated from ecocardiographic data) and ECG amplitudes (expressed as the Cornell-Voltage, Sokolow and the ECG overall voltage indexes) were compared. Besides, sensitivity and specificity for each index were analyzed. The more sensitive the ECG criteria, the better the allometric fit. In conclusion: The allometric paradigm should be regarded as the way to design new and more sensitive ECG-based LVH markers.

  20. Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17?-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

    OpenAIRE

    Belcher, Scott M.; Chen, Yamei; Yan, Sujuan; Wang, Hong-sheng

    2011-01-01

    Previously we showed that 17?-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response cur...

  1. Increased insulin-like growth factor-I gene expression precedes left ventricular cardiomyocyte hypertrophy in a rapidly-hypertrophying rat model system.

    Science.gov (United States)

    Huang, Chi-Yang; Buchanan, David L; Gordon, Robert L; Sherman, Matthew J; Razzaq, Jamil; White, Karen; Buetow, Dennis E

    2003-12-01

    Chronic pressure overload leads to an increase in the size, i.e. hypertrophy, of cardiomyocytes in the heart. However, the molecular mechanisms underlying this hypertrophy are not understood. Insulin-like growth factor-I (IGF-I) synthesized locally in the heart is known to be associated with the hypertrophic process. So far, however, cardiac IGF-I gene expression in the widely used rat model system has only been shown to be increased when the hypertrophy induced by pressure-overload was already established. Therefore, the question of whether IGF-I serves as an initiating or early-enhancing factor for the cardiac hypertrophy remains unanswered. Here, cardiac hypertension and hypertrophy were rapidly induced in the rat by complete constriction of the abdominal aorta between the origins of the renal arteries. Carotid arterial systolic blood pressure remained unchanged in sham rats but increased rapidly in the pressure-overloaded constricted rats with a sustained hypertension established by 3 days. Hypertrophy of left ventricular (LV) cardiomyocytes in constricted rats also occurred by 3 days. However, this hypertrophy was preceded by increases in LV IGF-I mRNA and protein which occurred within 1 day. These results support the hypothesis that cardiac-synthesized IGF-I is an initiating or early-enhancing factor for hypertrophy of LV cardiomyocytes. PMID:14624474

  2. Ca Sparks Do Not Explain all Ryanodine Receptor-Mediated SR Ca Leak in Mouse Ventricular Myocytes

    OpenAIRE

    Santiago, Demetrio J.; Curran, Jerald W.; Bers, Donald M.; Lederer, W. J.; Stern, Michael D.; Ri?os, Eduardo; Shannon, Thomas R.

    2010-01-01

    Diastolic Ca leak from the sarcoplasmic reticulum (SR) of ventricular myocytes reduces the SR Ca content, stabilizing the activity of the SR Ca release channel ryanodine receptor for the next beat. SR Ca leak has been visualized globally using whole-cell fluorescence, or locally using confocal microscopy, but never both ways. When using confocal microscopy, leak is imaged as “Ca sparks,” which are fluorescent objects generated by the local reaction-diffusion of released Ca and cytosolic i...

  3. Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms

    OpenAIRE

    Silva, Deepa S.; Wilson, Richard M.; Hutchinson, Christoph; Ip, Peter C.; Garcia, Anthony G.; Lancel, Steve; Ito, Masa; Pimentel, David R.; Sam, Flora

    2009-01-01

    Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis. Aldosterone (1 ?M) induced apoptosis by increasing terminal deoxynucleotidyltran...

  4. Cobalt-induced polycythaemia causing right ventricular hypertrophy and ascites in meat-type chickens.

    Science.gov (United States)

    Diaz, G J; Julian, R J; Squires, E J

    1994-03-01

    Cobalt increases the red cell mass in both man and animals by increasing the production of erythropoietin. Since meat-type chickens can develop pulmonary hypertension from increased erythropoiesis and polycythaemia, two trials were conducted to investigate the role of cobalt on broiler chicken erythropoiesis and pulmonary hypertension. The results showed that feeding cobaltous chloride at 500 parts/10(6) to meat-type chickens from 1-day-old for 42 days significantly increased haemoglobin content and, to a lesser extent red blood cell count, and haematocrit. No effect was observed on mean corpuscular volume. Increased haemoglobin content was linearly correlated with pulmonary hypertension as measured by the right ventricle weight to total ventricle weight ratio (RV:TV). Levels of malondialdehyde in cardiac tissue were also correlated with the RV:TV ratio, suggesting that peroxidative damage may be related to ventricular hypertrophy. Chickens fed cobalt showed a significantly higher incidence of right ventricular hypertrophy and right ventricular failure and 18.3% developed ascites. PMID:18671074

  5. Pattern of left ventricular hypertrophy seen on transthoracic echo in patients with hypertensive cardiomyopathy when compared with idiopathic hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Objective: To explore the pattern of left ventricular hypertrophy caused by hypertension and to compare it with idiopathic hypertrophic cardiomyopathy. Methods: The retrospective study was conducted at the echocardiography lab of Rashid Hospital, Dubai, from January 2009 to January 2010. Cases of 11 patients with significant left ventricular hypertrophy (septum >15mm) due to underlying hypertension were analysed and compared with 11 cases of idiopathic hypertrophic cardiography (septum >15mm) to assess the two groups with similar baseline echocardiographic features. Minitab software was used for statistical analysis. Results: Although the pattern of hypertrophy in hypertensive patients was more concentric (n=5; 45%), there was also asymmetrical septal hypertrophy in 4 (36%) cases, particularly the elderly with sigmoid shape septum. There was evidence of resting mid-cavity gradient due to reduced left ventricular end-systolic diameter in 4 (36%) cases. Conclusion: Although the equation between hypertension and left ventricular hypertrophy is more concentric, but it can be associated with left ventricular outflow tract obstruction and significant mid-cavity gradients similar to that seen in idiopathic hypertrophic cardiomyopathy. (author)

  6. Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy.

    Science.gov (United States)

    Stratton, Matthew S; McKinsey, Timothy A

    2015-04-01

    Acetylation of lysine residues within nucleosomal histone tails provides a crucial mechanism for epigenetic control of gene expression. Acetyl groups are coupled to lysine residues by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), which are also commonly referred to as "writers" and "erasers", respectively. In addition to altering the electrostatic properties of histones, lysine acetylation often creates docking sites for bromodomain-containing "reader" proteins. This review focuses on epigenetic control of pulmonary hypertension (PH) and associated right ventricular (RV) cardiac hypertrophy and failure. Effects of small molecule HDAC inhibitors in pre-clinical models of PH are highlighted. Furthermore, we describe the recently discovered role of bromodomain and extraterminal (BET) reader proteins in the control of cardiac hypertrophy, and provide evidence suggesting that one member of this family, BRD4, contributes to the pathogenesis of RV failure. Together, the data suggest intriguing potential for pharmacological epigenetic therapies for the treatment of PH and right-sided heart failure. PMID:25707943

  7. Hipertrofia ventricular izquierda y factores de riesgo cardiovascular en niños y adolescentes hipertensos / Left ventricular hypertrophy and cardiovascular risk factors present in hypertensive children and adolescents

    Scientific Electronic Library Online (English)

    Juan René, Llapur Milián; Raquel, González Sánchez; Acelia, Betancourt Pérez; Doris Yisell, Rubio Olivares.

    2009-06-01

    Full Text Available INTRODUCCIÓN. La hipertrofia ventricular izquierda es la más prominente evidencia de afectación de los órganos diana, causada por la hipertensión en los niños y adolescentes. El ecocardiograma es la herramienta fundamental para su diagnóstico. El principal objetivo de esta investigación fue determin [...] ar la presencia de hipertrofia ventricular izquierda mediante ecocardiograma, en niños y adolescentes con hipertensión arterial esencial y relacionarla con algunos factores de riesgo. MÉTODOS. Se estudiaron 140 niños y adolescentes con hipertensión arterial esencial. Se evaluaron variables demográficas, antropométricas, antecedentes personales y familiares de factores de riesgo cardiovascular y la presencia o no de hipertrofia ventricular izquierda. RESULTADOS. Más de la cuarta parte del total presentó hipertrofia ventricular izquierda. De ellos, la mayor frecuencia correspondió al sexo masculino y al grupo etario de 10 a 14 años, en ambos sexos. Hubo un mayor porcentaje en los menores de 5 años y se estableció una relación estadística significativa con el antecedente personal de bajo peso y alto peso al nacer, y con el antecedente familiar de cardiopatía isquémica. CONCLUSIONES. La hipertrofia ventricular izquierda no es una complicación infrecuente de la hipertensión arterial en la infancia. Abstract in english INTRODUCTION: Left ventricular hypertrophy is the more significant evidence of target organs provoked by hypertension in children and adolescents. Echocardiogram is the main tool for its diagnosis. The main objective of present research was to determine presence of left ventricular hypertrophy be ec [...] hocardiogram in children and adolescents presenting with essential high blood pressure and to relate it with risk factors. METHODS: More of the quarter of total had left ventricular hypertrophy. From them, the great frequency was for male sex and for the age-group from 10 to 14 years in both sexes. There was a greater percentage in those under 5 years and we established a significant statistic relation with the personal low and high birth weight and with the family background of ischemic heart disease. CONCLUSIONS: Left ventricular hypertrophy is a frequent complication of hypertension in childhood.

  8. Asociación de la hipertrofía ventricular izquierda con eventos cardiacos posteriores a intervencionismo coronario percutáneo. Association of left ventricular hypertrophy with cardiac events after percutaneous coronary intervention.

    Directory of Open Access Journals (Sweden)

    Luis R. Llerena Rojas

    2011-01-01

    Full Text Available Introduction: Left ventricular hypertrophy is not included in the prognostic models of cardiacevents after percutaneous coronary intervention.Objective To determine the association of left ventricular hypertrophy with the presenceof cardiac events during 4 years follow-up after percutaneous coronary intervention.Method 80 hypertensive patients without prior revascularization, undergoing successfulpercutaneous coronary intervention with bare-metal stents at the NationalCardiology and Cardiovascular Surgery Institute between December 2002 andApril 2004, were prospectively included. The demographic, clinical and angiographiccharacteristics were included in our database during the procedure.We made a 4 years follow-up.Results Restenosis (p<0.02 was more frequent in the group of hypertensive patientswith hypertrophy of both anterior and posterior left ventricle walls. Univariateregression analysis showed that left ventricular hypertrophy associates with ahigher restenosis incidence (OR 3.12; CI 95% 1.20-8.14.Conclusions Left ventricular hypertrophy is a risk marker of restenosis after percutaneouscoronary intervention. There was no association with any other cardiac eventduring the long follow-up of hypertensive patients.

  9. Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism.

    Science.gov (United States)

    Obis, Èlia; Irazusta, Verónica; Sanchís, Daniel; Ros, Joaquim; Tamarit, Jordi

    2014-08-01

    Friedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Patients with FRDA experience neurologic alterations and cardiomyopathy, which is the leading cause of death. The specific effects of frataxin depletion on cardiomyocytes are poorly understood because no appropriate cardiac cellular model is available to researchers. To address this research need, we present a model based on primary cultures of neonatal rat ventricular myocytes (NRVMs) and short-hairpin RNA interference. Using this approach, frataxin was reduced down to 5 to 30% of control protein levels after 7 days of transduction. At this stage the activity and amount of the iron-sulfur protein aconitase, in vitro activities of several OXPHOS components, levels of iron-regulated mRNAs, and the ATP/ADP ratio were comparable to controls. However, NRVMs exhibited markers of oxidative stress and a disorganized mitochondrial network with enlarged mitochondria. Lipids, the main energy source of heart cells, also underwent a clear metabolic change, indicated by the increased presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase. These results indicate that mitochondria and lipid metabolism are primary targets of frataxin deficiency in NRVMs. Therefore, they contribute to the understanding of cardiac-specific mechanisms occurring in FRDA and give clues for the design of cardiac-specific treatment strategies for FRDA. PMID:24751525

  10. Nucleotides maintain the activity of Cav1.2 channels in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Liu, Shu-Yuan; Xu, Jian-Jun; Minobe, Etsuko; Gao, Qing-Hua; Feng, Rui; Zhao, Mei-Mi; Guo, Feng; Yang, Lei; Hao, Li-Ying; Kameyama, Masaki

    2015-05-01

    The activity of Cav1.2 Ca(2+) channels is maintained in the presence of calmodulin and ATP, even in cell-free patches, and thus a channel ATP-binding site has been suggested. In this study, we examined whether other nucleotides, such as GTP, UTP, CTP, ADP and AMP, could be substituted for ATP in guinea-pig ventricular myocytes. We found that all the nucleotides tested could re-prime the Ca(2+) channels in the presence of 1 ?M calmodulin in the inside-out mode. The order of efficacy was ATP > GTP > UTP > ADP > CTP ? AMP. Thus, the presumed nucleotide-binding site in the channel seemed to favor a purine rather than pyrimidine base and a triphosphate rather than a di- or mono-phosphate group. Furthermore, a high concentration (10 mM) of GTP, UTP, CTP, ADP and AMP had inhibitory effects on the channel activity. These results provide information on the putative nucleotide-binding site(s) in Cav1.2 Ca(2+) channels. PMID:25824040

  11. Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure.

    Science.gov (United States)

    Dodic, M; Samuel, C; Moritz, K; Wintour, E M; Morgan, J; Grigg, L; Wong, J

    2001-09-28

    We have shown that exposure of pregnant ewes to dexamethasone (11.5 mg/d for 2 days) at 27 days of gestation (term, 150 days) led to increased blood pressure and cardiac output in adult offspring. In this study, we hypothesized that dexamethasone-induced hypertension is associated with left ventricular hypertrophy and a reduced cardiac functional reserve (CO(max-0)). Six control animals (group C) and five dexamethasone-exposed animals (group D) were volume-loaded with Hemaccel until the wedge pressure was 13 mm Hg (baseline). The wedge pressure was held constant during an infusion of dobutamine at incremental doses (0.4 to 12 microgram/kg/min) while blood pressure and cardiac output were measured. The same protocol was repeated in each animal 5 days later under mild general anesthesia (1.5% isoflurane), when transthoracic echocardiography (M-mode) was obtained. Group D showed a reduced CO(max-0) in response to dobutamine during both conscious (89+/-22 versus 150+/-25 mL/kg/min in control; P<0.01) and anesthetized states (91+/-38 versus 156+/-56 mL/kg/min in control; P<0.05). Reduced CO(max-0) in group D was associated with higher left ventricular mass index compared with group C (2.6+/-0.67 versus 1.8+/-0.51 g/kg; P<0.05). In addition, group D showed a reduced cardiac contractility reserve (FS(max-0)) in response to dobutamine (21+/-22% versus 54+/-34% in group C; P<0.05). An impaired cardiac functional reserve in group D was associated with increased left ventricular type I collagen content. In conclusion, brief prenatal exposure to dexamethasone led to the development of hypertension, left ventricular hypertrophy, and reduced cardiac functional reserve in adult life. PMID:11577028

  12. Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy.

    Science.gov (United States)

    Gupta, A; Schiros, C G; Gaddam, K K; Aban, I; Denney, T S; Lloyd, S G; Oparil, S; Dell'Italia, L J; Calhoun, D A; Gupta, H

    2015-04-01

    We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, Prelaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH. PMID:25231508

  13. Improvement of diastolic function after regression of left ventricular hypertrophy / Mejora de la función diastólica tras regresión de la hipertrofia ventricular izquierda

    Scientific Electronic Library Online (English)

    Raúl, Teniente-Valente; Sergio, Solorio; Enrique, Vargas-Salado; Carlos, Aguirre-Vázquez; Martha A, Hernández-González; José Antonio, Olvera-Lopez; Leticia, Rodríguez-Mariscal; Miguel Angel, Luna-Ruiz; José Manuel, Guillén Contreras; Blanca Olivia, Murillo Ortiz.

    2008-12-01

    Full Text Available Objetivo: Evaluar la función diastólica después de revertir la hipertrofia ventricular izquierda, en hipertensión leve a moderada tratada con inhibidores de la enzima convertidora angiotensina (ECA) y, si era necesario, con un diurético. Métodos: Noventa y ocho pacientes hipertensos con hipertrofia [...] ventricular izquierda e índices de función diastólica anormal del ventrículo izquierdo recibieron captopril 50 a 200 mg/día (Capotena®) más clortalidona durante 12 meses para lograr el control de la presión arterial, definido como presión diastólica Abstract in english Objective: To evaluate the diastolic function after regression of left ventricular hypertrophy, in mild to moderate hypertension treated with angiotensin converting enzyme(ACE) inhibitor and, if necessary, with a diuretic. Methods: Ninety-eight hypertensive patients with left ventricular hypertrophy [...] (LVH) and abnormal left ventricle diastolic function indexes received captopril (Capotena® ) 50 to 200 mg/day plus chlortalidone during 12 months to reach blood pressure control, defined as a diastolic blood pressure

  14. Left ventricular hypertrophy are associated with increased ostial pulmonary vein diameter

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2006-08-01

    Full Text Available Atrial fibrillation (AF, which is called as a global epidemic disease, frequently found in hypertensive patients with left ventricular hypertrophy (LVH. Pulmonary vein (PV, which is known to have an important role in AF initiation and maintenance, increases in its diameter during AF. We sought to investigate PVs diameter changes in LVH with sinus rhythm. Of 70 hypertensive patients with sinus rhythm, 42 subjects demonstrated LVH. The mean ostial diameter of patient with and without LVH, assessed by doing spiral multisliced CT scan in the axial plane, were as follow: right superior (RSPV of 19.6±2.78 vs 17.8±1.93 (p = 0.003, right inferior (RIPV of 18.4±3.12 vs 16.0±2.19 (p < 0.001, left superior (LSPV of 18.1±2.62 vs 16.0±2.16 (p < 0.001, and left inferior (LIPV of 15.9±1.93 vs 15.4±1.85 mm (p = 0.284, respectively. Even during sinus rhythm, LVH causes PV dilation. This result might give an explanation of frequent AF prevalence in hypertensive patients. (Med J Indones 2006; 15:173-6 Keywords: Pulmonary veins, Left ventricular hypertrophy

  15. Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

    DEFF Research Database (Denmark)

    Ravn, Nathja; Zois, Nora E

    2014-01-01

    OBJECTIVES: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. DESIGN: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight pigs died and seven were excluded due to mediastinal infection (n = 2) or failure to produce MR (n = 5). Thus, 28 pigs were included and were divided into three groups: controls (n = 12), mild MR (mMR; n = 10), and moderate to severe MR (sMR; n = 6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. CONCLUSIONS: A new model for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.

  16. 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

    2010-01-01

    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 with electrocardiographic LV hypertrophy who underwent echocardiography at baseline and annually thereafter during randomized losartan- or atenolol-based antihypertensive treatment were followed for a mean of 4.6 years. The composite cardiovascular end point was the first occurrence of fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and cardiovascular mortality. Antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28% to 46% of patients. Although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral 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 into account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling was strongly associated with a reduced risk for hospitalization for heart failure.

  17. Effects of levosimendan in patients with left ventricular hypertrophy undergoing aortic valve replacement

    DEFF Research Database (Denmark)

    Juhl-Olsen, P; Jakobsen, C-J

    2014-01-01

    BACKGROUND: Left ventricular hypertrophy is associated with adverse outcomes, including death, during cardiac surgery. This may be facilitated by an increased oxygen demand and diastolic dysfunction. Levosimendan augments haemodynamics without further oxygen consumption and improves echocardiographic indices of diastolic dysfunction. This study aimed to describe the haemodynamic effects of short-term pre- and intra-operative levosimendan infusion including advanced echocardiographic measures of diastolic and systolic heart function. METHODS: The study was randomised, double-blinded and placebo-controlled performed at a single-centre university hospital. Patients with left ventricular hypertrophy and ejection fraction >?45% scheduled for single procedure aortic valve replacement were included and randomised to infusion of either levosimendan 0.1??g/kg/min or placebo from 4?h before anaesthesia to the end of surgery. Outcome measures were echocardiographic indices of left ventricular diastolic function: E/e' (primary endpoint), e', e'/a' and indices of systolic function: longitudinal strain, ejection fraction and s'. Patients were followed until 6 months after surgery. In addition, invasive haemodynamic measures were obtained perioperatively. RESULTS: The trial was prematurely terminated due to an overall high incidence of post-operative atrial fibrillation (15/20, P?=?0.002) after inclusion of 20 patients. The relative decrease in perioperative cardiac index was lower (P?=?0.016) in the levosimendan group. There was no difference in E/e', and similar results were found for all measures of systolic function. CONCLUSION: Short-term levosimendan caused a transient relative increase in cardiac index, but no effect was seen on the first post-operative day and up to 6 months post-operatively with indices of systolic and diastolic heart function.

  18. The effects of implanted valve sizes on ventricular hypertrophy in aortic stenosis

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    Hikmet Selçuk Gedik

    2012-02-01

    Full Text Available Objective: We aimed to study the effects of the valve sizes according to body surface area on aortic gradient and ventricular hypertrophy in the cases of aortic valve replacement due to isolated aortic stenosis.Methods: Between January 2006 and April 2007, patients (12 men, 15 women; totally 27 followed up prospectively with echocardiography fourth and sixth month postoperatively. The patients were divided into two groups according to the prosthetic aortic valve diameters (19-21 mm vs 23-25 mm. The primary endpoints between the two groups (aortic regurgitation, left ventricular mass index and transvalvular gradient measured by color and continuous wave Doppler were compared. Fischer exact test and Mann-Whitney U test were used for intergroup comparison whereas intragroup analysis was done with Freidman test.Results: Mean systolic gradient and left ventricular mass index were significantly reduced in 23 mm and 25 mm valves (p<0.01 in the postoperative follow-up. In addition, especially, decline in the values of left ventricular mass, left ventricular mass index, peak systolic gradient and the mean systolic gradient were found to be significant. These values associated with regression were detectable at the postoperative 4th month, but actual significant regression was observed at the postoperative 6th month (p<0.01. On the other hand, the values obtained for 19 mm and 21 mm valves also showed significant progress (p<0.05.Conclusion: Factors such as age, gender and activity are important in the selection of appropriate valve sizes in aortic valve replacement. However, the patient's body surface is the most important prognostic factor compared to others.

  19. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: Alterations in left ventricular distribution and utilization

    International Nuclear Information System (INIS)

    Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest. Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH

  20. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: Alterations in left ventricular distribution and utilization

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, C.L.; Kennedy, P.L.; Kulkarni, P.V.; Jansen, D.E.; Gabliani, G.I.; Corbett, J.R. (Univ. of Texas Health Science Center (USA))

    1990-06-01

    Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest. Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.

  1. Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse

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    Elena Ulasova

    2013-01-01

    Full Text Available Hypercholesterolemia is a risk factor for the development of hypertrophic cardiomyopathy. Nevertheless, there are few studies aimed at determining the effects of dietary compounds on early or mild cardiac hypertrophy associated with dyslipidemia. Here we describe left ventricular (LV hypertrophy in 12 week-old Apo E?/? hypercholesterolemic mice. The LV end diastolic posterior wall thickness and overall LV mass were significantly increased in Apo E?/? mice compared with wild type (WT controls. Fractional shortening, LV end diastolic diameter, and hemodynamic parameters were unchanged from WT mice. Oral low dose quercetin (QCN; 0.1 µmol QCN/kg body weight for 6 weeks significantly reduced total cholesterol and very low density lipoprotein in the plasma of Apo E?/? mice. QCN treatment also significantly decreased LV posterior wall thickness and LV mass in Apo E?/? mice. Myocardial geometry and function were unaffected in WT mice by QCN treatment. These data suggest that dietary polyphenolic compounds such as QCN may be effective modulators of plasma cholesterol and could prevent maladaptive myocardial remodeling.

  2. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

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    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for ?-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  3. [3H]-8-cyclopentyl-1,3-dipropylxanthine binding to A1 adenosine receptors of intact rat ventricular myocytes

    International Nuclear Information System (INIS)

    The purpose of the present study was the identification of A1 adenosine receptors in intact rat ventricular myocytes, which are thought to mediate the negative inotropic effects of adenosine. The adenosine receptor antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine was used as radioligand. Binding of the radioligand to intact myocytes was rapid, reversible, and saturable with a binding capacity of 40,000 binding sites per cell. The dissociation constant of the radioligand was 0.48 nM. The adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, xanthine amine congener, and theophylline were competitive inhibitors with affinities in agreement with results obtained for A1 receptors in other tissues. Competition experiments using the adenosine receptor agonists R-N(6)-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine, and S-N(6)-phenylisopropyladenosine gave monophasic displacement curves with Ki values of 50 nM, 440 nM, and 4,300 nM, which agreed well with the GTP-inducible low affinity state in cardiac membranes. The low affinity for agonists was not due to agonist-induced desensitization, and correlated well with the corresponding IC50 values for the inhibition of cyclic AMP accumulation by isoprenaline. It is suggested that only a low affinity state of A1 receptors can be detected in intact rat myocytes due to the presence of high concentrations of guanine nucleotides in intact cells

  4. Reduction of left ventricular ejection fraction on isometric hand grip and cold pressor in hypertensive patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Sustained isometric handgrip (SIHG) and cold pressor (CP) tests are used to assess patients suspected of having coronary artery disease (CAD). The normal response to SIHG and CP is that the blood pressure (BP) increases and left ventricular (LV) ejection fraction (EF) either increases or remains unchanged. Both SIHG and CP tests have been shown to reduce LVEF in patients with CAD. We have assessed the effects of SIHG and CP using radionuclide angiography (RA) in hypertensive patients out of which 10 had left ventricular hypertrophy (LVH group) and 8 had no evidence of LVH (non-LVH group). All patients underwent exercice Thallium-201 (201Tl) imaging in order to rule out CAD. In the LVH group, the mean resting systolic BP (SBP) (210.5 +- 4.7 SE) and diastolic BP (DBP) (119.5 +- 2.3) < mean SBP (237 +- 7.3) and DBP (126 +- 3.1) on SIHG (P<0.0001 and <0.001, respectively). The mean resting EF in LVH group (67 +- 4.3) and the non-LVH group (70 +- 4.3) were similar (P=NS). However, on SIHG and CP the mean EF in LVH group decreased (54 +- 4.6) (P<0.0001) and (62 +- 4.3) (P<0.025) respectively. There were no significant changes in EF on SIHG and CP in the non-LVH group. This finding suggests that while screening patients for CAD using RA, reduction of EF on SIHG and CP may also be due to LVH, resulting in false positive tests for CAD, thus reducing specificity for detection of CAD by these tests

  5. Remodeling of Glucose Metabolism Precedes Pressure Overload -Induced Left Ventricular Hypertrophy: Review of a Hypothesis

    Science.gov (United States)

    Kundu, Bijoy K.; Zhong, Min; Sen, Shiraj; Davogustto, Giovanni; Keller, Susanna R.; Taegtmeyer, Heinrich

    2015-01-01

    When subjected to pressure overload, the ventricular myocardium shifts from fatty acids to glucose as its main source for energy provision and frequently increases its mass. Here, we review the evidence in support of the concept that metabolic remodeling, measured as increased myocardial glucose uptake using dynamic positron emission tomography (PET) with the glucose analogue 2-deoxy-2-[18F]-fluoro-D-glucose (FDG), precedes the onset of left ventricular hypertrophy (LVH) and heart failure. Consistent with this, early intervention with propranolol, which attenuates glucose uptake, prevents the maladaptive metabolic response and preserves cardiac function in vivo. We also review ex vivo studies suggesting a link between dysregulated myocardial glucose metabolism, intracellular accumulation of glucose 6-phosphate (G6P) and contractile dysfunction of the heart. G6P levels correlate with activation of mTOR (mechanistic target of rapamycin) and endoplasmic reticulum stress. This sequence of events could be prevented by pre-treatment with rapamycin (mTOR inhibition) or metformin (enzyme 5?-AMP-activated protein kinase activation ). In conclusion, we propose that metabolic imaging with FDG PET may provide a novel approach to guide the treatment of patients with hypertension-induced LVH. PMID:25791172

  6. The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

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    Randon R.B.

    2005-01-01

    Full Text Available End-stage renal disease (ESRD patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH. The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH levels and left ventricular mass (LVM in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years, 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (280 pg/ml; group III = 21 patients. A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003. LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03. In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

  7. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy

    International Nuclear Information System (INIS)

    201Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r=0.792, r=0.785) and Tl score and LVEF (r=-0.634, r=-0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r=-0.756, r=-0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders. (author)

  8. Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17?-estradiol and the environmental endocrine disruptor bisphenol A.

    Science.gov (United States)

    Belcher, Scott M; Chen, Yamei; Yan, Sujuan; Wang, Hong-Sheng

    2012-02-01

    Previously we showed that 17?-estradiol (E(2)) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca(2+) handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E(2) or BPA on Ca(2+) handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E(2) on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10(-12) M, and the most efficacious concentrations for each were at 10(-9) M. Sensitivity to E(2) and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E(2) suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ER? knockout mouse model showed that ER? and ER? have opposing actions in myocytes and that the balance between ER? and ER? signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E(2) and BPA is dominated by the stimulatory ER?-mediated signaling, and the absence of BPA and E(2) responsiveness in males is due to a counterbalancing-suppressive action of ER?. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ER? and ER? signaling. PMID:22166976

  9. Four-group classification of left ventricular hypertrophy based on ventricular concentricity and dilatation identifies a low-risk subset of eccentric hypertrophy in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper N; Gerdts, Eva

    2014-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients. METHODS AND RESULTS: In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area ?116 and ?96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not. CONCLUSIONS: Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.

  10. Acute effects of levosimendan in experimental models of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Vildbrad, Mads D; Andersen, Asger

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause of death is right ventricular (RV) failure. In this study, we investigated the acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and failure. Wistar rats were randomized to receive sham surgery (n = 8), pulmonary trunk banding (PTB; n = 8), or monocrotaline injection (MCT; n = 7). RV function was evaluated at baseline and after injection of placebo and two concentrations of levosimendan (12 and 60 ?g/kg) using magnetic resonance imaging, echocardiography, and invasive pressure recordings. PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% ± 3.8% [P = 0.0038]; MCT: 9.9% ± 3.1% [P = 0.018]; PTB: 24.5% ± 3.3% [P = 0.0001]; mean ± SEM) compared with placebo. Levosimendan markedly increased RV stroke volume (SV) in the MCT group (29.1% ± 8.3%; P = 0.012), did not change RV SV in the PTB group (0.4% ± 4.5%; P = 0.93), and decreased RV SV in the sham surgery group (-10.9% ± 3.7%; P = 0.020). Nitroprusside, which was used to mimic the systemic arterial vasodilator action of levosimendan, did not influence RV function. These data demonstrate that levosimendan acutely improves the failing right heart in a MCT model of PAH and that the mechanism involves a direct acute positive inotropic effect on the hypertrophic and failing RV of the rat.

  11. Lats2 is a negative regulator of myocyte size in the heart

    Science.gov (United States)

    Matsui, Yutaka; Nakano, Noritsugu; Shao, Dan; Gao, Shumin; Luo, Wenting; Hong, Chull; Zhai, Peiyong; Holle, Eric; Yu, Xianzhong; Yabuta, Norikazu; Tao, Wufan; Wagner, Thomas; Nojima, Hiroshi; Sadoshima, Junichi

    2009-01-01

    Mammalian sterile 20-like kinase 1 (Mst1) plays an important role in mediating apoptosis and inhibiting hypertrophy in the heart. Since Hippo, a Drosophila homologue of Mst1, forms a signaling complex with Warts, a serine/threonine kinase, which in turn stimulates cell death and inhibits cell proliferation, mammalian homologs of Warts, termed Lats1 and Lats2, may mediate the function of Mst1. We here show that Lats2, but not Lats1, dose dependently increased apoptosis in cultured cardiac myocytes. Lats2 also dose-dependently reduced [3H]phenylalanine incorporation and cardiac myocyte size, whereas dominant negative Lats2 (DN-Lats2) increased them, suggesting that endogenous Lats2 negatively regulates myocyte growth. DN-Lats2 significantly attenuated induction of apoptosis and inhibition of hypertrophy by Mst1, indicating that Lats2 mediates the function of Mst1 in cardiac myocytes. Cardiac specific overexpression of Lats2 in transgenic mice significantly reduced the size of left and right ventricles, whereas that of DN-Lats2 caused hypertrophy in both ventricles. Overexpression of Lats2 reduced left ventricular systolic and diastolic function without affecting baseline levels of myocardial apoptosis. Expression of endogenous Lats2 was significantly upregulated in response to transverse aortic constriction (TAC). Overexpression of DN-Lats2 significantly enhanced cardiac hypertrophy and inhibited cardiac myocyte apoptosis induced by TAC. These results suggest that Lats2 is necessary and sufficient for negatively regulating ventricular mass in the heart. Although Lats2 is required for cardiac myocyte apoptosis in response to pressure overload, it was not sufficient to induce apoptosis at baseline. In conclusion, Lats2 affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy. PMID:18927464

  12. Sensitivity and specificity of frequently used electrocardiographic criteria for left ventricular hypertrophy in patients with anterior wall myocardial infarction

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    Hanna, Elias B.; Glancy, D. Luke; Oral, Evrim

    2010-01-01

    Electrocardiographic left ventricular hypertrophy (LVH) strongly predicts mortality in patients with myocardial infarction (MI). However, the validity of LVH voltage criteria in this context has not been assessed. Reviewing the coded database of echocardiographic studies performed at one institution, we performed a retrospective analysis of 49 patients who had anterior akinesis on the echocardiogram and anterior wall MI on the electrocardiogram. Results showed that, compared with the sensitiv...

  13. Association between an ANF gene I/D dimorphism and left ventricular hypertrophy in a Gulf Arab Population

    International Nuclear Information System (INIS)

    An association case-control study was carried out on a group of 151 United Arab Emirates nationals-62 normotensives with and without left ventricular hypertrophy (LVH) and 89 hypertensives, also with and without LVH-with a view to evaluating the value of an intersection/deletion (ID) dimorphism located in the second intron of the human atrial natriuretic factor (ANF) gene in relation to left ventricular hypertrophy. Criteria used for LVH inclusion were: demonstration of Sokoloe and Lyon ECG criteria (sum of S wave in V1 and R wave in lead V5 or V6 > 35 mm) and echocardiography findings (interventricular septum > 1.2 cm; posterior LV wall > 1.3 cm) in the long axis. ANF gene was obtained according to the usual methods by DNA extraction by means of polymerase chain reaction (PCR). The frequencies of this marker were performed according to the Hardy-Weinberg proportions. Our finding show that there was a significant difference in the distribution of the I and D alleles between the two groups (LVH vs non-LVH) with x2 = 12.34, 2df, P=0.002, making this a significant association of the D allele with LVH. Our results do suggest that variants of the ANF gene might be involved in the determination of left ventricular hypertrophy. (author)

  14. Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

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    Bagg Warwick

    2011-04-01

    Full Text Available Abstract Background Left ventricular hypertrophy (LVH is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG for detection of LVH in patients with type 2 diabetes. Methods Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC was calculated. Results 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11 years, BP 134/81 ± 18/11 mmHg, HbA1c 7.3 ± 1.5%. LVH was present in 164 patients (56%. In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p Conclusions LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

  15. Economic benefits of left ventricular hypertrophy regression in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    E.I. Tarlovskaya

    2011-01-01

    Full Text Available Aim. To evaluate by modelling the economic benefits of left ventricular hypertrophy (LVH regression in patients with arterial hypertension (HT due to therapy with fixed combination of valsartan/amlodipine.Material and methods. 20 patients (15 females and 5 males, aged 18 to 70 years with essential HT accompanied by metabolic syndrome with a history of previous ineffective antihypertensive therapy were included into the study. All patients were treated with fixed combination of amlodipine/valsartan in doses of 5/160 and 10/160 mg depending on blood pressure (BP level. Treatment duration was 24 weeks. Changes in BP level, LVH regression were assessed. Economic evaluation was performed on the basis of modelling with the specialized software Decision Tree 4.xla.Results. Effect of fixed amlodipine/valsartan combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to left ventricular (LV mass (at baseline and after 24 weeks of therapy. Significant decrease in LV mass from 205.8±50.4 to 181.9±45.1 g (p<0.05 was revealed. The model took into account economic and frequency factors for 10 year prognosis: this therapy prevents 36 deaths, 6 strokes, 24 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save 2 516 772.42 RUR for every 1 000 patients. It would reduce the total costs per patient during 10 years.Conclusion. Treatment with amlodipine/valsartan single pill combination has not only clinical advantages, but also pharmacoeconomic benefits. This combination reduces risk of acute myocardial infarction and death more effectively. Treatment with fixed valsartan/amlodipine combination saves maximum years of life with less cost during 10 years. Despite of higher pharmacotherapy costs, fixed valsartan/amlodipine combination reduces total costs due to prevention of fatal and nonfatal cardiovascular events.

  16. ?-Adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cAMP metabolism

    International Nuclear Information System (INIS)

    When incubated with purified cardiomyocytes from adult rat ventricle, the ?1-antagonist [3H]prazosin binds to a single class of sites with high affinity. Competition for [3H]prazosin binding by the ?2-selective antagonist yohimbine and the nonselective ?-antagonist phentolamine demonstrates that these receptors are of the ?1-subtype. In addition, incubation of myocyte membranes with [3H]yohimbine results in no measurable specific binding. Agonist competition for [3H]prazosin binding to membranes prepared from purified myocytes demonstrates the presence of two components of binding: 28% of ?1-receptors interact with norepinephrine with high affinity (K/sub D/ = 36 nM), whereas the majority of receptors (72%) have a low affinity for agonist (K/sub D/ = 2.2 ?M). After addition of 10 ?M GTP, norepinephrine competes for [3H]prazosin binding to a single class of sites with lower affinity (K/sub D/ = 2.2 ?M). Incubation of intact myocytes for 2 min with 1 ?M norepinephrine leads to significantly less cyclic AMP (cAMP) accumulation than stimulation with either norepinephrine plus prazosin or isoproterenol. Likewise, incubation of intact myocytes with 10-6 M norepinephrine leads to significantly less activation of cAMP-dependent protein kinase than when myocytes are stimulated by both norepinephrine and the ?1-adrenergic antagonist, prazosin or thergic antagonist, prazosin or the ?-adrenergic agonist, isoproterenol. They conclude that the cardiomyocyte ?1 receptor is coupled to a guanine nucleotide-binding protein, that ?1-receptors are functionally linked to decreased intracellular cAMP content, and that this change in cellular cAMP is expressed as described activation of cAMP-dependent protein kinase

  17. The interdialytic weight gain: a simple marker of left ventricular hypertrophy in children on chronic haemodialysis.

    Science.gov (United States)

    Fischbach, Michael; Zaloszyc, Ariane; Shroff, Rukshana

    2015-06-01

    Despite multiple advances in haemodialysis (HD) technology over the years, the morbidity and mortality of HD patients remain unacceptably high. Cardiovascular disease is the most common cause of death, and left ventricular hypertrophy (LVH), seen in two-thirds of children on dialysis, is a significant contributor. The importance of volume control is increasingly recognized by nephrologists and now considered to be as important as urea kinetics, both in the day-to-day management and the long-term outcome of dialysis patients. The results published by Paglialonga et al. ( 10.1007/s00467-014-3005-2 ) in this issue of Pediatric Nephrology clearly demonstrate that there is a significant correlation between interdialytic weight gain (IDWG) and LVH in oligoanuric children on chronic HD and that children with an IDWG of >4 % are at high risk of LVH. One common practice to achieve euvolaemia is to prescribe very high ultrafiltration rates. However, both volume overload and aggressive fluid removal can induce circulatory stress and multi-organ injury. In adults, ultrafiltration rates of >1.24 % body weight per hour, even if well tolerated, are associated with a significant increase in mortality. Nephrologists should be aware of the risk of a high ultrafiltration rate, especially if tolerance is obtained by a positive dialysate-to-plasma sodium gradient. Haemodiafiltration, which allows for higher ultrafiltration rates with greater intradialytic haemodynamic stability, or more frequent and longer dialysis sessions allow for safe and effective fluid removal. PMID:25797887

  18. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    International Nuclear Information System (INIS)

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion–reaction equations presented by Izu et al (2001 Biophys. J. 80 103–20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameterked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF

  19. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    Science.gov (United States)

    Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

    2010-06-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF.

  20. SERUM IGF-I AND HORMONAL RESPONSES TO INCREMENTAL EXERCISE IN ATHLETES WITH AND WITHOUT LEFT VENTRICULAR HYPERTROPHY

    Directory of Open Access Journals (Sweden)

    Aleksandra Zebrowska

    2009-03-01

    Full Text Available We investigated the response of insulin-like growth factor (IGF- I, insulin-like growth factor binding protein-3 (IGFBP-3 and some hormones, i.e., testosterone (T, growth hormone (GH, cortisol (C, and insulin (I, to maximal exercise in road cyclists with and without diagnosed left ventricular hypertrophy. M-mode and two-dimensional Doppler echocardiography was performed in 30 professional male endurance athletes and a group of 14 healthy untrained subjects using a Hewlett-Packard Image Point HX ultrasound system with standard imaging transducers. Echocardiography and an incremental physical exercise test were performed during the competitive season. Venous blood samples were drawn before and immediately after the maximal cycling exercise test for determination of somatomedin and hormonal concentrations. The basal concentration of IGF-I was statistically higher (p < 0.05 in athletes with left ventricular muscle hypertrophy (LVH when compared to athletes with a normal upper limit of the left ventricular wall (LVN (p < 0.05 and to the control group (CG (p < 0.01. The IGF-I level increased significantly at maximal intensity of incremental exercise in CG (p < 0.01, LVN (p < 0.05 and LVH (p < 0.05 compared to respective values at rest. Long-term endurance training induced an increase in resting (p < 0.01 and post-exercise (p < 0.05 IGF-I/IGFBP-3 ratio in athletes with LVH compared to LVN. The testosterone (T level was lower in LVH at rest compared to LVN and CG groups (p < 0.05. These results indicate that resting serum IGF-I concentration were higher in trained subjects with LVH compared to athletes without LVH. Serum IGF- I/IGFBP-3 elevation at rest and after exercise might suggest that IGF-I act as a potent stimulant of left ventricular hypertrophy in chronically trained endurance athletes

  1. The relation between peripheral vascular structure, left ventricular hypertrophy, and ambulatory blood pressure in essential hypertension

    DEFF Research Database (Denmark)

    Sihm, I; Schroeder, A P

    1995-01-01

    The relations between left ventricular mass (LVM), peripheral resistance artery structure, and ambulatory BP were studied in 83 patients with previously untreated or poorly regulated essential hypertension and 20 healthy controls of similar age and sex. LVM was assessed by echocardiography. Signs of left ventricular hypertrophy (LVH) were present in 67 (81%) of the patients and in none of the controls. Peripheral resistance arteries were isolated from surgical gluteal skin biopsies and mounted in a Mulvany-Halpern isometric small vessel myograph, and their media:lumen ratio, media thickness, and media cross-sectional area were determined under standardized conditions. Mean (+/- SD) ambulatory BP was 122 +/- 9 mm Hg among patients and 96 +/- 8 mm Hg among controls (P <.001). LVM was 327 +/- 99 g among patients and 197 +/- 37 g among controls (P <.001). Media thickness of resistance arteries was 21.0 +/- 4.2 microns among hypertensives and 16.2 +/- 2.6 microns among controls (P <.001). The media:lumen ratio of arteries from patients was 10.2 +/- 2.6% v 7.9 +/- 2.0% in arteries of similar internal diameter from controls (P <.01). Both LVM index (LVMI) and media/lumen ratio correlated significantly with BP. There was significant correlation between media:lumen ratio and LVMI among hypertensive patients (r = 0.45, P <.001), but if patients were subdivided according to the presence of LVH this correlation was found only among patients with LVH (r = 0.60 P<.001) and not among patient without LVH nor controls. Multiple regression analyses of age, body surface area, media/lumen ratio, and BP on LVM or LVMI revealed independent contributions of media/lumen ratio and BP. Age had no influence in the models. Similar results were obtained when casual BP was replaced with ambulatory BP in these analyses. No correlation was found between LVMI and media cross-sectional area. A minor subset of patients with complete absence of nocturnal BP drop had particularly great LVM and media:lumen ratio. The study suggests that cardiac and arteriolar tissue undergo parallel structural remodeling in essential hypertension.

  2. Electrocardiographic left ventricular hypertrophy in GUSTO IV ACS: an important risk marker of mortality in women.

    DEFF Research Database (Denmark)

    Westerhout, Cynthia M; Lauer, Michael S

    2007-01-01

    AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries (GUSTO) IV ACS trial had admission electrocardiograms analysed at a core laboratory. LVH [>or=20 mm Cornell voltage (LV voltage) (women) or >or=28 mm (men) plus strain patterns] was observed in 586 (7.9%) patients, and women accounted for 74%. LVH patients were also older and had more co-morbidities, ST-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P < 0.001). Mortality was significantly higher in patients with LVH (30 day: 5 vs. 3%, P = 0.046; 1 year: 14 vs. 7%, P < 0.001), whereas 30day myocardial infarction (MI) and death/MI did not differ. After baseline adjustment including NT-proBNP, LVH remained associated with increased hazard of 1 year mortality in women, but not in men [P-interaction = 0.033; women: adjusted hazard ratio (LVH vs. no LVH): 1.42 (1.04-1.94), P = 0.029]. CONCLUSION: Electrocardiographic-LVH identifies an important subset of ACS patients with a higher risk of long-term mortality, particularly among women. These novel findings highlight opportunities to improve treatment and outcome among similar ACS patients. Udgivelsesdato: 2007-Sep

  3. The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Wachtell, K.; Devereux, R.B.

    2008-01-01

    The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12

  4. Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

    Directory of Open Access Journals (Sweden)

    MichaelNivala

    2012-05-01

    Full Text Available Intracellular calcium (Ca cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR, mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a varient of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5x5x5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100x20x10 CRUs, a one-second heart time simulation takes about 10 minutes of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.

  5. Plzf as a Candidate Gene Predisposing the Spontaneously Hypertensive Rat to Hypertension, Left Ventricular Hypertrophy, and Interstitial Fibrosis.

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Mancini, M.; Krupková, M.; Chylíková, B.; K?enová, D.; Šeda, O.; Šilhavý, Jan; Mlejnek, Petr; Landa, Vladimír; Zídek, Václav; d´Amati, G.; Pravenec, Michal; K?en, Vladimír

    2014-01-01

    Ro?. 27, ?. 1 (2014), s. 99-106. ISSN 0895-7061 R&D Projects: GA ?R(CZ) GAP301/10/0756; GA ?R(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant ostatní: Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.402, year: 2013

  6. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    Scientific Electronic Library Online (English)

    M.A., Carneiro-Júnior; J.F., Quintão-Júnior; L.R., Drummond; V.N., Lavorato; F.R., Drummond; M.A., Amadeu; E.M., Oliveira; L.B., Felix; J.S., Cruz; J.G., Mill; A.J., Natali; T.N., Prímola-Gomes.

    2014-11-01

    Full Text Available In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise train [...] ing could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ?F/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ?F/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  7. Hipertrofia cardíaca esquerda e direita em necropsias de hipertensos / Left and right ventricular hypertrophy at autopsy of hypertensive individuals

    Scientific Electronic Library Online (English)

    Mirella Pessoa, Sant' Anna; Roberto José Vieira de, Mello; Luciano Tavares, Montenegro; Mônica Modesto, Araújo.

    2012-02-01

    Full Text Available OBJETIVO: Medir a espessura ventricular direita e esquerda em falecidos com história de hipertensão arterial, submetidos a necropsias clínicas. MÉTODOS: Foram selecionados 90 casos do Serviço de Verificação de Óbitos de Recife -PE, de ambos os sexos, com história de hipertensão arterial essencial, c [...] om relação à espessura das paredes cardíacas, além da correlação com outros achados de necropsia e informes clínicos. RESULTADOS: Observouse associação significativa entre a presença de hipertrofia ventricular esquerda (HVE) e direita (HVD), e de cardiopatia hipertensiva grave e HVD. Houve predomínio da HVD e HVE em homens, na faixa etária dos 60-79 anos, com maior prevalência nas etnias parda e negra, e naqueles com estado nutricional adequado ou com sobrepeso e em obesos. CONCLUSÃO: Observou-se que a presença de HVD relaciona-se com HVE, sugerindo que há fatores patogênicos semelhantes envolvidos no desenvolvimento da hipertrofia bilateral. A HVD parece associar-se à doença cardíaca mais grave, podendo, a partir de outros estudos, ser considerada novo fator prognóstico na avaliação dos pacientes hipertensos. Abstract in english OBJECTIVE: To measure the right and left ventricular thickness in deceased individuals with a history of hypertension submitted to clinical autopsies. METHODS: We selected 90 cases from the Death Verification Service of the city of Recife, state of Pernambuco, Brazil, of both sexes, with a history o [...] f essential arterial hypertension related to heart wall thickness, in addition to correlation with autopsy findings and other clinical reports. RESULTS: There was a significant association between the presence of left ventricular hypertrophy (LVH) and right ventricular hypertrophy (RVH) and between severe hypertensive cardiomyopathy and RVH. There was a predominance of RVH and LVH in men aged 60-79 years and a higher prevalence in the Brazilian mulatto and Black ethnic groups and in those with adequate nutritional status or overweight and obese individuals. CONCLUSION: It was observed that the presence of RVH was related to LVH, suggesting that there are similar pathogenic factors involved in the development of bilateral hypertrophy. The RVH seems to be associated with more severe heart disease and may, based on other studies, be considered as a new prognostic factor in the evaluation of hypertensive patients.

  8. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study.

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Okin, Peter M

    2007-01-01

    BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertension (LIFE) study included 9193 patients 55 to 80 years of age with essential hypertension and ECG LV hypertrophy by gender-adjusted Cornell product (CP) (RaVL+SV(3) [+6 mm in women]). QRS duration>2440 mm x ms) and/or Sokolow-Lyon voltage (SLV) (SV1+RV(5/6)>38 mm). During follow-up (mean, 4.8 years), 190 patients (2%) experienced SCD. In time-dependent Cox analyses, absence of in-treatment LV hypertrophy was associated with a decreased risk of SCD: every 1-SD-lower in-treatment CP (1050 mm x ms) was associated with a 28% lower risk of SCD (hazard ratio [HR], 0.72; 95% CI, 0.66 to 0.79) and 1-SD-lower SLV (10.5 mm) with a 26% lower risk (HR, 0.74; 95% CI, 0.65 to 0.84). After adjustment for time-varying systolic and diastolic blood pressures, treatment allocation, age, gender, baseline Framingham risk score, ECG strain, heart rate, urine albumin/creatinine ratio, smoking, diabetes, congestive heart failure, coronary heart disease, atrial fibrillation, and occurrence of myocardial infarction, atrial fibrillation, heart failure, and noncardiovascular death, both in-treatment CP and SLV remained predictive of SCD: each 1-SD-lower CP was associated with a 19% lower risk of SCD (HR, 0.81; 95% CI, 0.73 to 0.90) and 1-SD-lower SLV with an 18% lower risk (HR, 0.82; 95% CI, 0.70 to 0.98). Absence of in-treatment LV hypertrophy by both SLV and CP was associated with a 30% lower risk of SCD (HR, 0.70; 95% CI, 0.54 to 0.92). CONCLUSIONS: Absence of in-treatment ECG LV hypertrophy is associated with reduced risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14

  9. Coronary artery calcification and ECG pattern of left ventricular hypertrophy or strain identify different healthy individuals at risk

    DEFF Research Database (Denmark)

    Diederichsen, SØren Zöga; Gerke, Oke

    2013-01-01

    PURPOSE:: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification. METHOD:: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A noncontrast computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage?×?QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association between the presence of CAC, clinical variables and ECG findings was evaluated by means of multivariate logistic regression. RESULTS:: Of 1825 invited individuals, 1226 accepted the screening. The prevalence of hypertension was 50%. Hypertensive patients frequently had LVH and/or strain when compared with nonhypertensive individuals (21 vs. 14%, P?

  10. Fragmented QRS and Left Ventricular Geometry in Hypertensive Patients

    Directory of Open Access Journals (Sweden)

    Lütfü Bekar

    2013-08-01

    Full Text Available Introduction: Fragmented QRS is a depolarization abnormality detected with routin ECG recording. It is related with conduction defect which occurs after myocardial fibrosis. In the left ventricular hypertrophy, an excessive amount of collagen accumulates in the interstitium when the myocytes became hypertrophied, resulting in myocardial fibrosis. In this study, we aimed to investigate the relationship of fragmented QRS which was detected on ECG recordings of the hypertensive patients with the left ventricular geometry.Patients and Methods: Essential hypertension patients referred to our hospital on outpatient bases were included in the study. 12-lead resting ECG was taken in all the patients. Left ventricular geometry defined using left ventricular mass index and relative wall thickness with transthorasic echocardiography.Results: Sixy seven patients with fragmented QRS and 63 patients without fragmented QRS included the study. We found that patients in the group with fragmented QRS detected have a wider mean left atrium diameter, greater left ventricular mass and left ventricular mass index compared with the group without fragmented QRS. Concentric and eccentric hypertrophy were more common in fragmented QRS group, while normal geometry and concentric remodelling have greater rates in the normal group.Conclusion: Left ventricular hypertrophy is observed more frequently in the patients with fragmented QRS than without fragmented QRS. This may be associated with the increased myocardial fibrosis in the left ventricular hypertrophy. Existence of fragmented QRS can be used for risk stratification in the hypertensive patients.

  11. Nifedipine Inhibits Cardiac Hypertrophy and Left Ventricular Dysfunction in Response to Pressure Overload

    OpenAIRE

    Ago, Tetsuro; Yang, Yanfei; Zhai, Peiyong; Sadoshima, Junichi

    2010-01-01

    Pathological hypertrophy is commonly induced by activation of protein kinases phosphorylating class II histone deacetylases (HDACs) and de-suppression of transcription factors, such as NFAT. We hypothesized that nifedipine, an L-type Ca2+ channel blocker, inhibits Ca2+ -calmodulin dependent kinase II (CaMKII) and NFAT, thereby inhibiting pathological hypertrophy. Mice were subjected to sham operation or transverse aortic constriction (TAC) for 2 weeks with or without nifedipine (10 mg/kg/day)...

  12. Avaliação da redução de gradientes pressóricos e da hipertrofia ventricular após valvoplastia cirúrgica na estenose aórtica Left ventricular hypertrophy regression immediately after aortic valve repair

    Directory of Open Access Journals (Sweden)

    G. R. Hoppen

    2000-10-01

    Full Text Available INTRODUÇÃO: A correção cirúrgica da estenose aórtica resulta em redução significativa do gradiente pressórico transvalvar, sendo acompanhada por regressão da hipertrofia ventricular esquerda(HVE. A intensidade e a rapidez dessa regressão tem sido objeto de avaliações. A associação de valvoplastia aórtica e regressão imediata da HVE é relatada em poucos estudos. MÉTODOS: Foram estudados, prospectivamente, 11 pacientes submetidos à valvoplastia em estenose aórtica, utilizando-se ecocardiografia imediatamente antes da cirurgia e no período pós-operatório precoce (6,1±0,9 dias. RESULTADOS: A espessura septal variou de 12,10±1,66mm para 11,36±1,12mm (redução de 6,1% (NS enquanto a espessura parietal variou 4,4% (de 11,70±1,41 mm para 11,18±1,16mm (NS. A fração de ejeção apresentou uma variação de 62,02± 18,59% para 62,50±11,74% (NS. A massa ventricular esquerda variou em 6,7% ( de 277,65±114,80 g passou para 258,93±92,38 g (NS. O gradiente transvalvular médio regrediu de 53,6±10,3 mmHg para 23,0±9,1mmHg, ou seja, 57% (pBACKGROUND: Relief of gradient is followed by myocardial mass reduction in aortic stenosis. Its degree and speed are under evaluation. Aortic valve repair in calcified aortic stenosis is less well studied than replacement. METHODS: We evaluated left ventricular hypertrophy reduction by echocardiogram in 11 patients immediately after valve repair in aortic stenosis at a mean of 6.1 ± 0.9 days post operative. RESULTS: Septal width was 12.10 ± 1.66 mm pre and 11.36 ± 1.12 mm post operative, 6,1% reduction (NS. Parietal width varied 4.4% from 11.70±1.41 mm to 11.18 ± 1,16 mm (NS. Ejection fraction went from 62.02±18.59% to 62.50±11. 74% (NS. Left ventricular mass varied 6.7%, from 277.65±114.80g to 258.93± 92.38 g (NS. Mean transvalvar gradient reduced 57%, from 53.56±10.30 to 23.0±9.1 mmHg (P<0.001. CONCLUSION: Aortic valve repair reduces gradients adequately and left ventricular hypertrophy shows a trend to regression soon after aortic repair, but is not yet significant in the first post-operatively week.

  13. Effects of bisindolylmaleimide PKC inhibitors on p90RSK activity in vitro and in adult ventricular myocytes.

    Science.gov (United States)

    Roberts, Neil A; Haworth, Robert S; Avkiran, Metin

    2005-06-01

    1 Bisindolylmaleimide inhibitors of protein kinase C (PKC), such as GF109203X and Ro31-8220, have been used to investigate the roles of PKC isoforms in many cellular processes in cardiac myocytes, but these agents may also inhibit p90RSK activity. 2 In in vitro kinase assays utilising 50 microM [ATP], GF109203X and Ro31-8220 inhibited p90RSK isoforms (IC50 values for inhibition of RSK1, RSK2 and RSK3, respectively, were 610, 310 and 120 nM for GF109203X, and 200, 36 and 5 nM for Ro31-8220) as well as classical and novel PKC isoforms (IC50 values for inhibition of PKCalpha and PKCepsilon, respectively, were 8 and 12 nM for GF109203X, and 4 and 8 nM for Ro31-8220). 3 At physiological [ATP] (5 mM), both GF109203X and Ro31-8220 exhibited reduced potency as inhibitors of RSK2, PKCalpha and PKCepsilon (IC50 values of 7400, 310 and 170 nM, respectively, for GF109203X, and 930, 150 and 140 nM, respectively, for Ro31-8220), with the latter agent retaining its relatively greater potency. 4 To determine the effects of GF109203X and Ro31-8220 on p90RSK activity in cultured adult rat ventricular myocytes (ARVM), phosphorylation of the eukaryotic elongation factor 2 kinase (eEF2K) at Ser366, a known p90RSK target, was used as the index of such activity. Adenoviral expression of a constitutively active form of mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) kinase 1 (MEK1) was used to induce PKC-independent p90RSK activation and downstream phosphorylation of eEF2K. 5 eEF2K phosphorylation was abolished by U0126 (1 microM), a selective inhibitor of MEK1, and was significantly reduced by GF109203X at > or =3 microM and by Ro31-8220 at > or =1 microM. At 1 microM, both agents inhibited PMA-induced PKC activity in ARVM. 6 These data show that GF109203X and Ro31-8220 inhibit various isoforms of PKC and p90RSK in vitro and in intact ARVM, with the former agent exhibiting relatively greater selectivity for PKC. PMID:15821757

  14. BET acetyl-lysine binding proteins control pathological cardiac hypertrophy.

    Science.gov (United States)

    Spiltoir, Jessica I; Stratton, Matthew S; Cavasin, Maria A; Demos-Davies, Kim; Reid, Brian G; Qi, Jun; Bradner, James E; McKinsey, Timothy A

    2013-10-01

    Cardiac hypertrophy is an independent predictor of adverse outcomes in patients with heart failure, and thus represents an attractive target for novel therapeutic intervention. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) acetyl-lysine reader proteins, was identified in a high throughput screen designed to discover novel small molecule regulators of cardiomyocyte hypertrophy. JQ1 dose-dependently blocked agonist-dependent hypertrophy of cultured neonatal rat ventricular myocytes (NRVMs) and reversed the prototypical gene program associated with pathological cardiac hypertrophy. JQ1 also blocked left ventricular hypertrophy (LVH) and improved cardiac function in adult mice subjected to transverse aortic constriction (TAC). The BET family consists of BRD2, BRD3, BRD4 and BRDT. BRD4 protein expression was increased during cardiac hypertrophy, and hypertrophic stimuli promoted recruitment of BRD4 to the transcriptional start site (TSS) of the gene encoding atrial natriuretic factor (ANF). Binding of BRD4 to the ANF TSS was associated with increased phosphorylation of local RNA polymerase II. These findings define a novel function for BET proteins as signal-responsive regulators of cardiac hypertrophy, and suggest that small molecule inhibitors of these epigenetic reader proteins have potential as therapeutics for heart failure. PMID:23939492

  15. Cardiac MRI assessed left ventricular hypertrophy in differentiating hypertensive heart disease from hypertrophic cardiomyopathy attributable to a sarcomeric gene mutation

    International Nuclear Information System (INIS)

    To evaluate the value of cardiac magnetic resonance imaging (CMRI)-assessed left ventricular hypertrophy (LVH) in differentiating between hypertensive heart disease and hypertrophic cardiomyopathy (HCM). 95 unselected subjects with mild-to-moderate hypertension, 24 patients with HCM attributable to the D175N mutation of the ?-tropomyosin gene and 17 control subjects were studied by cine CMRI. Left ventricular (LV) quantitative and qualitative characteristics were evaluated. LV maximal end-diastolic wall thickness, wall thickness-to-LV volume ratio, end-diastolic septum thickness and septum-to-lateral wall thickness ratio were useful measures for differentiating between LVH due to hypertension and HCM. The most accurate measure for identifying patients with HCM was the LV maximal wall thickness ?17 mm, with a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 90%, 93%, 86%, 95% and 91%, respectively. LV maximal wall thickness in the anterior wall, or regional bulging in left ventricular wall was found only in patients with HCM. LV mass index was not discriminant between patients with HCM and those with LVH due to hypertension. LV maximal thickness measured by CMRI is the best anatomical parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. CMRI assessment of location and quality of LVH is also of value in differential diagnosis. (orig.)tial diagnosis. (orig.)

  16. Sensibilidade do eletrocardiograma na hipertrofia ventricular de acordo com gênero e massa cardíaca / Electrocardiogram sensitivity in left ventricular hypertrophy according to gender and cardiac mass

    Scientific Electronic Library Online (English)

    Ana P., Colossimo; Francisco de Assis, Costa; Andrés R. P., Riera; Maria T. N., Bombig; Valter C., Lima; Francisco A. H., Fonseca; Maria C. O., Izar; Bráulio, L. Filho; Dilma, Souza; Rui M. S., Povoa.

    2011-09-01

    Full Text Available FUNDAMENTO: Sabe-se que vários fatores interferem na sensibilidade do Eletrocardiograma (ECG) no diagnóstico da Hipertrofia Ventricular Esquerda (HVE), sendo o gênero e a massa cardíaca alguns dos principais. OBJETIVO: Avaliar a influência do sexo na sensibilidade de alguns dos critérios utilizados [...] para a detecção de HVE, de acordo com a progressão do grau de hipertrofia ventricular. MÉTODOS: De acordo com o gênero e com o grau de HVE ao ecocardiograma, os pacientes foram divididos em três grupos: HVE leve, moderada e severa. Avaliou-se a sensibilidade do ECG para detectar HVE entre homens e mulheres, conforme o grau de HVE. RESULTADOS: Dos 874 pacientes, 265 eram homens (30,3%) e 609, mulheres (69,7%). Os critérios [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perúgia e padrão strain mostraram alto poder discriminatório no diagnóstico de HVE entre homens e mulheres nos três grupos de HVE, com desempenho superior na população masculina e destaque para os escores [(S + R) X QRS] e Perúgia. CONCLUSÃO: A sensibilidade diagnóstica do ECG é maior com o aumento da massa cardíaca. O exame é mais sensível entre homens, destacando-se os escores [(S + R) X QRS] e Perúgia. Abstract in english BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG) sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria [...] used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3%) and 609, females (69.7%). The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R) X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.

  17. Hipertrofia ventricular e mortalidade cardiovascular em pacientes de hemodiálise de baixo nível educacional Hipertrofia ventricular y mortalidad cardiovascular en pacientes de hemodiálisis de bajo nivel educativo Ventricular hypertrophy and cardiovascular mortality in hemodialysis patients with low educational level

    Directory of Open Access Journals (Sweden)

    Rosana dos Santos e Silva Martin

    2012-01-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esquerda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguidos até outubro de 2010. Foram traçadas curvas de sobrevida comparando a mortalidade cardiovascular, e por todas as causas dos pacientes com escolaridade de até três anos (mediana da escolaridade e pacientes com escolaridade igual ou superior a quatro anos. Foram construídos modelos múltiplos de Cox ajustados para as variáveis de confusão. RESULTADOS: Observou-se associação entre nível de escolaridade e hipertrofia ventricular. A diferença estatística de mortalidade de origem cardiovascular e por todas as causas entre os diferentes níveis de escolaridade ocorreu aos cinco anos e meio de seguimento. No modelo de Cox, a hipertrofia ventricular e a proteína-C reativa associaram-se à mortalidade por todas as causas e de origem cardiovascular. A etiologia da insuficiência renal associou-se à mortalidade por todas as causas e a creatinina associou-se à mortalidade de origem cardiovascular. A associação entre escolaridade e mortalidade perdeu significância estatística no modelo ajustado. CONCLUSÃO: Os resultados do presente trabalho confirmam estudo prévio e demonstram, ademais, que a maior mortalidade cardiovascular observada nos pacientes com menor escolaridade pôde ser explicada por fatores de risco de ordem bioquímica e de morfologia cardíaca.FUNDAMENTO: La hipertrofia ventricular izquierda es potente predictor de mortalidad en renales crónicos. Estudio previo de nuestro grupo mostró que renales crónicos con menor escolaridad tienen hipertrofia ventricular más intensa. OBJETIVO: Ampliar estudio previo y verificar si la hipertrofia ventricular izquierda puede justificar la asociación entre escolaridad y mortalidad cardiovascular de pacientes en hemodiálisis. MÉTODOS: Fueron evaluados 113 pacientes entre enero de 2005 y marzo de 2008 y seguidos hasta octubre de 2010. Fueron trazadas curvas de sobrevida comparando la mortalidad cardiovascular, y por todas las causas de los pacientes con escolaridad de hasta tres años (mediana de la escolaridad y pacientes con escolaridad igual o superior a cuatro años. Fueron construidos modelos múltiples de Cox ajustados para las variables de confusión. RESULTADOS: Se observó asociación entre nivel de escolaridad e hipertrofia ventricular. La diferencia estadística de mortalidad de origen cardiovascular y por todas las causas entre los diferentes niveles de escolaridad ocurrió a los cinco años y medio de seguimiento. En el modelo de Cox, la hipertrofia ventricular y la proteína-C reactiva se asociaron a la mortalidad por todas las causas y de origen cardiovascular. La etiología de la insuficiencia renal se asoció a la mortalidad por todas las causas y la creatinina se asoció a la mortalidad de origen cardiovascular. La asociación entre escolaridad y mortalidad perdió significación estadística en el modelo ajustado. CONCLUSÓN: Los resultados del presente trabajo confirman estudio previo y demuestran, además, que la mayor mortalidad cardiovascular observada en los pacientes con menor escolaridad puede ser explicada por factores de riesgo de orden bioquímico y de morfología cardíaca.BACKGROUND: Left ventricular hypertrophy is a strong predictor of mortality in chronic kidney patients. A previous study of our group has shown that chronic kidney patients with low educational level has more severe ventricular hypertrophy. OBJECTIVE: To extend a previous study and to assess whether left ventricular hypertrophy can explain the association between schooling and cardiovascular mortality in hemodialysis patients. METHODS: This stud

  18. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    Scientific Electronic Library Online (English)

    Yu-luan, Xiang; Li, He; Jun, Xiao; Shuang, Xia; Song-bai, Deng; Yun, Xiu; Qiang, She.

    2012-03-01

    Full Text Available Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma [...] contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

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

    International Nuclear Information System (INIS)

    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 123I metaiodobenzylguanidine (MIBG) and 123I ?-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 fracecrease 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)

  20. Hipertrofia ventricular e mortalidade cardiovascular em pacientes de hemodiálise de baixo nível educacional / Ventricular hypertrophy and cardiovascular mortality in hemodialysis patients with low educational level / Hipertrofia ventricular y mortalidad cardiovascular en pacientes de hemodiálisis de bajo nivel educativo

    Scientific Electronic Library Online (English)

    Rosana dos Santos e Silva, Martin; Luis Cuadrado, Martin; Roberto Jorge da Silva, Franco; Pasqual, Barretti; Jacqueline Costa Teixeira, Caramori; João Henrique, Castro; Aline de Araújo, Antunes; Silméia Garcia, Zanati-Basan; Beatriz Bojikian, Matsubara; Antônio Sérgio, Martins.

    2012-01-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esqu [...] erda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguidos até outubro de 2010. Foram traçadas curvas de sobrevida comparando a mortalidade cardiovascular, e por todas as causas dos pacientes com escolaridade de até três anos (mediana da escolaridade) e pacientes com escolaridade igual ou superior a quatro anos. Foram construídos modelos múltiplos de Cox ajustados para as variáveis de confusão. RESULTADOS: Observou-se associação entre nível de escolaridade e hipertrofia ventricular. A diferença estatística de mortalidade de origem cardiovascular e por todas as causas entre os diferentes níveis de escolaridade ocorreu aos cinco anos e meio de seguimento. No modelo de Cox, a hipertrofia ventricular e a proteína-C reativa associaram-se à mortalidade por todas as causas e de origem cardiovascular. A etiologia da insuficiência renal associou-se à mortalidade por todas as causas e a creatinina associou-se à mortalidade de origem cardiovascular. A associação entre escolaridade e mortalidade perdeu significância estatística no modelo ajustado. CONCLUSÃO: Os resultados do presente trabalho confirmam estudo prévio e demonstram, ademais, que a maior mortalidade cardiovascular observada nos pacientes com menor escolaridade pôde ser explicada por fatores de risco de ordem bioquímica e de morfologia cardíaca. Abstract in spanish FUNDAMENTO: La hipertrofia ventricular izquierda es potente predictor de mortalidad en renales crónicos. Estudio previo de nuestro grupo mostró que renales crónicos con menor escolaridad tienen hipertrofia ventricular más intensa. OBJETIVO: Ampliar estudio previo y verificar si la hipertrofia ventri [...] cular izquierda puede justificar la asociación entre escolaridad y mortalidad cardiovascular de pacientes en hemodiálisis. MÉTODOS: Fueron evaluados 113 pacientes entre enero de 2005 y marzo de 2008 y seguidos hasta octubre de 2010. Fueron trazadas curvas de sobrevida comparando la mortalidad cardiovascular, y por todas las causas de los pacientes con escolaridad de hasta tres años (mediana de la escolaridad) y pacientes con escolaridad igual o superior a cuatro años. Fueron construidos modelos múltiples de Cox ajustados para las variables de confusión. RESULTADOS: Se observó asociación entre nivel de escolaridad e hipertrofia ventricular. La diferencia estadística de mortalidad de origen cardiovascular y por todas las causas entre los diferentes niveles de escolaridad ocurrió a los cinco años y medio de seguimiento. En el modelo de Cox, la hipertrofia ventricular y la proteína-C reactiva se asociaron a la mortalidad por todas las causas y de origen cardiovascular. La etiología de la insuficiencia renal se asoció a la mortalidad por todas las causas y la creatinina se asoció a la mortalidad de origen cardiovascular. La asociación entre escolaridad y mortalidad perdió significación estadística en el modelo ajustado. CONCLUSÓN: Los resultados del presente trabajo confirman estudio previo y demuestran, además, que la mayor mortalidad cardiovascular observada en los pacientes con menor escolaridad puede ser explicada por factores de riesgo de orden bioquímico y de morfología cardíaca. Abstract in english BACKGROUND: Left ventricular hypertrophy is a strong predictor of mortality in chronic kidney patients. A previous study of our group has shown that chronic kidney patients with low educational level has more severe ventricular hypertrophy. OBJECTIVE: To extend a previous study and to assess whether [...] left ventricular hypertrophy can explain the association between schooling and cardi

  1. Na/K Pump Current and [Na]i in Rabbit Ventricular Myocytes: Local [Na]i Depletion and Na Buffering

    OpenAIRE

    Despa, Sanda; Bers, Donald M.

    2003-01-01

    Na/K pump current (Ipump) and intracellular Na concentration ([Na]i) were measured simultaneously in voltage-clamped rabbit ventricular myocytes, under conditions where [Na]i is controlled mainly by membrane transport. Upon abrupt pump reactivation (after 10–12 min blockade), Ipump decays in two phases. Initially, Ipump declines with little [Na]i change, whereas the second phase is accompanied by [Na]i decline. Initial Ipump sag was still present at external [K] = 15 mM, but prevented by [N...

  2. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary inflammatory response, fibrin deposition and RVH, and stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic lung injury and continued during room air recovery improves alveolarization and restores pulmonary angiogenesis and RVH in experimental BPD.

  3. Diagnosis of apical hypertrophic cardiomyopathy: T-wave inversion and relative but not absolute apical left ventricular hypertrophy?

    Science.gov (United States)

    Flett, Andrew S.; Maestrini, Viviana; Milliken, Don; Fontana, Mariana; Treibel, Thomas A.; Harb, Rami; Sado, Daniel M.; Quarta, Giovanni; Herrey, Anna; Sneddon, James; Elliott, Perry; McKenna, William; Moon, James C.

    2015-01-01

    Background Diagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated. Methods We performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients. Results Of the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio > 1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2. Conclusion A cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria. PMID:25666123

  4. Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy : the Losartan Intervention For Endpoint study

    DEFF Research Database (Denmark)

    Bang, Casper N; Okin, Peter M

    2014-01-01

    BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease, in sinus rhythm on their baseline electrocardiogram. RESULTS: A total of 154 patients (2.2%) had or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients (7.1%) during a mean follow-up of 4.7 ± 1.1 years. At baseline, the psoriasis patients were younger (65 ± 7 vs. 67 ± 7 years) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage (27.6 ± 9.7 vs. 30.1 ± 10.4 mm); higher hemoglobin (6.3 ± 2.2 vs. 6.0 ± 2.7 mmol/l) and prevalence of diabetes (20.6 vs. 12.8%, P ? 0.004) than patients without psoriasis. In multivariable Cox analysis, adjusting for age, sex, hemoglobin, diabetes, time-varying SBP, heart rate, study treatment and Sokolow-Lyon hypertrophy, psoriasis, treated as a time-varying covariate, was associated with a two-fold higher risk of new-onset atrial fibrillation [hazard ratio: 1.97 (95% confidence interval (CI): 1.18-3.30), P=0.01]. Propensity-matched analysis yielded similar results (odds ratio: 3.49, 95% CI 1.24-9.81, P=0.018). CONCLUSION: Psoriasis has a similar prevalence in hypertensive patients as in the general population. Psoriasis independently predicted new-onset atrial fibrillation despite lower age and electrocardiographic LVH in psoriasis patients than in patients without psoriasis.

  5. Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes.

    Science.gov (United States)

    Simkó, József; Szentandrássy, Norbert; Harmati, Gábor; Bárándi, László; Horváth, Balázs; Magyar, János; Bányász, Tamás; Lorincz, István; Nánási, Péter P

    2010-09-01

    In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations > or = 1 microM, ropinirole increased action potential duration (APD(90)) and suppressed the rapid delayed rectifier K(+) current (I (Kr)) with an IC(50) value of 2.7 +/- 0.25 microM and Hill coefficient of 0.92 +/- 0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of I (Kr) was accelerated by 3 muM ropinirole (time constant decreased from 34 +/- 4 to 14 +/- 1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations > or = 10 microM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations > or = 30 microM), and shortened APD measured at 50% repolarization (at 300 microM) indicating a concentration-dependent inhibition of I (to), I (Na), and I (Ca). Suppression of I (Kr), I (to), and I (Ca) has been confirmed under conventional patch clamp and action potential voltage clamp conditions. I (Ks) and I (K1) were not influenced significantly by ropinirole at concentrations less than 300 microM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of I (Kr)-especially in cases of accidental overdose or intoxication. PMID:20668839

  6. Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

    Scientific Electronic Library Online (English)

    A.M., Cabral; I.F., Silva; C.R., Gardioli; H., Mauad; E.C., Vasquez.

    1998-04-01

    Full Text Available Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathe [...] tic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity

  7. Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

    Directory of Open Access Journals (Sweden)

    Cabral A.M.

    1998-01-01

    Full Text Available Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc or vehicle (soybean oil, 0.25 ml per animal was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW ratio (2.44 ± 0.09 mg/g and right ventricular weight/body weight (RVW/BW ratio (0.53 ± 0.01 mg/g compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively rats. MAP was significantly higher (39% in DOCA-salt rats. Renal denervation prevented (P>0.05 the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g and RVW/BW (0.52 ± 0.01 mg/g. We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity

  8. Resistin Promotes Cardiac Hypertrophy via the AMP-activated Protein Kinase/Mammalian Target of Rapamycin (AMPK/mTOR) and c-Jun N-terminal Kinase/Insulin Receptor Substrate 1 (JNK/IRS1) Pathways*

    OpenAIRE

    Kang, Soojeong; Chemaly, Elie R.; Roger J. Hajjar; Lebeche, Djamel

    2011-01-01

    Resistin has been suggested to be involved in the development of diabetes and insulin resistance. We recently reported that resistin is expressed in diabetic hearts and promotes cardiac hypertrophy; however, the mechanisms underlying this process are currently unknown. Therefore, we wanted to elucidate the mechanisms associated with resistin-induced cardiac hypertrophy and myocardial insulin resistance. Overexpression of resistin using adenoviral vector in neonatal rat ventricular myocytes wa...

  9. The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

    Directory of Open Access Journals (Sweden)

    T.A. Uggere

    2000-05-01

    Full Text Available Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex and chemical stimulation (chemosensitive reflex. The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45% as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.

  10. The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

    Scientific Electronic Library Online (English)

    T.A., Uggere; G.R., Abreu; K.N., Sampaio; A.M., Cabral; N.S., Bissoli.

    2000-05-01

    Full Text Available Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex) and chemical stimulation (chemosensitive reflex). The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR) and other models of hype [...] rtension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE) for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA) produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW) ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45%) as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the chemosensitive, reflex can be restored by treatment of SHR with enalapril. It is possible that by augmenting the gain of the volume-sensitive reflex control of RSNA, enalapril contributed to the reversal of cardiac hypertrophy and normalization of arterial blood pressure in SHR.

  11. Sarcolemmal ion currents and sarcoplasmic reticulum Ca2+ content in ventricular myocytes from the cold stenothermic fish, the burbot (Lota lota).

    Science.gov (United States)

    Shiels, Holly A; Paajanen, Vesa; Vornanen, Matti

    2006-08-01

    The burbot (Lota lota) is a cold stenothermic fish species whose heart is adapted to function in the cold. In this study we use whole-cell voltage-clamp techniques to characterize the electrophysiological properties of burbot ventricular myocytes and to test the hypothesis that changes in membrane currents and intracellular Ca2+ cycling associated cold-acclimation in other fish species are routine for stenothermic cold-adapted species. Experiments were performed at 4 degrees C, which is the body temperature of burbot for most of the year, and after myocytes were acutely warmed to 11 degrees C, which is in the upper range of temperatures experienced by burbot in nature. Results on K+ channels support our hypothesis as the relative density of K-channel conductances in the burbot heart are similar to those found for cold-acclimated cold-active fish species. I(K1) conductance was small (39.2+/-5.4 pS pF(-1) at 4 degrees C and 71.4+/-1.7 pS pF(-1) at 11 degrees C) and I(Kr) was large (199+/-27 pS pF(-1) at 4 degrees C and 320.3+/-8 pS pF(-1) at 11 degrees C) in burbot ventricular myocytes. We found high Na+-Ca2+ exchange (NCX) activity (35.9+/-6.3 pS pF(-1) at 4 degrees C and 58.6+/-8.4 pS pF(-1) at 11 degrees C between -40 and 20 mV), suggesting that it may be the primary pathway for sarcolemmal (SL) Ca2+ influx in this species. In contrast, the density (I(Ca), 0.81+/-0.13 pA pF(-1) at 4 degrees C, and 1.35+/-0.18 pA pF(-1) at 11 degrees C) and the charge (Q(Ca), 0.24+/-0.043 pC pF(-1) at 4 degrees C and 0.21+/-0.034 pC pF(-1) at 11 degrees C) carried by the L-type Ca2+ current was small. Our results on sarcolemmal ion currents in burbot ventricular myocytes suggest that cold stenothermy and compensative cold-acclimation involve many of the same subcellular adaptations that culminate in enhanced excitability in the cold. PMID:16888058

  12. 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)

  13. Usefulness of QRS voltage correction by body mass index to improve electrocardiographic detection of left ventricular hypertrophy in patients with systemic hypertension.

    Science.gov (United States)

    Angeli, Fabio; Verdecchia, Paolo; Iacobellis, Gianluca; Reboldi, Gianpaolo

    2014-08-01

    Obesity reduces the accuracy of voltage-based electrocardiographic (ECG) criteria for diagnosis of left ventricular (LV) hypertrophy. We developed a new ECG score for diagnosis of LV hypertrophy, defined either by a typical strain pattern or a product of the Cornell voltage (R wave height in lead aVL plus S wave depth in lead V3) by body mass index >604 mm?kg/m(2). We examined a population of 2,747 untreated hypertensive subjects (mean age 49 ± 11 years) with good quality ECG and echocardiographic tracings. Several traditional ECG criteria for LV hypertrophy were compared with the new score, with echocardiographic LV mass taken as reference. Among the tested criteria, the highest sensitivity combined with specificity was yielded by the new score (sensitivity 36.1%, 95% confidence interval [CI] 32.9 to 39.4; specificity 90.5%, 95% CI 89.1 to 91.8; and accuracy 73.1%, 95% CI 71.5 to 74.8). Prevalence of ECG LV hypertrophy with the new score was 18%. On the basis of comparisons between areas under the receiver operating characteristic curves, the best performance was achieved by the new score with respect to other ECG criteria for LV hypertrophy (all p <0.0001). In conclusion, correction of Cornell voltage by body mass index as a marker of obesity improves the performance of traditional electrocardiography for diagnosis of LV hypertrophy in patients with hypertension. PMID:24934758

  14. Avaliação da redução de gradientes pressóricos e da hipertrofia ventricular após valvoplastia cirúrgica na estenose aórtica / Left ventricular hypertrophy regression immediately after aortic valve repair

    Scientific Electronic Library Online (English)

    G. R., Hoppen; R. A.K., Kalil; F. B., Ludwig; A., D' Avila.

    2000-10-01

    Full Text Available INTRODUÇÃO: A correção cirúrgica da estenose aórtica resulta em redução significativa do gradiente pressórico transvalvar, sendo acompanhada por regressão da hipertrofia ventricular esquerda(HVE). A intensidade e a rapidez dessa regressão tem sido objeto de avaliações. A associação de valvoplastia a [...] órtica e regressão imediata da HVE é relatada em poucos estudos. MÉTODOS: Foram estudados, prospectivamente, 11 pacientes submetidos à valvoplastia em estenose aórtica, utilizando-se ecocardiografia imediatamente antes da cirurgia e no período pós-operatório precoce (6,1±0,9 dias). RESULTADOS: A espessura septal variou de 12,10±1,66mm para 11,36±1,12mm (redução de 6,1%) (NS) enquanto a espessura parietal variou 4,4% (de 11,70±1,41 mm para 11,18±1,16mm) (NS). A fração de ejeção apresentou uma variação de 62,02± 18,59% para 62,50±11,74% (NS). A massa ventricular esquerda variou em 6,7% ( de 277,65±114,80 g passou para 258,93±92,38 g) (NS). O gradiente transvalvular médio regrediu de 53,6±10,3 mmHg para 23,0±9,1mmHg, ou seja, 57% (p Abstract in english BACKGROUND: Relief of gradient is followed by myocardial mass reduction in aortic stenosis. Its degree and speed are under evaluation. Aortic valve repair in calcified aortic stenosis is less well studied than replacement. METHODS: We evaluated left ventricular hypertrophy reduction by echocardiogra [...] m in 11 patients immediately after valve repair in aortic stenosis at a mean of 6.1 ± 0.9 days post operative. RESULTS: Septal width was 12.10 ± 1.66 mm pre and 11.36 ± 1.12 mm post operative, 6,1% reduction (NS). Parietal width varied 4.4% from 11.70±1.41 mm to 11.18 ± 1,16 mm (NS). Ejection fraction went from 62.02±18.59% to 62.50±11. 74% (NS). Left ventricular mass varied 6.7%, from 277.65±114.80g to 258.93± 92.38 g (NS). Mean transvalvar gradient reduced 57%, from 53.56±10.30 to 23.0±9.1 mmHg (P

  15. Towards a re-definition of 'cardiac hypertrophy' through a rational characterization of left ventricular phenotypes: a position paper of the Working Group 'Myocardial Function' of the ESC.

    Science.gov (United States)

    Knöll, Ralph; Iaccarino, Guido; Tarone, Guido; Hilfiker-Kleiner, Denise; Bauersachs, Johann; Leite-Moreira, Adelino F; Sugden, Peter H; Balligand, Jean-Luc

    2011-08-01

    Many primary or secondary diseases of the myocardium are accompanied with complex remodelling of the cardiac tissue that results in increased heart mass, often identified as cardiac 'hypertrophy'. Although there have been numerous attempts at defining such 'hypertrophy', the present paper delineates the reasons as to why current definitions of cardiac hypertrophy remain unsatisfying. Based on a brief review of the underlying pathophysiology and tissue and cellular events driving myocardial remodelling with or without changes in heart dimensions, as well as current techniques to detect such changes, we propose to restrict the use of the currently popular term 'hypertrophy' to cardiac myocytes that may or may not accompany the more complex tissue rearrangements leading to changes in shape or size of the ventricles, more broadly referred to as 'remodelling'. We also discuss the great potential of genetically modified (mouse) models as tools to define the molecular pathways leading to the different forms of left ventricle remodelling. Finally, we present an algorithm for the stepwise assessment of myocardial phenotypes applicable to animal models using well-established imaging techniques and propose a list of parameters most suited for a critical evaluation of such pathophysiological phenomena in mouse models. We believe that this effort is the first step towards a much auspicated unification of the terminology between the experimental and the clinical cardiologists. PMID:21708908

  16. Obesidad central y regresión de hipertrofia ventricular izquierda / Central obesity and left ventricular hypertrophy regression / Obesidade central e regressão da hipertrofia esquerda

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Luciano, Citta; Norberto, Citta; Marcelo, Lanzotti; Roberto, Lanzotti; Horacio, Locatelli; Alicia, Tommasi.

    2007-12-01

    Full Text Available Em sujeitos hipertensos, os níveis de pressão arterial per se seriam a principal determinante do desenvolvimento de hiperetrofia ventricular esquerda. Por outra parte, o índice de massa corporal e o perímetro de cintura se associaram em forma lineal, contínua e positiva com o índice de massa ventric [...] ular esquerdo ainda em não hipertensos. Um tratamento insuficiente seria a principal causa da falta de regressão do dano no órgão branco. O objetivo do presente trabalho é determinar o impacto da obesidade central sobre a regressão do índice de massa ventricular esquerdo. Material e métodos: incluíram-se 102 pacientes (p) HTA que concorreram por primeira vez a um consultório especializado em forma consecutiva, mediulhes o índice de massa ventricular esquerdo (IMVE) pelo método de Devereux ao início e logo de pelo menos 1 ano de tratamento. Foram divididos em dois grupos: GA: perímetro cintura (PC) esses valores. Para a análise de estatística se aplicou test t de Students para diferenças de médias e proporções, e se considerou significação estatístico p Abstract in spanish En sujetos hipertensos, los niveles de presión arterial per se serían el principal determinante del desarrollo de hipertrofia ventricular izquierda. Por otra parte, el índice de masa corporal y el perímetro de cintura se han asociado en forma lineal, continua y positiva con elíndice de masa ventricu [...] lar izquierdo aún en no hipertensos. Un tratamiento insuficiente sería la principal causa de falta de regresión del daño en órgano blanco. El objetivo del presente trabajo es determinar el impacto de la obesidad central sobre la regresión del índice de masa ventricular izquierdo. Material y métodos: se incluyeron 102 pacientes (p) HTA que concurrieron por primera vez a un consultorio especializado en forma consecutiva, se les midió el índice de masa ventricular izquierdo (IMVI) por método de Devereux al inicio y luego de al menos 1 año de tratamiento. Fueron divididos en dos grupos: GA: perímetro cintura (PC) esos valores. Para el análisis estadístico se aplicó test t de Students para diferencias de medias y proporciones, y se consideró significación estadística p Abstract in english Blood pressure per se may be the main determinant of left ventricle hypertrophy development in hypertensive subjects. On the other side, body mass index and waist circumference are related to left ventricle mass index (LVMI) positively, continuously and linearly even in non hypertensive patients. An [...] insufficient treatment may be the main reason of not achieving regression of target organ damage. The objective of this trial is to establish the impact of central obesity on LVMI regression. Material and methods: 102 consecutive hypertensive patients (p) wich attended for the first time to a specialized consultory room were included. LVMI was measured with the Devereux method at the begining and after at least one year of treatment. The patients were divided into two groups: GA: waist circumference (WC) of those values. The statistic analysis was done with the Students t test for differences in proportions and means and a p value

  17. The Effects of Cyclic Guanylate Cyclase Stimulation on Right Ventricular Hypertrophy and Failure Alone and in Combination with Phosphodiesterase-5 Inhibition

    DEFF Research Database (Denmark)

    Andersen, Asger; Nielsen, Jan MØller

    2013-01-01

    BACKGROUND:: We investigated if soluble guanylate cyclase stimulation either alone or in combination with PDE5 inhibition could prevent pressure overload induced right ventricular hypertrophy and failure. METHODS AND RESULTS:: The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg/kg/day) either alone or in combination (BAY+SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg/kg/day) was examined for prevention of right ventricular hypertrophy and failure in Wistar rats (n=73) operated by pulmonary trunk banding (PTB).All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY+SIL groups there were an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY+SIL group. Systolic RV pressure was increased in the BAY and BAY+SIL group possibly due to an inotropic response and/or increased venous return. CONCLUSIONS:: Stimulation of sGC by BAY 41-2272 alone or in combination with sildenafil failed to prevent the developmentof RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.

  18. Prevalence, pattern, and functional impact of late gadolinium enhancement in left ventricular hypertrophy due to aortic valve stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Nassenstein, K.; Schlosser, T. [Universitaetsklinikum Essen (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Bruder, O. [Elisabeth-Krankenhaus Essen (Germany). Klinik fuer Kardiologie und Angiologie; Breuckmann, F.; Erbel, R. [Universitaetsklinikum Essen (Germany). Westdeutsches Herzzentrum Essen; Barkhausen, J. [Universitaetsklinikum Schleswig-Holstein, Luebeck (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2009-05-15

    Purpose: To assess the prevalence and pattern of myocardial late gadolinium enhancement (LGE) and its functional impact on patients with left ventricular hypertrophy caused by aortic valve stenosis. Materials and Methods: Cardiac magnetic resonance imaging of 40 patients (17 female, 23 male, mean age: 76.6 {+-} 22.5 years) with known aortic valve stenosis (mean aortic valve area: 89.8 {+-} 19.2 mm{sup 2}) and without coronary artery disease was performed at 1.5 T using steady-state free precession sequences for aortic valve planimetry and for the assessment of left ventricular (LV) volumes and mass. Ten to 15 minutes after injection of 0.2 mmol Gd-DTPA per kilogram body weight, inversion-recovery prepared spoiled gradient echo images were acquired in standard long and short axis views to detect areas of LGE. Results: LGE was observed in 32.5 % (13/40) of our patients. LGE was mainly located in the basal septal and inferior LV segments, and showed a non-ischemic pattern with sparing of the subendocardial region. Patients with LGE showed lower LV ejection fractions (55.5 {+-} 13.8 % vs. 69.1 {+-} 10.7 %, p = 0.0014), higher LV end-systolic volumes (59.8 {+-} 33.3 ml vs. 36.6 {+-} 16.0 ml, p = 0.0048), and LV masses (211.0 {+-} 13.8 vs. 157.9 {+-} 37.5 g, p = 0.0002) compared to patients without LGE. (orig.)

  19. Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease

    International Nuclear Information System (INIS)

    Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary ive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects

  20. A comparative study of urine albumin ratio to creatinine in hypertensivepatients with or without left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    M. Ansari

    2006-01-01

    Full Text Available Background and purpose: Echocardiography and routine E.C.G are standard methods for left ventricular hypertrophy (LVH. However, urine albumin to creatinine ratio (UACR recommended by recent investigations is more available and less expensive than echocardiography for detection of LVH.Materials and Methods: According to inclusion and exclusion criteria, 124 hypertensive patients (62 cases with LVH and 62 cases without LVH were selected and divided into two groups. Eechocardiography and routine E.C.G were done for all patients. Urine albumin (nephlometric methods and creatinine were measured and in patients with urine albumin>100mg/dl, ACR was calculated.Results: No significant differences were observed in mean B.U.N and creatinine, FBS and BMI between two groups. The comparison of UACR between two groups indicates that the frequency of patients with UACR> 100 mg/g in group with LVH, was more than the group without LVH (sensitivity 32.5% and specificity 92%. By combination of these tests a higher sensitivity was obtained (with Cornell criteria 37.1%.Thus, if UACR > 100 is combined with one of the markers of E.C.G for LVH diagnosis, more cases would be detected.Conclusion: Albumin to creatinine ratio in a randomized urine sample, in hypertensive patients. with LVH is higher than patients without LVH and UACR>100 can be applied for diagnosis of LVH More over by combination of E.C.G to ACR a higher sensitivity would be obtained.

  1. Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Fyhrquist, Frej; Eriksson, Anders

    2013-01-01

    INTRODUCTION: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. METHODS: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I/D genotype with LTL and cardiovascular risk. RESULTS: Mean LTL in DD or ID genotype was shorter (8.15 and 8.14 kb, respectively), than in II genotype (8.27 kb, p=0.0005). This difference was significant in the younger subjects (55-64 years, p=0.02) but not in the older group (65-80 years, p=0.56 ). In DD but not I/D or II genotype, proportion of short telomeres (

  2. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

    International Nuclear Information System (INIS)

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min-1 g-1; P-1 g-1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH. (orig.)

  3. Sensitivity and specificity of frequently used electrocardiographic criteria for left ventricular hypertrophy in patients with anterior wall myocardial infarction

    Science.gov (United States)

    Glancy, D. Luke; Oral, Evrim

    2010-01-01

    Electrocardiographic left ventricular hypertrophy (LVH) strongly predicts mortality in patients with myocardial infarction (MI). However, the validity of LVH voltage criteria in this context has not been assessed. Reviewing the coded database of echocardiographic studies performed at one institution, we performed a retrospective analysis of 49 patients who had anterior akinesis on the echocardiogram and anterior wall MI on the electrocardiogram. Results showed that, compared with the sensitivities and specificities of the electrocardiographic voltage criteria in historical cohorts, Cornell criteria were less sensitive and specific for the diagnosis of LVH in patients with anterior wall MI. The sensitivity was reduced in the presence of an associated lateral wall MI, and the specificity was reduced in the absence of a lateral wall MI (overall sensitivity in case of anterior wall MI, with or without an associated lateral wall MI, 21% vs 41%, P = 0.049; overall specificity 84% vs 98%, P = 0.003). All criteria, except for S in V1 + R in V5 or V6 >3.5 mV, had a significantly reduced specificity in the case of anterior wall MI not associated with lateral wall MI, and all criteria, except for R in V6 > R in V5, had reduced sensitivity in the presence of a lateral wall MI. In conclusion, anterior wall MI reduces the sensitivity and the specificity of the most commonly used LVH voltage criteria. PMID:20157497

  4. La hipertrofia ventricular izquierda no siempre revierte con el descenso de la presión arterial / Left ventricular hypertrophy not always reverts with the decrease in blood pressure / A hipertrofia ventricular esquerda nem sempre reverte com a diminuição da pressão arterial

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Alicia, Tommasi.

    2010-03-01

    Full Text Available Introdução. Em pacientes hipertensos considera-se que uma queda nos valores da pressão arterial é necessária para atingir a regressão da lesão em órgãos-alvo. O objetivo deste estudo é determinar o efeito obtido com a diminuição da pressão arterial em pacientes hipertensos arteriais na hipertrofia v [...] entricular esquerda em uma clínica especializada. Material e métodos. Os pacientes hipertensos na primeira consulta, segundo definição da IV Guias da Federação Argentina de Cardiologia, com hipertrofia ventricular esquerda diagnosticada pelo método ecocardiográfico de Devereux, considerando sua presença com um índice de massa ventricular esquerda igual ou superior a 110 g/m² em mulheres e 125 g/m², em homens, divididos em dois grupos: 1) a pressão arterial controlada: menos de 140 - 90 mm Hg ou inferior a 130 - 80 mm Hg em pacientes de alto risco, os pacientes com nefropatia diabética ou portadores de doença isquêmica do coração no final do seguimento, 2) pressão arterial não controlada: acima dos valores estabelecidos no final do seguimento. Aplicou-se na análise estadística o teste t de Student, considerando-se significância estatística p Abstract in spanish Introducción. En pacientes hipertensos se considera que el descenso de las cifras de presión arterial logra la regresión del daño en órgano blanco. El objetivo del presente estudio es determinar el efecto que se obtiene con el descenso de la presión arterial en pacientes hipertensos arteriales sobre [...] la hipertrofia ventricular izquierda en un consultorio especializado. Material y métodos. Pacientes hipertensos en primera consulta según definición de las IV Guías de la Federación Argentina de Cardiología, con hipertrofia ventricular izquierda diagnosticada en ecocardiografía por método de Devereux, considerándose su presencia con un índice de masa ventricular izquierda mayor o igual a 110 gramos/m² en las mujeres y 125 gramos/m² en los hombres; divididos en dos grupos: 1) presión arterial controlada: menor a 140-90 mm Hg o menor a 130-80 mm Hg en pacientes de alto riesgo, diabéticos, nefrópatas o portadores de cardiopatía isquémica al final del seguimiento; 2) presión arterial no controlada: por encima de las cifras enunciadas al final del seguimiento. En el análisis estadístico, se aplicó test t de students, considerándose significación estadística p Abstract in english Background. In hypertensive patients it is considered that a fall in blood pressure values is necessary to achieve the regression of target organ damage. The aim of this study is to determine the effect obtained with decreasing blood pressure in hypertensive patients on left ventricular hypertrophy [...] in a specialized clinic. Methods. Hypertensive patients at first consultation as defined by Argentina Cardiology Federation Guides IV, with left ventricular hypertrophy diagnosed by echocardiographic method of Devereux, considering its presence with a left ventricular mass index equal or greater than 110 g/m² in women and 125 g/m² in men, divided into two groups: 1) controlled blood pressure: less than 140 - 90 mm Hg or lower than 130 - 80 mm Hg in high risk patients, patients with diabetic nephropathy or ischemic heart disease carriers at end of follow up, 2) uncontrolled blood pressure: above the values set out at the end of follow up. In statistical analysis t students test was applied, considering statistical significance p

  5. Relationship of left ventricular systolic function to persistence or development of electrocardiographic left ventricular hypertrophy in hypertensive patients : implications for the development of new heart failure

    DEFF Research Database (Denmark)

    Okin, Peter M; Wachtell, Kristian

    2014-01-01

    BACKGROUND: Persistence or development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria is associated with an increased risk of developing heart failure compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via worse left ventricular systolic function in patients with new or persistent ECG LVH. METHODS: Baseline and year-3 ECG LVH and left ventricular midwall shortening (MWS) were examined in 725 hypertensive patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Sex-specific criteria were used for abnormal MWS (<14% in men and <16% in women) and abnormal stress-corrected MWS (scMWS; <87% in men and <90% in women). Cornell product LVH greater than 2440?mm ms defined ECG LVH. RESULTS: Between baseline and year-3 follow-up, there was continued absence or regression of ECG LVH in 427 patients and persistence or development of new LVH in 298 patients. At baseline, although there were no significant differences in the mean values of MWS and scMWS, patients with persistence or development of ECG LVH at year 3 had significantly higher baseline prevalences of abnormal MWS (41.9 vs. 30.2%, P?=?0.001) and abnormal scMWS (27.4 vs. 20.5%, P?=?0.034). At year-3 follow-up, persistence or development of new LVH was associated with significantly lower mean MWS (16.5?±?2.3 vs. 17.2?±?1.9%, P?ventricular systolic dysfunction after 3 years' follow-up. These findings provide insight into a possible mechanism by which changes in ECG LVH are associated with the changing risk of developing heart failure. CLINICAL TRIALS REGISTRATION: http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

  6. The influence of cell dimensions on the vulnerability of ventricular myocytes to lethal injury by high-intensity electrical fields / Influência das dimensões celulares sobre a vulnerabilidade de miócitos ventriculares ao efeito letal de campos elétricos de alta intensidade

    Scientific Electronic Library Online (English)

    Jair Trapé, Goulart; Pedro Xavier de, Oliveira; José Wilson Magalhães, Bassani; Rosana Almada, Bassani.

    2012-12-01

    Full Text Available Campos elétricos de alta intensidade (HIEF) são aplicados ao miocárdio durante desfibrilação e cardioversão. Embora eficazes na reversão de arritmias potencialmente letais, HIEF podem lesar cardiomiócitos por eletropermeabilização da membrana. Neste estudo, a influência das dimensões celulares sobre [...] o efeito letal de HIEF foi estudada em cardiomiócitos isolados de rato alinhados paralelamente ao campo. A máxima variação do potencial de membrana induzida pelo campo (?Vmax) foi calculada com o modelo de Klee-Plonsey. As células estudadas foram distribuídas em dois pares de grupos de acordo com seu comprimento e largura. A intensidade limiar do campo não dependeu da largura celular, mas sim do comprimento (menor nas células mais longas, p Abstract in english Application of high intensity electric fields (HIEF) to the myocardium is commonly used for cardiac defibrillation/cardioversion. Although effective at reversing life-threatening arrhythmias, HIEF may cause myocyte damage due to membrane electropermeabilization. In this study, the influence of cell [...] length and width on HIEF-induced lethal injury was analyzed in isolated rat cardiomyocytes in parallel alignment with the field. The field-induced maximum variation of membrane potential (?Vmax) was estimated with the Klee-Plonsey model. The studied myocyte population was arranged in two group pairs for comparison: the longest vs. the shortest cells, and the widest vs. narrowest cells. Threshold field intensity was significantly lower in the longest vs. shortest myocytes, whereas cell width influence was not significant. The threshold ?Vmax was comparable in all groups. Likewise, a significant leftward shift of the lethality curve (i.e., relationship of the probability of lethality vs. field intensity) of the longest cells was observed, evidencing greater sensitivity to HIEF-induced damage. However, the lethality curve as a function of ?Vmax was similar in all groups, confirming a prediction of the Klee-Plonsey model. The similar results for excitation and injury at threshold and HIEF stimulation, respectively, indicate that: a) the effect of cell length on the sensitivity to the field would be attributable to differences in field-induced membrane polarization that lead to excitation or lethal electroporation; b) the Klee-Plonsey model seems to be reliable for analysis of cell interaction with HIEF; c) it is possible that increased cell length in hypertrophied hearts enhances myocyte fragility upon defibrillation/cardioversion.

  7. 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

    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 patients aged 54–83 years with systolic blood pressure (BP) of 160–200¿mm¿Hg, diastolic BP <90¿mm¿Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow–Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow–Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75–0.92, P=0.001 per 1050¿mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65–0.87, P<0.001 per 10.5¿mm (1 s.d.) lower Sokolow–Lyon voltage). In parallel analyses, lower Cornell product and Sokolow–Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow–Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow–Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.

  8. Effects of valsartan and nebivolol on blood pressure, QT dispersion and left ventricular hypertrophy in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Luminita L??ea

    2010-06-01

    Full Text Available Objectives: The aim of this study was to analyze the antihypertensiveeffect of Valsartan and Nebivolol and their effects on QT dispersion and left ventricular hypertrophy (LVH in the treatment of naive hypertensive patients.Methods: A prospective study with a six-month follow-up was conducted on hypertensive patients with LVH and mild/ moderate essential hypertension. The patients were randomly assigned to Valsartan (80 to 160 mg/day or Nebivolol (5 to 10 mg/day groups. The study group consistedof 108 patients, 55 in the Valsartan group and 53 in the Nebivolol group.Results: The range of mean systolic blood pressure (SBP varied from 152±17 (baseline to 132±17 mmHg (follow-up in the Valsartan group (p<0.001; from 146±13 to 125±14 mmHg in the Nebivolol group (p<0.001. The decrease in mean diastolic blood pressure (DBP was 9.5±2.5 mmHg in the Valsartan group and 12.3±5.0 mmHg in the Nebivolol group. A significant reduction in QT and corrected QT (Bazett’s formula dispersion was observed in both groups, with a slightly higher reduction in the Valsartan group. Echocardiography showed a decreasein the left ventricle mass (LVM indices (p<0.05 in both groups with a greater reduction in the Valsartan group.Conclusion: Valsartan treatment was as effective as Nebivolol in reducing the 24 hour- SBP after a 6 month treatment. Nebivolol treatment proved to be superior to Valsartan in reducing DBP. Both therapies were effective in reducing the LVH; Valsartan proved to be superior to Nebivolol in reducing the QT interval indexes in relation to blood pressure and LVM reduction.

  9. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy: a case-control study.

    Science.gov (United States)

    Nielsen, M L; Pareek, M; Gerke, O; Diederichsen, S Z; Greve, S V; Blicher, M K; Sand, N P R; Mickley, H; Diederichsen, A C P; Olsen, M H

    2015-05-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P = 0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P = 0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P < 0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present. PMID:25273860

  10. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy : a case-control study

    DEFF Research Database (Denmark)

    Nielsen, M L; Pareek, Manan

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present.Journal of Human Hypertension advance online publication, 2 October 2014; doi:10.1038/jhh.2014.88.

  11. The occurrence of left ventricular hypertrophy in normotensive individuals in a community setting in North-East Trinidad

    Directory of Open Access Journals (Sweden)

    Bacchus R

    2011-07-01

    Full Text Available Romel Bacchus, Kristianna Singh, Ijaz Ogeer, Kameel MungrueDepartment Paraclinical Sciences, Public Health and Primary Care Unit, Faculty of Medical Sciences, University of the West Indies, EWMSC, Mt Hope TrinidadObjective: The purpose of this study is to determine primarily the occurrence of left ventricular hypertrophy (LVH in normotensive Trinidadians.Design and methods: Enrolment into the study required participants to have normal blood pressure (?140/90 using the JNC 7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification, free of type 2 diabetes, as well as no existing LVH. Upon entry into the study, participants were first screened for LVH using a standard 12-lead electrocardiogram (ECG, using the Sokolow–Lyon index and the Cornell index. ECHO was used to confirm or refute the diagnosis of LVH.Results: A total of 209 patients met the criteria for entry into the study. Of these, 63.6% had LVH using Cornell criteria and 68.2% using LVH by Sokolow–Lyon criteria. Subsequently, ECHO confirmed the diagnosis in 2.9% using American Society of Echocardiography criteria and 1.5% using World Health Organization criteria. Thus the estimated prevalence of LVH in normotensive individuals was approximately 3%.Conclusion: The estimated prevalence of LVH in normotensive individuals appears to be relatively high if an ECG is the single investigation performed, which is common in our setting and may also be common in the developing world. However, using ECHO, the prevalence of LVH approaches a value similarly reported in the literature. Therefore, these findings raise two important issues: 1 the use of criteria such as the Cornell and Sokolow–Lyon voltage criteria established in the developed world from populations of vastly different ethnic backgrounds may not be widely applicable, and 2 all individuals suspected of having LVH should have an ECHO.Keywords: hypertension, normotensive, echocardiography, Sokolow–Lyon

  12. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Birger; Meyer, Christian; Hove, Jens D.; Holm, Soeren; Kofoed, Klaus F. [Department of Clinical Physiology and Nuclear Medicine, KF 4011, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen (Denmark); Nielsen, Flemming S.; Sato, Asako; Parving, Hans-Henrik [Steno Diabetes Center, Gentofte (Denmark); Bang, Lia E.; Svendsen, Tage L. [Department of Internal Medicine, Naestved County Hospital (Denmark); Opie, Lionel H. [Department of Medicine, Cape Heart Center, University of Cape Town (South Africa)

    2004-03-01

    The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123{+-}7/65{+-}9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8{+-}0.6 vs 2.5{+-}1.0 ml min{sup -1} g{sup -1}; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7{+-}1.0 vs 3.6{+-}1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9{+-}0.9 (P<0.001) due to normalisation of maximal perfusion (2.3{+-}0.5 ml min{sup -1} g{sup -1}, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH. (orig.)

  13. Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração Left ventricular hypertrophy of athletes: adaptative physiologic response of the heart

    Directory of Open Access Journals (Sweden)

    Nabil Ghorayeb

    2005-09-01

    Full Text Available OBJETIVO: Verificar se a hipertrofia ventricular esquerda (HVE de atletas competitivos de resistência (maratonistas representa processo adaptativo, puramente fisiológico, ou se pode envolver aspectos patológicos em suas características anatômicas e funcionais. MÉTODOS: De novembro de 1999 a dezembro de 2000, foram separados consecutivamente de 30 maratonistas em atividade esportiva plena, idade inferior a 50 anos, com HVE, previamente documentada, e sem cardiopatia subjacente. Foram submetidos aos exames: clínico, eletrocardiograma, ecodopplercardiograma, e teste ergométrico (TE. Quinze foram sorteados para realizar, também, teste ergoespirométrico e ressonância magnética (RM do coração. RESULTADOS: Nos TE, todos apresentavam boa capacidade física cardiopulmonar, sem evidências de resposta isquêmica ao exercício, sintomas ou arritmias. No ecodopplercardiograma, os valores do diâmetro e espessura diastólica da parede posterior do ventrículo esquerdo (VE, do septo interventricular, massa do VE e diâmetro do átrio esquerdo, foram significativamente maiores que os do grupo de não atletas, com idades e medidas antropométricas semelhantes. A média da massa do VE dos atletas indexada à superfície corpórea (126 g/m2 foi significativamente maior que a do grupo controle (70 g/m2 (pOBJECTIVE: To verify whether left ventricular hypertrophy (LVH of elite competition athletes (marathoners represents a purely physiological, adaptative process, or it may involve pathological aspects in its anatomical and functional characteristics. METHODS: From November 1999 to December 2000, consecutive samples from 30 under 50-year-old marathoners in full sportive activity, with previously documented LVH and absence of cardiopathy were selected. They were submitted to clinical exams, electrocardiogram, color Doppler echocardiogram and exercise treadmill test (ETT. Fifteen were assorted to be also submitted to ergoespirometric test and heart magnetic resonance imaging (MRI. RESULTS: In ETT, all of them showed good physical pulmonary capacity, with no evidences of ischemic response to exercise, symptoms or arrhythmias. In Doppler echocardiogram, values of diameter and diastolic thickness of LV posterior wall, interventricular septum, LV mass and left atrium diameter, were significantly higher when compared to non-athlete control group, with similar ages and anthropometric measurements. The mean of LV mass of athletes indexed to body surface (126 g/m2 was significantly greater than the one in control group (70 g/m2 (p<0.001. Magnetic resonance imaging (MRI showed there was not impairment of contractile strength or LV performance, and values of end diastolic volume, end systolic volume and EF within limits of normality. On the other hand, average ventricular parietal mass, 162.93±17.90 g, and LV parietal thickness, 13.67±2.13 mm, at the end of diastole in athlete group, differed significantly from control group: 110±14.2 g (p=0.0001 and 8±0.9 mm, respectively (p=0.0001. The same happened to the thickness at the end of systole, which was 18.87±3.40 mm (control group: 10±1.80 mm, p=0.0001. CONCLUSION: Results allowed for concluding that LVH in marathoners in full sportive activity period, assessed by non-invasive methods, represents an adaptative response to intensive and prolonged physical training, with purely physiological characteristics.

  14. Inhibition of the isoproterenol-induced net 45Ca uptake into the total heart of the rat in left ventricular hypertrophy due to aortic constriction

    International Nuclear Information System (INIS)

    The increase of the transmembranary Ca++ inflow is the decisive initial reaction for the cardio-action of ?-adrenergic catecholamines. For example, a single subcutaneous application of 1 mg isoproterenol/kg increases the net 45Ca uptake into the rat heart to 3 or 4 times the normal value. With experimentally induced left ventricular hypertrophy, however, the ?-adrenergic reactivity of the whole rat heart decreases substantially about three weeks after the coarctation of the aorta. This is indicated by the strong inhibition of the net 45Ca uptake by the myocardium under the influence of isoproterenol, not only in the hypertrophic left ventricle but also in the non-hypertrophic right ventricle. The reduction of the ?-adrenergic stimulation is thus not a direct effect of fibrons hypertrophy but rather a more general side-effect which may be due to a lasting increase in the sympathicotonus under stress. (orig./AK)

  15. Relationship between intracellular pH and proton mobility in rat and guinea-pig ventricular myocytes.

    OpenAIRE

    Swietach, P.; Vaughan-jones, Rd

    2005-01-01

    Intracellular H+ ion mobility in eukaryotic cells is low because of intracellular buffering. We have investigated whether Hi+ mobility varies with pHi. A dual microperfusion apparatus was used to expose guinea-pig or rat myocytes to small localized doses (3-5 mm) of ammonium chloride (applied in Hepes-buffered solution). Intracellular pH (pHi) was monitored confocally using the fluorescent dye, carboxy-SNARF-1. Local ammonium exposure produced a stable, longitudinal pHi gradient. Its size was...

  16. Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release.

    Science.gov (United States)

    Wang, Xiao; Weinberg, Seth H; Hao, Yan; Sobie, Eric A; Smith, Gregory D

    2015-03-01

    Population density approaches to modeling local control of Ca(2+)-induced Ca(2+) release in cardiac myocytes can be used to construct minimal whole cell models that accurately represent heterogeneous local Ca(2+) signals. Unfortunately, the computational complexity of such "local/global" whole cell models scales with the number of Ca(2+) release unit (CaRU) states, which is a rapidly increasing function of the number of ryanodine receptors (RyRs) per CaRU. Here we present an alternative approach based on a Langevin description of the collective gating of RyRs coupled by local Ca(2+) concentration ([Ca(2+)]). The computational efficiency of this approach no longer depends on the number of RyRs per CaRU. When the RyR model is minimal, Langevin equations may be replaced by a single Fokker-Planck equation, yielding an extremely compact and efficient local/global whole cell model that reproduces and helps interpret recent experiments that investigate Ca(2+) homeostasis in permeabilized ventricular myocytes. Our calculations show that elevated myoplasmic [Ca(2+)] promotes elevated network sarcoplasmic reticulum (SR) [Ca(2+)] via SR Ca(2+)-ATPase-mediated Ca(2+) uptake. However, elevated myoplasmic [Ca(2+)] may also activate RyRs and promote stochastic SR Ca(2+) release, which can in turn decrease SR [Ca(2+)]. Increasing myoplasmic [Ca(2+)] results in an exponential increase in spark-mediated release and a linear increase in nonspark-mediated release, consistent with recent experiments. The model exhibits two steady-state release fluxes for the same network SR [Ca(2+)] depending on whether myoplasmic [Ca(2+)] is low or high. In the later case, spontaneous release decreases SR [Ca(2+)] in a manner that maintains robust Ca(2+) sparks. PMID:25485896

  17. Identification of caveolar resident proteins in ventricular myocytes using a quantitative proteomic approach: dynamic changes in caveolar composition following adrenoceptor activation.

    Science.gov (United States)

    Wypijewski, Krzysztof J; Tinti, Michele; Chen, Wenzhang; Lamont, Douglas; Ashford, Michael L J; Calaghan, Sarah C; Fuller, William

    2015-03-01

    The lipid raft concept proposes that membrane environments enriched in cholesterol and sphingolipids cluster certain proteins and form platforms to integrate cell signaling. In cardiac muscle, caveolae concentrate signaling molecules and ion transporters, and play a vital role in adrenergic regulation of excitation-contraction coupling, and consequently cardiac contractility. Proteomic analysis of cardiac caveolae is hampered by the presence of contaminants that have sometimes, erroneously, been proposed to be resident in these domains. Here we present the first unbiased analysis of the proteome of cardiac caveolae, and investigate dynamic changes in their protein constituents following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated with methyl-?-cyclodextrin (M?CD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from M?CD-treated and control cell lysates using a standard discontinuous sucrose gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated, digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were consistently depleted from the BCEM fraction following M?CD treatment. Selective activation of ?-, ?1-, and ?2-AR prior to preparation of BCEMs was achieved by application of agonist/antagonist pairs for 10 min in populations of field-stimulated myocytes. We typically identified 600-850 proteins per experiment, of which, 249 were defined as high-confidence BCEM residents. Functional annotation clustering indicates cardiac BCEMs are enriched in integrin signaling, guanine nucleotide binding, ion transport, and insulin signaling clusters. Proteins possessing a caveolin binding motif were poorly enriched in BCEMs, suggesting this is not the only mechanism that targets proteins to caveolae. With the notable exception of the cavin family, very few proteins show altered abundance in BCEMs following AR activation, suggesting signaling complexes are preformed in BCEMs to ensure a rapid and high fidelity response to adrenergic stimulation in cardiac muscle. PMID:25561500

  18. Vitexin protects against cardiac hypertrophy via inhibiting calcineurin and CaMKII signaling pathways.

    Science.gov (United States)

    Lu, Cui-cui; Xu, Ying-qi; Wu, Ji-chao; Hang, Peng-zhou; Wang, Yan; Wang, Chen; Wu, Jian-wei; Qi, Jian-cui; Zhang, Yong; Du, Zhi-min

    2013-08-01

    Vitexin is a flavone glycoside isolated from the leaf of Crataeguspinnatifida Bunge, the utility of which has been demonstrated in several cardiovascular diseases. However, its role in cardiac hypertrophy remains unclear. In the present study, we aimed to determine whether vitexin prevents cardiac hypertrophy induced by isoproterenol (ISO) in cultured neonatal rat ventricular myocytes in vitro and pressure overload-induced cardiac hypertrophy in mice in vivo. The results revealed that vitexin (10, 30, and 100 ?M) dose-dependently attenuated cardiac hypertrophy induced by ISO in vitro. Furthermore, vitexin (3, 10, and 30 mg kg(-1)) prevented cardiac hypertrophy induced by transverse aortic constriction as assessed by heart weight/body weight, left ventricular weight/body weight and lung weight/body weight ratios, cardiomyocyte cross-sectional area, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that vitexin inhibited the increment of the resting intracellular free calcium induced by ISO. Vitexin also inhibited the expression of calcium downstream effectors calcineurin-NFATc3 and phosphorylated calmodulin kinase II (CaMKII) both in vitro and in vivo. Taken together, our results indicate that vitexin has the potential to protect against cardiac hypertrophy through Ca2+-mediated calcineurin-NFATc3 and CaMKII signaling pathways. PMID:23624753

  19. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes

    International Nuclear Information System (INIS)

    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca2+ stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca2+ imaging, we found that the depletion of ER/SR Ca2+ stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca2+ ([Ca2+]i), followed by sustained increase depending on extracellular Ca2+. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na+/Ca2+ exchanger inhibitors, inhibited [Ca2+]i relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl3) or by an increased extracellular Ca2+([Ca2+]o) increased the concentration of intracelluar Ca2+, whereas, the sustained elevation of [Ca2+]i was reduced in the presence of SKF96365. Similarly, the duration of [Ca2+]i increase was also shortened in the absence of extracellular Ca2+. Western blot analysis showed that GdCl3 increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl3. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca2+-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.

  20. Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy : the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study

    DEFF Research Database (Denmark)

    Larstorp, Anne Cecilie K; Ariansen, Inger

    2012-01-01

    Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.

  1. PKC? inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Liu, Yanan; Lei, Shaoqing; Gao, Xia; Mao, Xiaowen; Wang, Tingting; Wong, Gordon T; Vanhoutte, Paul M; Irwin, Michael G; Xia, Zhengyuan

    2012-02-01

    Oxidative stress plays critical roles in the development of diabetic cardiovascular complications, including myocardial hypertrophy. The ? isoform of PKC (protein kinase C) is preferentially overexpressed in the myocardium of diabetic subjects accompanied with increased activation of the pro-oxidant enzyme NADPH oxidase, which may exacerbate oxidative stress. We hypothesized that myocardial PKC? is a major upstream mediator of oxidative stress in diabetes and that PKC? inhibition can attenuate myocardial hypertrophy and dysfunction. Control or streptozotocin-induced diabetic rats were treated with the selective PKC? inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the antioxidant NAC (N-acetylcysteine) for 4 weeks. LV (left ventricular) dimensions and functions were detected by echocardiography. 15-F2t-isoprostane (a specific index of oxidative stress) and myocardial activities of superoxide dismutase as well as protein levels of NADPH oxidase were assessed by immunoassay or Western blotting. Echocardiography revealed that the LV mass/body weight ratio was significantly increased in diabetic rats (PRBX normalized these changes with concomitant inhibition of PKC?2 activation and prevention of NADPH oxidase subunit p67phox membrane translocation and p22phox overexpression. The effects of RBX were comparable with that of NAC, except that NAC was inferior to RBX in attenuating cardiac dysfunction. It is concluded that RBX can ameliorate myocardial hypertrophy and dysfunction in diabetes, which may represent a novel therapy in the prevention of diabetic cardiovascular complications. PMID:21892921

  2. Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

    OpenAIRE

    Cabral A.M.; Silva I.F.; Gardioli C.R.; Mauad H.; Vasquez E.C.

    1998-01-01

    Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-...

  3. Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Morisawa, T; Hasegawa, J; Hama, R; Kitano, M; Kishimoto, Y; Kawasaki, H

    1999-01-01

    The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use. PMID:11127807

  4. Efficacy of amiodarone on refractory ventricular fibrillation resistant to lidocaine and cardioversion during weaning from cardiopulmonary bypass in aortic valve replacement for severe aortic stenosis with left ventricular hypertrophy.

    Science.gov (United States)

    Morita, Yoshihisa; Mizuno, Ju; Yoshimura, Tatsuya; Morita, Shigeho

    2010-10-01

    Intravenous injection of amiodarone, a class III anti-arrhythmic is widely used for persistent refractory arrhythmias. We present a case report suggesting the efficacy of amiodarone in refractory ventricular fibrillation (Vf) during weaning from cardiopulmonary bypass (CPB). A 66-year-old woman with hypertension had a medical examination as a result of an episode of palpitations and syncope. Echocardiography and an invasive hemodynamic study revealed severe aortic stenosis (AS) with left ventricular (LV) hypertrophy because of calcified degeneration in a congenital bicuspid aortic valve (AV). Aortic valve replacement (AVR) was scheduled under general anesthesia and CPB. Intraoperative diagnosis was AS with calcified AV, LV hypertrophy, and aneurysm of ascending aorta (Ao). AVR with a biological valve, artificial vessel replacement of ascending Ao, and excision of the outflow myocardial septum were performed under CPB with intermittent antegrade blood cardioplegia at a body temperature (BT) of 24°C. The patient suffered from Vf at a BT of 35.3°C. Vf was not responsive to lidocaine 100 mg and 10 direct current (DC) shocks. After continuous intravenous infusion of amiodarone 225 mg/h for 10 min and a single intravenous injection of amiodarone 150 mg followed by a single DC shock, she returned to normal sinus rhythm. Sinus rhythm was maintained by continuous intravenous infusion of amiodarone 60 mg/h. Total CPB time was 5 h 43 min. Aortic cross-clamping time was 3 h 50 min. Administration of amiodarone is effective for refractory Vf resistant to lidocaine and cardioversion during weaning from CPB in cardiac surgery for heart diseases with LV hypertrophy. PMID:20665054

  5. Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats

    Science.gov (United States)

    Campbell, Stuart G.; Haynes, Premi; Kelsey Snapp, W.; Nava, Kristofer E.

    2013-01-01

    The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P 75 cells for each of the nine age-region groups). The decay time of the Ca2+ transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P 50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion. PMID:23792678

  6. Diagnóstico electrocardiográfico de la Hipertrofia Ventricular Izquierda en pacientes hipertensos. Utilidad del producto duración por voltaje del QRS / Electrocardiography Diagnosis of the Left Ventricular Hypertrophy in hypertensive patients. Usefulness of the product of the duration of voltage of QRS

    Scientific Electronic Library Online (English)

    Juan Lázaro, González Moreno; Belkis, Martínez Martínez; Olga María, Rivero González; Adys H, Salgado Friol; Pablo José, Díaz San Jorge.

    2013-09-01

    Full Text Available Introducción: las enfermedades cardiovasculares provocan la muerte de uno de cada tres cubanos. La Hipertensión arterial (HTA) y consecuentemente la Hipertrofia Ventricular Izquierda (HVI) constituye un factor de riesgo prevalente y capaz de desencadenar serias complicaciones. Objetivo: identificar [...] el comportamiento de los criterios electrocardiográficos de Sokolow, Cornell y el Producto de la Duración por el Voltaje (PDV) del QRS en pacientes con HVI ecocardiográfica. Material y Método: la muestra seleccionada coincide con el universo y consta de 76 pacientes portadores de hipertensión arterial (HTA) atendidos en la consulta de Cardiología. Se les realizó una encuesta sobre la presencia de factores de riesgo, determinación del índice de masa corporal, realización de electrocardiograma y ecocardiograma para establecer la HVI. Resultados: el 61% de los pacientes eran portadores del HVI ecocardiográfica (Prueba de Oro diagnóstica). Para los índices electrocardiográficos de Sokolow y Cornell la sensibilidad (S) fue respectivamente de 22%, y 24%, existiendo en ambos una especificidad (E) de 93%. La (S) para el PDV-Sokolow alcanzó 33%, 22% entre los hombres y 11% entre las mujeres con una (E) total de 97%, mientras el PDV-Cornell tuvo una (S) de 35%, 11% entre los hombres y 24% entre las mujeres, con una (E) total para este índice de 93%. Conclusiones: el ECG es indispensable para el diagnóstico de HVI; el PDV-C y el PDV-S son de mayor sensibilidad diagnóstica que los índices de voltaje aislados; el primero es más útil en mujeres con características epidemiológicas bien definidas. Abstract in english Introduction: cardiovascular diseases cause the death of one out of three Cubans. High Blood Pressure and consequently Left Ventricular Hyperthrophty constitutes a prevalent risk factor able to trigger serious complications. Objective: to identify the behavior of the electrocardiographic approaches [...] of Sokolow, Cornell and the Product of the Duration of Voltage of QRS in patients with Echocardiography Left Ventricular Hypertrophy. Material and Method: the sample coincides with the universe which consists of 76 patients suffering from High Blood Pressure and treated at the Consultation of Cardiology. The patients were surveyed about the presence of risk factors, body mass index and records of electrocardiogram and echocardiogram to confirm their left ventricular hypertrophy. Results: 61% of the patients had echocardiograph left ventricular hypertrophy. For the electrocardiographic indexes of Sokolow and Cornell the sensitivity was 26% and 24% respectively, both tests showed a specificity of 93%. The sensitivity for the Product of the Duration of Voltage for Sokolow reached 33% with a specificity of 97% while the Product of the Duration of Voltage for Cornell had a sensitivity of 35% and a specificity of 93%. Conclusions: ECG is essential in the diagnosis of Left Ventricular Hypertrophy, the Product of the Duration of Voltage for Cornell and the Product of the Duration of Voltage for Sokolow have a higher diagnostic sensitivity than isolated voltage indexes, the former is more useful in women with well defined epidemiological features.

  7. Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause?

    OpenAIRE

    Whyte, Gregory; Sheppard, Mary; George, Keith; Shave, Robert; Prasad, Sanjay; O’Hanlon, Rory; Sharma, Sanjay

    2009-01-01

    We report the case of an experienced, highly trained marathon runner who died suddenly while running. On post-mortem examination, left ventricle hypertrophy and idiopathic interstitial myocardial fibrosis was found. We believe that life-long, repetitive bouts of arduous physical activity resulted in fibrous replacement of the myocardium, causing a pathological substrate for the propagation of fatal arrhythmias.

  8. Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Hakalahti Anna E

    2010-08-01

    Full Text Available Abstract Background The beta-1 adrenergic receptor (?1AR plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly, which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH. Diabetes mellitus (DM, on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI survivors. Methods The study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Results The Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes [62.7 vs. 58.4, respectively (p = 0.023]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001 and LVPWd = 14.2 vs. 12.3 mm (p Conclusions The data suggest an association between the ?1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

  9. La disfunción diastólica en pacientes hipertensos no es debida a hipertrofia ventricular izquierda / Diastolic dysfunction in hypertensive patients is not due to left ventricular hypertrophy / A disfunção diastólica em pacientes hipertensos não é devida à hipertrofia ventricular esquerda

    Scientific Electronic Library Online (English)

    Daniel, Piskorz; Alicia, Tommasi.

    2011-03-01

    Full Text Available Introdução. .A hipertrofia ventricular esquerda (HVE) é uma complicação comum da hipertensão e pode estar associada com disfunção diastólica (DD). Objetivos. Determinar a prevalência de DD em pacientes hipertensos (HT) sem HVE. Material e métodos. Foram incluídos 98 pacientes HT, 66 pacientes sem HV [...] E e 32 pacientes com HVE medida pelo método de Devereux, considerando HVE um índice de massa ventricular esquerda >110 g/m2 em mulheres e 125 g/m2 em homens. Foi realizado Doppler pulsado do orifício da válvula mitral, e foi medida a razão velocidade instantânea pico E / velocidade instantânea pico A (VE/VA) e tempo de relaxamento isovolumétrico (TRIV), ambos foram corrigidos pela idade; e Doppler tecidual do septo interventricular, e foi medida a taxa de pico de velocidade instantânea E'/ pico de velocidade instantânea A' (VE'/VA') e de pico e velocidade instantânea E / pico de velocidade instantânea E' (VE/VE'). Resultados. A média de idade 60,3 ± 36,7 anos, 45 pacientes do sexo masculino (45,9%), 8 pacientes diabéticos (8,2%). A tabela apresenta os resultados da avaliação da função diastólica Conclusões. 1) Alta freqüência de DD em pacientes com hipertensão sem HVE; 2) A única diferença na função diastólica entre pacientes com hipertensão sem e com HVE é maior a pressão diastólica ventricular esquerda expressa por VE/VE'; 3) HVE não é causa do DD em pacientes com hipertensão. Abstract in spanish Introducción. La hipertrofia ventricular izquierda (HVI) es una complicación frecuente en hipertensión arterial y se puede acompañar de disfunción diastólica (DD). Objetivos. Determinar la prevalencia de DD en pacientes hipertensos (HT) sin HVI. Material y métodos. Se incluyeron 98 pacientes con HT, [...] 66 pacientes sin HVI y 32 pacientes con HVI medida por método de Devereux, considerándose HVI un índice de masa ventricular izquierda >110 g/m2 en mujeres y 125 g/m2 en hombres. Se efectuó Doppler pulsado del orificio valvular mitral y se midió la relación velocidad instantánea pico E/velocidad instantánea pico A (VE/VA) y el tiempo de relajación isovolumétrica (TRIV), ambos fueron corregidos por edad, y Doppler tisular del septum interventricular, midiéndose la relación velocidad instantánea pico E´/velocidad instantánea pico A´ (VE´/VA´) y velocidad instantánea pico E/velocidad instantánea pico E´ (VE/VE´). Resultados. Edad media: 60,3±36,7 años; sexo masculino: 45 pacientes (45,9 %); 8 pacientes diabéticos (8,2%). La tabla presenta los resultados de la evaluación de función diastólica. Conclusiones. 1) Alta frecuencia de DD en pacientes HT sin HVI. 2) La única diferencia en la función diastólica entre pacientes HT sin y con HVI es la mayor presión de fin de diástole del ventrículo izquierdo expresada por VE/VE´. 3) La HVI no es la causa de DD en pacientes HT. Abstract in english Background. Left ventricular hypertrophy (LVH) is a common complication of hypertension and may be associated with diastolic dysfunction (DD). Objectives. To determine the prevalence of DD in hypertensive (HT) patients without LVH. Methods and material. 98 HT patients were included, 66 with LVH and [...] 32 without LVH measured by the method ofDevereux, LVH was considered a left ventricular mass index >110 g/m2 in women and 125 g/m2 in men. Mitral valve orifice pulsed Doppler was performed and it was measured the peak instantaneous velocity ratio E/A (VE/VA) and isovolumetric relaxation time (IVRT), both were corrected by age; and tissue Doppler of the interventricular septum was also preformed, and it was measured the peak instantaneous velocity ratio E'/A' (VE'/ VA') and instantaneous velocity peak E/E' (VE/VE'). Results. Mean age 60.3±36.7 years, male 45 patients (45,9%), 8 diabetic patients (8.2%). The table presents the results of the assessment of diastolic function. Conclusions. 1) High frequency of DD in HT patients without LVH, 2) The only one difference between patients with and without LVH was the higher end diastolic left vent

  10. Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation

    Directory of Open Access Journals (Sweden)

    Bassani R.A.

    2003-01-01

    Full Text Available Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A, Na+-Ca2+ exchanger (NCX and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake. To estimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW. Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 µM, whereas SR-dependent flux was lower with TG-TW (77 vs 81 µM. The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.

  11. Differential effects of the sodium calcium exchange inhibitor, KB-R7943, on ischemia and reperfusion injury in isolated guinea pig ventricular myocytes.

    Science.gov (United States)

    MacDonald, Ashley C; Howlett, Susan E

    2008-02-01

    Effects of the Na(+)-Ca(2+) exchange (NCX) inhibitor KB-R7943 on electrical and contractile function were examined in guinea pig ventricular myocytes exposed to ischemia and reperfusion. Action potentials and transmembrane currents were recorded with microelectrodes; contractions were measured with an edge detector. Cells were exposed to simulated ischemia (hypoxia, hypercapnia, hyperkalemia, acidosis, lactate accumulation, no glucose) for 20 min and reperfused with Tyrode's solution. Experiments were conducted at 37 degrees C in the absence or presence of KB-R7943. Low concentrations of KB-R7943 (0.1 microM) had little impact on changes in contractions, membrane potential, or Ca(2+) current induced by ischemia and reperfusion. However, higher concentrations of KB-R7943 (0.5 and 1.0 microM) reduced the magnitude of Ca(2+) current and promoted action potential abbreviation in both ischemia and reperfusion. High concentrations of KB-R7943 also promoted post-ischemic contractile dysfunction (stunning) in reperfusion. In the absence of KB-R7943, the arrhythmogenic transient inward current (I(TI)) plus aftercontractions occurred upon reperfusion, and some cells exhibited irreversible cell injury (hypercontracture). Higher concentrations of KB-R7943 (0.5 and 1.0 micoM) did not affect the occurrence or magnitude of I(TI) and aftercontractions and did not affect the occurrence of hypercontracture. In contrast, 0.1 microM KB-R7943 virtually abolished I(TI), aftercontractions and hypercontracture. Thus, low concentrations of KB-R7943 protected against ischemia and reperfusion injury, but higher concentrations of drug actually exacerbated detrimental effects of ischemia and reperfusion. These results suggest that inhibition of I(TI) may contribute to the antiarrhythmic effects of KB-R7943 on reperfusion-induced arrhythmias. PMID:18036586

  12. Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation

    Scientific Electronic Library Online (English)

    R.A., Bassani; J.W.M., Bassani.

    1717-17-01

    Full Text Available Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A), Na+-Ca2+ exchanger (NCX) and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake). To e [...] stimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT) and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW). Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 µM), whereas SR-dependent flux was lower with TG-TW (77 vs 81 µM). The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively) and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively) in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.

  13. The H{sub 1}–H{sub 2} domain of the ?{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li, E-mail: wangyongli@gmail.com

    2012-07-01

    The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of ?{sub 1} and ?{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the ?{sub 1} or ?{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 ?M) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 ?M but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA ?{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ? We prepared two antibodies against the H{sub 1}-H{sub 2} domain of ?{sub 1} and ?{sub 2} isoforms of NKA. ? The H{sub 1}-H{sub 2} domain of the NKA ?{sub 1} isoform mediates OUA-induced cardiac toxicity. ? The H{sub 1}-H{sub 2} domain of the NKA ?{sub 2} isoform mediates OUA-induced positive inotropic.

  14. Cardiac MRI in a Patient with Coincident Left Ventricular Non-Compaction and Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Zahra Alizadeh-Sani

    2011-12-01

    Full Text Available Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy that affects both children and adults. Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular non-compaction and establish prognostic factors. We report a 47-year-old woman with a history of dilated cardiomyopathy with unknown etiology. Echocardiography showed mild left ventricular enlargement with severe systolic dysfunction (EF = 20-25%. According to cardiac magnetic resonance imaging findings non-compaction left ventricle with hypertrophic cardiomyopathy was considered, and right ventricular septal biopsy was recommended. Right ventricular endomyocardial biopsy showed moderate hypertrophy of cardiac myocytes with foci of myocytolysis and moderate interstitial fibrosis. No evidence of infiltrative deposition was seen.

  15. Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography

    Scientific Electronic Library Online (English)

    Paulo, Ginefra; Eduardo C., Barbosa; P. R., Benchimol-Barbosa; Alfredo S., Bomfim; Sílvia H., Boghossian; Angelo A., Salgado; Flávia G., Brasil; Elizabete A., Freitas; Francisco M., Albanesi Filho.

    2003-07-01

    Full Text Available OBJECTIVE: To assess signal-averaged electrocardiogram (SAECG) for diagnosing incipient left ventricular hypertrophy (LVH). METHODS: A study with 115 individuals was carried out. The individuals were divided as follows: GI - 38 healthy individuals; GII - 47 individuals with mild to moderate hyperten [...] sion and normal findings on echocardiogram and ECG; and GIII - 30 individuals with hypertension and documented LVH. The magnitude vector of the SAECG was analyzed with the high-pass cutoff frequency of 40 Hz through the bidirectional four-pole Butterworth high-pass digital filter. The mean quadratic root of the total QRS voltage (RMST) and the two-dimensional integral of the QRS area of the spectro-temporal map were analyzed between 0 and 30 Hz for the frequency domain (Int FD), and between 40 and 250 Hz for the time domain (Int TD). The electrocardiographic criterion for LVH was based on the Cornell Product. Left ventricular mass was calculated with the Devereux formula. RESULTS: All parameters analyzed increased from GI to GIII, except for Int FD (GII vs GIII) and RMST log (GII vs GIII). Int TD showed greater accuracy for detecting LVH with an appropriate cutoff > 8 (sensitivity of 55%, specificity of 81%). Positive values (> 8) were found in 56.5% of the G II patients and in 18.4% of the GI patients (p

  16. Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography

    Directory of Open Access Journals (Sweden)

    Ginefra Paulo

    2003-01-01

    Full Text Available OBJECTIVE: To assess signal-averaged electrocardiogram (SAECG for diagnosing incipient left ventricular hypertrophy (LVH. METHODS: A study with 115 individuals was carried out. The individuals were divided as follows: GI - 38 healthy individuals; GII - 47 individuals with mild to moderate hypertension and normal findings on echocardiogram and ECG; and GIII - 30 individuals with hypertension and documented LVH. The magnitude vector of the SAECG was analyzed with the high-pass cutoff frequency of 40 Hz through the bidirectional four-pole Butterworth high-pass digital filter. The mean quadratic root of the total QRS voltage (RMST and the two-dimensional integral of the QRS area of the spectro-temporal map were analyzed between 0 and 30 Hz for the frequency domain (Int FD, and between 40 and 250 Hz for the time domain (Int TD. The electrocardiographic criterion for LVH was based on the Cornell Product. Left ventricular mass was calculated with the Devereux formula. RESULTS: All parameters analyzed increased from GI to GIII, except for Int FD (GII vs GIII and RMST log (GII vs GIII. Int TD showed greater accuracy for detecting LVH with an appropriate cutoff > 8 (sensitivity of 55%, specificity of 81%. Positive values (> 8 were found in 56.5% of the G II patients and in 18.4% of the GI patients (p< 0.0005. CONCLUSION: SAECG can be used in the early diagnosis of LVH in hypertensive patients with normal ECG and echocardiogram.

  17. Left ventricular function and cardiac hypertrophy in the cases of mild hypertension with marked ST-T changes in electrocardiogram

    International Nuclear Information System (INIS)

    The characteristics of the hemodynamic pattern and cardiac hypertrophy of mild hypertensive patients with giant negative T waves in electrocardiogram (ECG) (group I, 12 patients) were examined by the radionuclide methods, the cardiac catheterization and the echocardiogram. As control groups, the patients of essential hypertension (EH) with high voltage in ECG (group II, 36 patients), those with high voltage and mild ST-T changes in ECG (group III, 9 patients), and the patients with normotensive hypertrophic cardiomyopathy (group IV, 8 patients) were studied. Ejection fraction and cardiac index in group I were increased compared with those in group II (p 201Tl) myocardial images was significantly lower than in group II and III (p 201Tl-uptake index in cardiac apex determined by apical/total counts was increased in group I compared with other groups. These results suggest that group I is hyperkinetic state and has marked apical hypertrophy. The possibility exists that the increased afterload might be a trigger of apical hypertropoad might be a trigger of apical hypertrophy in predisposed individuals. (author)

  18. Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats.

    Science.gov (United States)

    Carneiro-Júnior, M A; Pelúzio, M C G; Silva, C H O; Amorim, P R S; Silva, K A; Souza, M O; Castro, C A; Roman-Campos, D; Prímola-Gomes, T N; Natali, A J

    2010-11-01

    We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), treadmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C) were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 ?m, P TRA than in SED-8 (8.50 ± 0.08 vs 8.22 ± 0.10, P TRA cells exhibited higher maximum velocity of shortening than SED-8 (102.01 ± 4.50 vs 82.01 ± 5.30 ?m/s, P TRA cells than in SED-8 (88.20 ± 4.01 vs70.01 ± 4.80 ?m/s, P left ventricle remodeling in SHR towards eccentric hypertrophy, which remained after detraining. It also improved single left ventricular myocyte contractile function, which was reversed by detraining. PMID:21049244

  19. Effect of Ca2+ Efflux Pathway Distribution and Exogenous Ca2+ Buffers on Intracellular Ca2+ Dynamics in the Rat Ventricular Myocyte: A Simulation Study.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Orchard, C.

    2014-01-01

    Ro?. 2014, ?. 2014 (2014), s. 920208. ISSN 2314-6133 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : calcium efflux * calcium buffers * cardiac myocyte * computer model Subject RIV: BO - Biophysics

  20. Electrophysiological effect and the gating mechanism of astragaloside IV on l-type Ca(2+) channels of guinea-pig ventricular myocytes.

    Science.gov (United States)

    Zhao, Meimi; Shao, Dongxue; Yu, Lifeng; Sun, Xuefei; Wang, Yan; Hu, Huiyuan; Feng, Rui; Gao, Qinghua; Guo, Feng; Hao, Liying

    2015-08-01

    Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV?s effects on Ca(2+) channel activity of single cardiomyocytes and single Ca(2+) channels. Whole-cell Ca(2+) currents in freshly dissociated cardiomyocytes were measured using the whole-cell patch-clamp technique. Single Ca(2+) channel currents were examined in cell-attached patches and inside-out patches. In the whole-cell recording, AS-IV reduced the amplitude of l-type Ca(2+) currents (ICaL) in a concentration-dependent manner. Although AS-IV did not alter the steady-state activation curves, the voltage dependence of the current inactivation curves was negatively shifted by AS-IV in a concentration dependent manner. Consistent with the results of the whole-cell recording, in the inside-out configuration the ensemble average of single Ba(2+) current via l-type Ca(2+) channel was dose-dependently reduced by AS-IV. The reduction of unitary Ba(2+) current at 0.1 or 1µM AS-IV was accounted for a decrease in the channel activity (NPo). In addition to the decrease in NPo, there was a reduction of Po without a change in channel number or an apparent change in single channel current. Furthermore, we found that the open-closed kinetics of the channel were affected by AS-IV. AS-IV induced the shift of l-type Ca(2+) channels from either brief openings (mode 1) or long-lasting openings (mode 2) to no active opening (mode 0). Our results suggest that AS-IV blocks the currents through Ca(2+) channels in guinea-pig ventricular myocytes by affecting the open-closed kinetics of l-type Ca(2+) channels to inhibit the channel activities. This study could provide theoretical basis for the drug exploiting of the monomer of Astragalus membranaceus. PMID:25891370

  1. Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases.

    Science.gov (United States)

    Leroy, Jérôme; Abi-Gerges, Aniella; Nikolaev, Viacheslav O; Richter, Wito; Lechêne, Patrick; Mazet, Jean-Luc; Conti, Marco; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2008-05-01

    Steady-state activation of cardiac beta-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. To evaluate the time course of the cAMP changes in the different compartments, brief (15 seconds) pulses of isoprenaline (100 nmol/L) were applied to adult rat ventricular myocytes (ARVMs) while monitoring cAMP changes beneath the membrane using engineered cyclic nucleotide-gated channels and within the cytosol with the fluorescence resonance energy transfer-based sensor, Epac2-camps. cAMP kinetics in the two compartments were compared to the time course of the L-type Ca(2+) channel current (I(Ca,L)) amplitude. The onset and recovery of cAMP transients were, respectively, 30% and 50% faster at the plasma membrane than in the cytosol, in agreement with a rapid production and degradation of the second messenger at the plasma membrane and a restricted diffusion of cAMP to the cytosol. I(Ca,L) amplitude increased twice slower than cAMP at the membrane, and the current remained elevated for approximately 5 minutes after cAMP had already returned to basal level, indicating that cAMP changes are not rate-limiting in channel phosphorylation/dephosphorylation. Inhibition of PDE4 (with 10 micromol/L Ro 20-1724) increased the amplitude and dramatically slowed down the onset and recovery of cAMP signals, whereas PDE3 blockade (with 1 micromol/L cilostamide) had a minor effect only on subsarcolemmal cAMP. However, when both PDE3 and PDE4 were inhibited, or when all PDEs were blocked using 3-isobutyl-l-methylxanthine (300 micromol/L), cAMP signals and I(Ca,L) declined with a time constant >10 minutes. cAMP-dependent protein kinase inhibition with protein kinase inhibitor produced a similar effect as a partial inhibition of PDE4 on the cytosolic cAMP transient. Consistently, cAMP-PDE assay on ARVMs briefly (15 seconds) exposed to isoprenaline showed a pronounced (up to approximately 50%) dose-dependent increase in total PDE activity, which was mainly attributable to activation of PDE4. These results reveal temporally distinct beta-adrenergic receptor cAMP compartments in ARVMs and shed new light on the intricate roles of PDE3 and PDE4. PMID:18369156

  2. Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice / Própolis e natação na prevenção da aterogênese e hipertrofia ventricular esquerda de camundongos hipercolesterolêmicos

    Scientific Electronic Library Online (English)

    DB., Silva; AP., Miranda; DB., Silva; LRB., D`Angelo; BB., Rosa; EA., Soares; JGDC., Ramalho; MFG., Boriollo; JAD., Garcia.

    2015-05-01

    Full Text Available Objetivos O presente estudo verificou o efeito do própolis associação ou não com a natação na dislipidemia, na hipertrofia ventricular esquerda e aterogênese de camundongos hipercolesterolêmicos. Métodos e Resultados Os experimentos foram realizados em camundongos LDLr–/–, alimentados com dieta hip [...] erlipídica por 75 dias, e divididos em quatro grupos experimentais (n = 10): HL, sedentários, foram submetidos ao estresse aquático (5 min por dia, cinco vezes por semana); NAT foram submetidos a um protocolo de natação (1 hora por dia, cinco vezes por semana) a partir do 16° dia do experimento; PRO, sedentários, submetidos a estresse aquático e que receberam extrato de própolis oral (70 uL / animal / dia) a partir do 16° dia do experimento; HL + NAC + PRO, submetidos a natação e que recebeu a própolis, como descrito acima. Após 75 dias, foi coletado sangue para análise do perfil lipídico. Calculou-se a relação entre o peso ventricular (mg) e o peso do animal (g). Os cortes histológicos do coração e aorta foram processados imunohistoquímicamente com anticorpos anti-CD40L para avaliar o processo inflamatório, corados com hematoxilina / eosina e picrossírius red, para avaliar as alterações morfológicas e morfométricas. Os camundongos HL apresentaram dislipidemia grave, aterogênese e hipertrofia do ventrículo esquerdo, associada a uma diminuição dos níveis plasmáticos de HDLc e o desenvolvimento subsequente do processo inflamatório cardiovasculares, caracterizada pelo aumento da expressão do CD40L no ventrículo esquerdo e na aorta. Natação e a própolis isolado e \\ ou associados preveniram a HVE, a aterogênese e a inflamação tanto na artéria quanto no ventrículo, diminuindo a expressão de CD40L, aumentando os níveis plasmáticos de HDLc. Conclusão A Própolis isolada ou associada a uma atividade física regular é benéfica na proteção cardiovascular através da ação anti-inflamatória. Abstract in english Aims The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. Methods and Results The experiments were performed in LDLr–/– mice, fed with high fat diet for 75 days, and we [...] re divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and\\or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. Conclusion Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action.

  3. Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.

    OpenAIRE

    Myerson, SG; Montgomery, HE; Whittingham, M; Jubb, M; World, MJ; Humphries, SE; Pennell, DJ

    2001-01-01

    BACKGROUND: Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp marker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular growth factor angiotensin II on the angiotensin type 1 (AT(1)) receptor or increased degradation of growth-inhibiting kinins....

  4. Índice tornozelo-braquial e hipertrofia ventricular na hipertensão arterial Índice tobillo-braquial y hipertrofia ventricular en la hipertensión arterial Ankle-brachial index and ventricular hypertrophy in arterial hypertension

    Directory of Open Access Journals (Sweden)

    Pedro Ferreira de Albuquerque

    2012-01-01

    Full Text Available O ?ndice Tornozelo-Braquial (ITB é marcador de doença arterial obstrutiva periférica. Raros relatos correlacionam esse índice com hipertrofia ventricular esquerda (HVE, capacidade funcional (CF e escore de risco coronariano de Framingham (ERCF. O objetivo do trabalho foi verificar a correlação entre ITB, HVE, CF e ERCF em homens com hipertensão arterial (HA. Estudo prospectivo e transversal de pacientes do sexo masculino (n = 40, com idade média de 57,92 ± 7,61 anos, sem complicações cardiovasculares. Essa população foi submetida às medidas de ITB, ecocardiograma (ECO, teste ergométrico (TE e exames laboratoriais. O ITB (direito e esquerdo foi considerado anormal quando a relação entre a maior média das pressões sistólicas dos tornozelos e dos braços foi inferior ou igual a 0,9 ou superior a 1,3 mmHg. A HVE foi identificada pelo ECO transtorácico; e a CF, pelo TE. Amostras sanguíneas periféricas foram colhidas para o cálculo do ERCF. Valores normais de ITB foram encontrados em 33 pacientes (82,5%, os quais foram incluídos no Grupo I; sete pacientes (17,5% com ITB anormal constituíram o Grupo II. Os índices de massa do índice de massa do ventrículo esquerdo (IMVE ao ECO foram de 111,18 ± 34,34 g/m² (Grupo I e de 150,29 ± 34,06 g/m2 (Grupo II (p = 0,009. A prevalência de HVE foi de 4% (Grupo I e de 35,3% (Grupo II (p = 0,01, constatando-se diferenças significativas entre os grupos. Quanto à CF no TE, não se registrou diferença entre os grupos. Em relação ao ERCF, a média do Grupo I foi inferior à média do Grupo II: 13,18 ± 2,11 versus 15,28±1,79 (p = 0,019. Em HA, a presença de HVE definida pelo IMVE esteve mais presente nos casos com ITB anormal, identificando maior risco cardiovascular.El Índice Tobillo-Braquial (ITB es un marcador de enfermedad arterial obstructiva periférica. Raros relatos correlacionan ese índice con la hipertrofia ventricular izquierda (HVI, capacidad funcional (CF y puntación de riesgo coronario de Framingham (PRCF. El objetivo de este estudio fue verificar la correlación entre ITB, HVI, CF y PRCF en hombres con hipertensión arterial (HA. Estudio prospectivo y transversal de pacientes del sexo masculino (n = 40, con edad promedio de 57,92 ± 7,61 años, sin complicaciones cardiovasculares. Esa población fue sometida a las medidas de ITB, ecocardiograma (ECO, test ergométrico (TE y exámenes de laboratorio. El ITB (derecho e izquierdo, se consideró anormal cuando la relación entre la mayor media de las presiones sistólicas de los tobillos y de los brazos fue inferior o igual a 0,9 o superior a 1,3 mmHg. La HVI fue identificada por el ECO transtorácico; y la CF por el TE. Muestras sanguíneas periféricas se recogieron para el cálculo del PRCF. Valores normales de ITB fueron encontrados en 33 pacientes (82,5%, los cuales se incluyeron en el Grupo I; siete pacientes (17,5% con ITB anormal formaron el Grupo II. Los índices de masa del índice de masa del ventrículo izquierdo (IMVI al ECO fueron de 111,18 ± 34,34 g/m² (Grupo I y de 150,29 ± 34,06 g/m² (Grupo II (p = 0,009. La prevalencia de HVI fue de 4% (Grupo I y de 35,3% (Grupo II (p = 0,01, siendo comprobadas las diferencias significativas entre los grupos. En cuanto a la CF en el TE, no se registró ninguna diferencia entre los grupos. Con relación al PRCF, el promedio del Grupo I quedó por debajo del promedio del Grupo II: 13,18 ± 2,11 versus 15,28±1,79 (p = 0,019. En HA, la presencia de HVI definida por el IMVI estuvo más presente en los casos con ITB anormal, identificando un mayor riesgo cardiovascular.The ankle-brachial index (ABI is a marker of peripheral arterial disease. Very few reports have correlated this index with left ventricular hypertrophy (LVH, functional capacity (FC and Framingham risk score (FRS. The objective of this study was to verify the correlation between ABI, LVH, FC and FRS in men with arterial hypertension (AH. Prospective and cross-sectional study of male patients (n = 40 with a mean age of 57.92 ± 7.61 years and no cardiovascula

  5. Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy.

    Science.gov (United States)

    Fossum, E; Olsen, M H; Høieggen, A; Wachtell, K; Reims, H M; Ibsen, H; Julius, S; Kjeldsen, S E

    2004-06-01

    Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study. PMID:15057253

  6. Effect of fosinopril on progression of the asymptomatic carotid atherosclerosis and left ventricular hypertrophy in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Tasi? Ivan

    2006-01-01

    Full Text Available INTRODUCTION The cardiovascular changes (vascular structure changes, hypertrophy of the left ventricle contribute to both the increased cardiovascular morbidity and the mortality of essential hypertension. Therefore, modern treatment strategies should not only target blood pressure (BP reduction but also normalize cardiovascular structure and function. OBJECTIVE Aim of the study was to determine the effect of the ACE inhibitor Fosinopril on the Intima-media thickness of the common carotid artery and on the left ventricle mass after 9-month treatment of hypertensive patients. METHOD The study included 40 patients with the arterial hypertension and the left ventricle hypertrophy verified by echocardiography. The patients were randomized on A ACE-inhibitor - Fosinopril and 6 without ACE inhibitor - atenolol, and they were followed up 9 months. The groups were not different by age, sex, and metabolic status. Color Duplex ultrasonography of the carotid arteries was performed by Acuson Sequia C236 with high-frequency linear probe of 8 MHz. The Intima-media thickness of the common carotids on the left and the right was measured in diastole at 1.5. cm from the highest point of bifurcation under maximal magnification. Using the same device, the left ventricle mass and other parameters of the left ventricle were determined in M-mode and by means of 2D image. RESULTS After 9 months, BP In both groups Was reduced In similar range (group A: systolic BP from 158 to 137 mmHg, and diastolic BP from 94 to 85 mmHg, and group B; systolic BP from 164 to 137 mmHg, and diastolic BP from 87 to 84 mmHg. The thickness of the intimomedial complex in patients using Fosinopril was decreased by 0.0278 ± 0.03 mm, while in the group of patients that did not use the ACE-inhibitor, it was increased by 0.078 ±0.13 mm. The left ventricle mass in patients using Fosinopril was decreased by 5 grams (312 ± 72 g vs. 307 ± 77 g, while in group B patients, it was increased by 15 grams (323 ± 79 g vs. 328 ± 58 g. Diastolic function expressed through relation E/A was improved minimally in the group A, while it worsened by 0.1 in the group B. After 9 months, serious cardiovascular events were recorded (one infarction of myocardium and one hospitalization due to the unstable angina pectoris in two patients of the group A, while four patients of the group B. had serious CV events (1 cerebrovascular stroke and 3 hospitalizations due to unstable angina pectoris. CONCLUSION The results of our study showed that the application of Fosinopril in patients with the arterial hypertension and the left ventricle hypertrophy could efficiently block further progression of the intima-medial thickness of the common carotid artery, reduce the left ventricle mass, and improve. diastolic function of the left ventricle.

  7. Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca / Myocardial function during the transition from compensated left ventricular hypertrophy to failure

    Scientific Electronic Library Online (English)

    Antonio Carlos, Cicogna; Kathleen G., Robinson; Chester H., Conrad; Robin, Squire; Marina P., Okoshi; Oscar H. L., Bing.

    1997-12-01

    Full Text Available OBJETIVO: Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR). MÉTODOS: Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíac [...] a (SHR-IC) e sem falência cardíaca (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contrações isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ºC). RESULTADOS: Os valores da tensão máxima desenvolvida (TD) e da velocidade máxima de encurtamento (Vmáx) foram menores nos SHR-IC e SHR, em relação aos WKY (p0,05). A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p0,05). CONCLUSÃO: Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associada ao aumento da rigidez passiva do miocárdio e não à piora da função contrátil do músculo cardíaco. Abstract in english PURPOSE: To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR). METHODS: Isolated left ventricular papillary muscle function was studied [...] in SHR with heart failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF), and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28ºC. RESULTS: Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p0.05). CONCLUSION: These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function.

  8. Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca Myocardial function during the transition from compensated left ventricular hypertrophy to failure

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Cicogna

    1997-12-01

    Full Text Available OBJETIVO: Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR. MÉTODOS: Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC e sem falência cardíaca (SHR e de ratos normotensos controle Wistar-Kyoto (WKY foram estudados em contrações isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ºC. RESULTADOS: Os valores da tensão máxima desenvolvida (TD e da velocidade máxima de encurtamento (Vmáx foram menores nos SHR-IC e SHR, em relação aos WKY (p0,05. A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p0,05. CONCLUSÃO: Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associada ao aumento da rigidez passiva do miocárdio e não à piora da função contrátil do músculo cardíaco.PURPOSE: To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR. METHODS: Isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F, in age-matched SHR without evidence of heart failure (SHR-NF, and in nonhypertensive controls Wistar-Kyoto rats (WKY. Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28ºC. RESULTS: Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p0.05. CONCLUSION: These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function.

  9. Coronary artery disease, left ventricular hypertrophy and diastolic dysfunction are associated with stroke in patients affected by persistent non-valvular atrial fibrillation: a case-control study

    Directory of Open Access Journals (Sweden)

    Andrea Passantino

    2009-04-01

    Full Text Available Persistent non-valvular atrial fibrillation (NVAF is associated with an increased risk of cardiovascular events such as stroke, and its rate is expected to rise because of the ageing population. The absolute rate of stroke depends on age and comorbidity. Risk stratification for stroke in patients with NVAF derives from populations enrolled in randomized clinical trials. However, participants in clinical trials are often not representative of the general population. Many stroke risk stratification scores have been used, but they do not include transthoracic echocardiogram (TTE, pulsate wave Doppler (PWD and tissue Doppler imaging (TDI, simple and non-invasive diagnostic tools. The role of TTE, PWD and TDI findings has not been previously determined. Our study goal was to determine the association between TTE and PWD findings and stroke prevalence in a population of NVAF prone outpatients. Patients were divided into two groups: P for stroke prone and F for stroke free. There were no statistically significant differences between the two groups concerning cardiovascular risk factors, age (p=0.2, sex (p=0.2, smoking (p=0.3, diabetes (p=0.1 and hypercholesterolemia (p=0.2; hypertension was statistically significant (p less than 0.001. There were statistically significant differences concerning coronary artery disease, previous acute myocardial infarction (AMI (p less than 0.05 and non- AMI coronaropathy (p less than 0.04, a higher rate being in the P group. Concerning echo-Doppler findings, a higher statistically significant rate of left ventricular hypertrophy (LVH (p less than  0.05 and left ventricular diastolic dysfunction (p less than 0.001 was found in the P group and dilated left atrium (p less than  0.04 in the F group, the difference was not significant for mitral regurgitation (p=0.7. Stroke prone NVAF patients have a higher rate of hypertension, coronary artery disease, with and without AMI, LVH and left ventricular diastolic dysfunction, but not left atrial dilatation. M-B mode echocardiography and PWD examination help to identify high-risk stroke patients among NVAF subjects; therefore, they may help in the selection of appropriate therapy for each patient.

  10. Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Orchard, C.

    2012-01-01

    Ro?. 41, ?. 6 (2012), s. 491-503. ISSN 0175-7571 Institutional research plan: CEZ:AV0Z20760514 Keywords : t-tubules * rat * cardiac myocyte * computer model * calcium Subject RIV: BO - Biophysics Impact factor: 2.274, year: 2012

  11. Selective Knockout of Mouse ERG1 B Potassium Channel Eliminates IKr in Adult Ventricular Myocytes and Elicits Episodes of Abrupt Sinus Bradycardia

    Science.gov (United States)

    Lees-Miller, James P.; Guo, Jiqing; Somers, Julie R.; Roach, Dan E.; Sheldon, Robert S.; Rancourt, Derrick E.; Duff, Henry J.

    2003-01-01

    The ERG1 gene encodes a family of potassium channels. Mutations in human ERG1 lead to defects in cardiac repolarization, referred to as the long QT syndrome. Through homologous recombination in mouse embryonic stem cells the ERG1 B potassium channel transcript was eliminated while the ERG1 A transcript was maintained. Heterologous expression of ERG1 isoforms had previously indicated that the deactivation time course of ERG1 B is 10-fold more rapid than that of ERG1 A. In day-18 fetal +/+ myocytes, IKr exhibited two time constants of deactivation (3,933 ± 404 and 350 ± 19 ms at ?50 mV), whereas in age-matched ERG1 B?/? mice the rapid component was absent. Biexponential deactivation rates (2,039 ± 268 and 163 ± 43 ms at ?50 mV) were also observed in adult +/+ myocytes. In adult ERG1 B?/? myocytes no IKr was detected. Electrocardiogram intervals were similar in +/+ and ?/? mice. However, adult ?/? mice manifested abrupt spontaneous episodes of sinus bradycardia (>100 ms of slowing) in 6 out of 21 mice. This phenomenon was never observed in +/+ mice (0 out of 16). We conclude that ERG1 B is necessary for IKr expression in the surface membrane of adult myocytes. Knockout of ERG1 B predisposes mice to episodic sinus bradycardia. PMID:12612061

  12. Selective knockout of mouse ERG1 B potassium channel eliminates I(Kr) in adult ventricular myocytes and elicits episodes of abrupt sinus bradycardia.

    Science.gov (United States)

    Lees-Miller, James P; Guo, Jiqing; Somers, Julie R; Roach, Dan E; Sheldon, Robert S; Rancourt, Derrick E; Duff, Henry J

    2003-03-01

    The ERG1 gene encodes a family of potassium channels. Mutations in human ERG1 lead to defects in cardiac repolarization, referred to as the long QT syndrome. Through homologous recombination in mouse embryonic stem cells the ERG1 B potassium channel transcript was eliminated while the ERG1 A transcript was maintained. Heterologous expression of ERG1 isoforms had previously indicated that the deactivation time course of ERG1 B is 10-fold more rapid than that of ERG1 A. In day-18 fetal +/+ myocytes, I(Kr) exhibited two time constants of deactivation (3,933 +/- 404 and 350 +/- 19 ms at -50 mV), whereas in age-matched ERG1 B(-/-) mice the rapid component was absent. Biexponential deactivation rates (2,039 +/- 268 and 163 +/- 43 ms at -50 mV) were also observed in adult +/+ myocytes. In adult ERG1 B(-/-) myocytes no I(Kr) was detected. Electrocardiogram intervals were similar in +/+ and -/- mice. However, adult -/- mice manifested abrupt spontaneous episodes of sinus bradycardia (>100 ms of slowing) in 6 out of 21 mice. This phenomenon was never observed in +/+ mice (0 out of 16). We conclude that ERG1 B is necessary for I(Kr) expression in the surface membrane of adult myocytes. Knockout of ERG1 B predisposes mice to episodic sinus bradycardia. PMID:12612061

  13. Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients

    Directory of Open Access Journals (Sweden)

    Felício João S

    2006-09-01

    Full Text Available Abstract Background The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes. Methods Ninety-one hypertensive patients with type 2 diabetes mellitus (DM (group-1 [G1], 59 essential hypertensive patients (group-2 [G2] and 26 healthy controls (group-3 [G3] were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM and echocardiography (ECHO with Doppler. We calculated an average of fasting blood glucose (AFBG values of G1 from the previous 4.2 years and a glycemic control index (GCI (percentual of FBG above 200 mg/dl. Results G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP and LVMI (NSBP = 132 ± 18 vs 124 ± 14 mmHg; P 2; P 165 mg/dl showed an additional risk of LVH (P Conclusion This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.

  14. Management of high-risk patients with hypertension and left ventricular hypertrophy in Germany: differences between cardiac specialists in the inpatient and outpatient setting

    Directory of Open Access Journals (Sweden)

    Wegscheider Karl

    2006-10-01

    Full Text Available Abstract Background Among patients with hypertension, those with established left ventricular hypertrophy (LVH represent a high risk cohort with poor prognosis. We aimed to investigate differences in characteristics and health care management of such patients treated as inpatients or outpatients by cardiac specialists. Methods Prospective cross-sectional study in patients with hypertension and LVH who were referred to either inpatient care (rehabilitation hospitals or to outpatient care (cardiology practices. Results A total of 6358 inpatients (59.6% males; mean age 66.6 years and 2246 outpatients (59.5% males; mean age 63.2 years were followed up for a mean of 23 vs. 52 days, respectively. Inpatients compared to outpatients had a significantly higher prevalence of coronary heart disease, history of stroke, renal failure or diabetes. Mean blood pressure of inpatients compared to outpatients was significantly lower both at entry (150/84 vs. 161/93 mmHg and at end of follow-up (129/75 vs. 139/83 mmHg. After adjustment for baseline blood pressure and a propensity score, differences between out- and inpatients at end of follow-up were 8.0/5.1 mmHg in favour of inpatients. Blood pressure goals as specified by guidelines were not met by 32% of inpatients and 55% of outpatients. Conclusion Inpatients had a higher rate of comorbidities and more advanced atherosclerotic disease than outpatients. Control of hypertension of inpatients was already better on admission than in outpatients, and treatment intensity in this group was also higher during the observation period. While blood pressure lowering was substantial in both groups, there were still a high proportion of patients who did not achieve treatment goals at discharge.

  15. Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).

    Science.gov (United States)

    Verdecchia, Paolo; Reboldi, Gianpaolo; Di Pasquale, Giuseppe; Mazzotta, Giovanni; Ambrosio, Giuseppe; Yang, Sean; Pogue, Janice; Wallentin, Lars; Ezekowitz, Michael D; Connolly, Stuart J; Yusuf, Salim

    2014-02-15

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF. PMID:24359765

  16. False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had ''significant'' (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH. (orig.)

  17. Anthracycline treatment and ventricular remodeling in left ventricular assist device patients.

    Science.gov (United States)

    Segura, Ana Maria; Radovancevic, Rajko; Demirozu, Zumrat T; Frazier, O H; Buja, L Maximilian

    2015-04-01

    Nonischemic cardiomyopathy can complicate antineoplastic therapy and lead to irreversible heart failure. We evaluated structural changes at the time of left ventricular assist device implantation in heart failure patients who had been exposed to anthracycline, and we correlated those changes with clinical presentation. We retrospectively studied left ventricular core samples taken at implantation of the HeartMate II left ventricular assist device in 12 heart failure patients (mean age, 46 ± 16 yr) who had histories of anthracycline exposure. We evaluated those samples for hypertrophy, myocytolysis, and fibrosis. Histopathologic findings showed moderate-to-severe myocyte hypertrophy, moderate myocytolysis, and perivascular and interstitial fibrosis with areas of replacement fibrosis. Ultrastructural studies revealed marked decreases in myofibrils, diffuse mitochondrial swelling, and disorganization of the sarcoplasmic reticulum. The interval between anthracycline therapy and heart failure was a mean of 6.8 ± 5.7 years; duration of heart failure symptoms, 38 ± 47 months; and duration of device support, 414 ± 266 days. Four patients are continuing on device support, 3 have undergone transplantation, 3 have undergone device explantation, and 2 have died. The time of heart failure onset and the duration of symptoms did not correlate with the severity and extent of the histopathologic changes. The histopathologic findings and the clinical course varied in heart failure patients with anthracycline exposure. No correlation was observed between anthracycline therapy and the development or duration of heart failure symptoms, severity of histopathologic changes, or outcomes. PMID:25873821

  18. Towards a re-definition of 'cardiac hypertrophy' through a rational characterization of left ventricular phenotypes: a position paper of the Working Group 'Myocardial Function' of the ESC.

    OpenAIRE

    TARONE, Guido

    2011-01-01

    Many primary or secondary diseases of the myocardium are accompanied with complex remodelling of the cardiac tissue that results in increased heart mass, often identified as cardiac 'hypertrophy'. Although there have been numerous attempts at defining such 'hypertrophy', the present paper delineates the reasons as to why current definitions of cardiac hypertrophy remain unsatisfying. Based on a brief review of the underlying pathophysiology and tissue and cellular events driving myocardial re...

  19. Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension

    Directory of Open Access Journals (Sweden)

    Ernesto Germán Cardona-Muñoz

    2007-09-01

    Full Text Available Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC, were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0 and post-glucose challenge levels (rG/I: Group 1 (normoinsulinemic patients I0 2 (2.45+0.4. Group 2 (post-prandial hyperinsulinemic patients I0 17 mU/mL and <1 (0.7+0.3. Left ventricular mass and its diastolic function were measured by Doppler echocardiography. Results: No differences in blood pressure or age were observed between groups. There was a negative correlation between ventricular mass and rG/1 (r =-0.282, p =0.015. Left ventricular diastolic dysfunction was significantly more deteriorated in group 3, as compared with group 1 (p <0.001 ANOVA. There was a significant correlation between g/GI and diastolic dysfunction (r =0.232 p =0.047. Conclusions: Fasting, post challenge hyperinsulinemia and a rG/I <1 are associated with higher ventricular mass and left ventricular diastolic dysfunction, independent of blood pressure and age (Rev Méd Chile 2007; 135: 1125-31

  20. Basal Septal Hypertrophy

    OpenAIRE

    Kelshiker, Mihir A.; Mayet, Jamil; Unsworth, Beth; Okonko, Darlington O.

    2013-01-01

    A significant clinical problem is patients presenting with exercise-limiting dyspnoea, sometimes with associated chest pain, in the absence of detectable left ventricular (LV) systolic dysfunction, coronary artery disease, or lung disease. Often the patients are older, female, and have isolated basal septal hypertrophy (BSH), frequently on a background of mild hypertension. The topic of breathlessness in patients with clinical heart failure, but who have a normal ejection fraction...

  1. Índice tornozelo-braquial e hipertrofia ventricular na hipertensão arterial Índice tobillo-braquial y hipertrofia ventricular en la hipertensión arterial Ankle-brachial index and ventricular hypertrophy in arterial hypertension

    OpenAIRE

    Pedro Ferreira de Albuquerque; Pedro Henrique Oliveira de Albuquerque; Gustavo Oliveira de Albuquerque; Denise Maria Servantes; Saskya Meneses de Carvalho; Japy Angelini Oliveira Filho

    2012-01-01

    O Índice Tornozelo-Braquial (ITB) é marcador de doença arterial obstrutiva periférica. Raros relatos correlacionam esse índice com hipertrofia ventricular esquerda (HVE), capacidade funcional (CF) e escore de risco coronariano de Framingham (ERCF). O objetivo do trabalho foi verificar a correlação entre ITB, HVE, CF e ERCF em homens com hipertensão arterial (HA). Estudo prospectivo e transversal de pacientes do sexo masculino (n = 40), com idade média de 57,92 ± 7,61 anos, sem compl...

  2. Impact of alcohol habits and smoking on the risk of new-onset atrial fibrillation in hypertensive patients with ECG left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Ariansen, Inger; Reims, Henrik M

    2012-01-01

    Abstract Background. The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF. However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment. Methods. In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double-blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol-based antihypertensive therapy were followed for a mean of 4.8 years. At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study. Results. New-onset AF occurred in 353 (4%) patients. Univariate Cox analyses showed that intake of alcohol > 10 units/week compared with less or no alcohol intake predicted new-onset AF (Hazard ratio, HR = 1.60 [95% CI 1.02-2.51], p = 0.043). Multivariate Cox regression analysis showed that intake of alcohol > 10 units/week predicted new-onset AF (p = 0.010) independently of most other univariate predictors, except when also baseline serum cholesterol, serum potassium and urinary albumin/creatinine ratio were included in the model (HR = 1.60 [95% CI 0.94-2.72], p = 0.081). Impact of smoking was not significant in Cox univariate or multivariate analyses, and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF. Conclusions. Up to 10 drinks of alcohol per week appears to be safe with respect to the risk for AF in hypertensive patients with LVH. Our data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH.

  3. Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients with Aortic Stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis Study

    DEFF Research Database (Denmark)

    Greve, Anders; Boman, Kurt

    2012-01-01

    BACKGROUND: The prognostic impact of electrocardiographic left ventricular (LV) strain and hypertrophy (LVH) in asymptomatic aortic stenosis (AS) is not well described. METHODS AND RESULTS: Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary endpoint was the first of myocardial infarction, non-hemorrhagic stroke, heart failure, aortic valve replacement (AVR) or cardiovascular death. Predictive value of electrocardiographic LV strain (defined as T-wave inversion in leads V(4-6)) and LVH (assessed by Sokolow-Lyon voltage criterion (R(V5-6)+S(V1) ?35 mV) and Cornell voltage-duration criteria ((RaVL+S(V3)+[6 mV in women]) × QRS-duration ?2440 mV msec), was evaluated by adjusting for other prognostic covariates. 1,533 patients were followed 4.3±0.8 years (6,592 patient-years of follow-up), 627 cardiovascular events occurred. Electrocardiographic strain was present in 340 (23.6%) patients; LVH by Sokolow-Lyon voltage in 260 (17.1%) and in 220 (14.6%) by Cornell voltage-duration product. In multivariable analyses, electrocardiographic LV strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval [CI], 1.4 to 6.8, p=0.004). Similarly, electrocardiographic LVH by both criteria predicted, compared to no electrocardiographic LVH, 5.8-fold higher risk of heart failure (95% CI, 2.0 to 16.8), 2.0-fold higher risk of AVR (95% CI, 1.3 to 3.1, both p=0.001) and 2.5-fold higher risk of a combined endpoint of myocardial infarction, heart failure or cardiovascular death (95% CI, 1.3 to 4.9, p=0.008). CONCLUSIONS: Electrocardiographic LV strain and LVH were independently predictive of poor prognosis in asymptomatic AS. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov; NCT00092677.

  4. Tetrahydrobiopterin reverse left ventricular hypertrophy and diastolic dysfunction through the PI3K/p-Akt pathway in spontaneously hypertensive rats.

    Science.gov (United States)

    Chang, Peng; Wang, Qiongying; Xu, Han; Yang, Mina; Lin, Xin; Li, Xiuli; Zhang, Zhengyi; Zhang, Xiaowei; Zhao, Feng; Zhao, Xu; Bai, Feng; Yu, Jing

    2015-08-01

    Hypertension induced hypertrophy and diastolic dysfunction and is associated with cardiac oxidation and reduced NO production. We hypothesized that tetrahydrobiopterin (BH4) can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and reverse cardiac hypertrophy and diastolic dysfunction in spontaneously hypertensive rats. Ten-week-old male spontaneously hypertensive rats (SHR) and age-matched normotensive control Wistar-Kyoto (WKY) rats were divided into five groups, WKY, WKY + BH4, SHR, SHR + BH4 and SHR + VAL. In SHR, diastolic dysfunction was accompanied by concentric hypertrophy, cardiac oxidation, and reduced cardiac BH4 and NO production. Four-week BH4 and valsartan administration reversed hypertrophy and improved diastolic function. BH4 and valsartan blunted the expression of hypertrophy markers ?-skeletal actin (?-SA) and ?-myosin heavy chain (?-MHC). Only BH4 reduced hypertension and induced myocardial fibrosis and expression of transforming growth factor-?1 (TGF-?1). BH4 reduced cardiac oxidant stress and increased NO production. Exogenous BH4 increased phosphorylated Akt levels and increased Bcl-2 expression. In conclusion, less BH4 and reduced NO increases myocardial hypertrophy and cardiac oxidative stress, which exacerbates diastolic dysfunction. Exogenous BH4 ameliorates cardiac hypertrophy and diastolic dysfunction through the PI3K/p-Akt pathway. BH4 may be a potent therapy for hypertension with diastolic dysfunction. PMID:26093301

  5. Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis

    International Nuclear Information System (INIS)

    Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with [3H]thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other handss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss

  6. Comparison of formaldehyde and methanol fixatives used in the detection of ion channel proteins in isolated rat ventricular myocytes by immunofluorescence labelling and confocal microscopy.

    Science.gov (United States)

    Yamanushi, T T; Boyett, M R; Yamamoto, Y; Ohsaki, H; Hirakawa, E; Dobrzynski, H

    2015-01-01

    In this study, a fixation protocol using a 10% neutral buffered formalin (FA) solution and another protocol using a methanol (MeOH) solution were compared for detection of ion channels, Kv1.5, Kv4.2, Cav1.2, Kir6.2, Nav1.5 and Nav1.1 in rat myocytes by immunolabelling. Kv1.5 and Kv4.2 at intercalated discs and Cav1.2 at transverse tubules were not detected by FA but were detected by MeOH. Kir6.2 at transverse tubules and Nav1.5 at sarcolemma were detected by FA but not by MeOH. It is suggested that both FA and MeOH fixation protocols should be used for the detection of cardiac ion channels by immunolabelling. PMID:26050816

  7. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes.

    OpenAIRE

    Shubeita, H E; Martinson, E A; Bilsen, M. van; Chien, K. R.; J.H. Brown

    1992-01-01

    A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during alpha-adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the alpha-adrenergic agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/lu...

  8. Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    M.A. Carneiro-Júnior

    2010-11-01

    Full Text Available We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR randomly divided into the following groups: sedentary for 8 weeks (SED-8, sedentary for 12 weeks (SED-12, treadmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week, and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET. At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 ?m, P < 0.05, 667 vs 618 cells, respectively and remained larger after detraining. Cell width and volume were unaffected by either exercise training or detraining. Cell length to width ratio was higher in TRA than in SED-8 (8.50 ± 0.08 vs 8.22 ± 0.10, P < 0.05 and was maintained after detraining. Exercise training did not affect cell shortening, which was unchanged with detraining. TRA cells exhibited higher maximum velocity of shortening than SED-8 (102.01 ± 4.50 vs 82.01 ± 5.30 ?m/s, P < 0.05, 70 cells per group, with almost complete regression after detraining. The maximum velocity of relengthening was higher in TRA cells than in SED-8 (88.20 ± 4.01 vs70.01 ± 4.80 ?m/s, P < 0.05, returning to sedentary values with detraining. Therefore, exercise training affected left ventricle remodeling in SHR towards eccentric hypertrophy, which remained after detraining. It also improved single left ventricular myocyte contractile function, which was reversed by detraining.

  9. The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy

    Science.gov (United States)

    Sadoshima, Junichi; Montagne, Olivier; Wang, Qian; Yang, Guiping; Warden, Jill; Liu, Jing; Takagi, Gen; Karoor, Vijaya; Hong, Chull; Johnson, Gary L.; Vatner, Dorothy E.; Vatner, Stephen F.

    2002-01-01

    Mitogen-activated protein kinase kinase kinase (MEKK1) mediates activation of c-Jun NH2-terminal kinase (JNK). Although previous studies using cultured cardiac myocytes have suggested that the MEKK1-JNK pathway plays a key role in hypertrophy and apoptosis, its effects in cardiac hypertrophy and apoptosis are not fully understood in adult animals in vivo. We examined the role of the MEKK1-JNK pathway in pressure-overloaded hearts by using mice deficient in MEKK1. We found that transverse aortic banding significantly increased JNK activity in Mekk1+/+ but not Mekk1–/– mice, indicating that MEKK1 mediates JNK activation by pressure overload. Nevertheless, pressure overload caused significant levels of cardiac hypertrophy and expression of atrial natriuretic factor in Mekk1–/– animals, which showed higher mortality and lung/body weight ratio than were seen in controls. Fourteen days after banding, Mekk1–/– hearts were dilated, and their left ventricular ejection fraction was low. Pressure overload caused elevated levels of apoptosis and inflammatory lesions in these mice and produced a smaller increase in TGF-? and TNF-? expression than occurred in wild-type controls. Thus, MEKK1 appears to be required for pressure overload–induced JNK activation and cytokine upregulation but to be dispensable for pressure overload–induced cardiac hypertrophy. MEKK1 also prevents apoptosis and inflammation, thereby protecting against heart failure and sudden death following cardiac pressure overload. PMID:12122119

  10. Tanshinone IIA Protects Against Cardiac Hypertrophy via Inhibiting Calcineurin/Nfatc3 Pathway

    Directory of Open Access Journals (Sweden)

    Xueying Tan, Jianping Li, Xinyue Wang, Nan Chen, Benzhi Cai, Gang Wang, Hongli Shan, Deli Dong, Yanju Liu, Xingda Li, Fan Yang, Xin Li, Peng Zhang, Xueqi Li, Baofeng Yang, Yanjie Lu

    2011-01-01

    Full Text Available Pathological cardiac hypertrophy induced by adrenergic overactivation can subsequently develop to heart failure which remains as a leading cause of mortality worldwide. Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. However, little is know about the effect of Tanshinone IIA on cardiac hypertrophy. The present study was aimed to investigate whether Tanshinone IIA prevents cardiac hypertrophy induced by isoproterenol (ISO and to clarify its possible mechanisms. Cardiomyocytes hypertrophy was induced by ISO 10 ?M for 48 h with or without Tanshinone IIA 10, 30, 100 ?M pretreatment, and evaluated by determining the cell size and the expression of ANP, BNP, ?-MHC, Calcineurin, and NFATc3 by real-time PCR and western blot. We found that Tanshinone IIA pretreatment attenuated the enlargement of cell surface area induced by ISO in cultured cardiomyocytes. The mRNA level of ANP, BNP and ?-MHC was obviously elevated in ISO-treated cardiac cells, which was effectively inhibited by Tanshinone IIA. Moreover, we found that Tanshinone IIA pretreatment could prevent the augment of intracellular calcium transient in ISO-treated cardiomyocytes. The further study revealed that Calcineurin, NFATc3, ANP, BNP and ?-MHC proteins were upregulated by ISO in ventricular myocytes, and Tanshinone IIA pretreatment significantly attenuate the increased expression of Calcineurin, NFATc3, ANP, BNP and ?-MHC proteins. In summary, Tanshinone IIA attenuated cardiomyocyte hypertrophy induced by ISO through inhibiting Calcineurin/NFATc3 pathway, which provides new insights into the pharmacological role and therapeutic mechanism of Tanshinone IIA in heart diseases.

  11. Tratamiento con eritropoyetina recombinante humana, hipertrofia ventricular izquierda y balance beneficio riesgo en la ERC-3b / Treatment with recombinant erythropoietin, left ventricular hypertrophy and balance benefit-risk in CKD-3b

    Scientific Electronic Library Online (English)

    Jorge F, Pérez-Oliva Díaz; Martha, Casanova González; Orosmán, Cuesta Panaco; Osniel, Bencomo Rodríguez; Beatriz, López Tórres; Claudio, González; Liván, Cruz Benítez; Idrian, García García; Ángela D, Tuero Iglesias; Carmen M, Valenzuela Silva; Pedro A, López Saura.

    2013-09-01

    Full Text Available Introducción: la anemia renal es frecuente en la enfermedad renal crónica avanzada (ERC 3b-4) y el tratamiento con eritropoyetina recombinante humana la mejora pero aún está a debate cual meta de hemoglobina alcanzar y cuál es su repercusión sobre las funciones cardíacas. Objetivo de este trabajo fu [...] e evaluar la mejoría de la anemia tratada con EPOrHu sobre parámetros de la función cardiovascular ventricular izquierda en la ERC 3b-4 y el riesgo beneficio. Material y métodos: ensayo clínico abierto, no controlado, no aleatorizado, multicéntrico, prospectivo, seguimiento durante 56 semanas de seguimiento. Se evalúan los cambios en la Tasa de Filtración Glomerular por la fórmula del MDRD y por ecocardiografía en relación al nivel basal, al final del seguimiento estimada la variación al año de la HVI. Resultados: se observó un incremento significativo del hematócrito en todos los pacientes al final del estudio (n = 33, 0.29 ± 0,02 (V%) versus 0.38 ± 0.03, P (Wilcoxon)= 0.000. Al eco inicial el 90,9% tenían HVI y al final solo el 78.8% con una disminución de 2.2 mm (14 a 11.8 mm), y una correlación inversa lineal entre la HVI y la mejoría de la hemoglobina (r = -0.379; p = 0.030). La progresión del daño renal fue lenta (mL/min). En los pacientes diabéticos de 37.2 ± 8.4 versus 34.7 ± 6.7, (p Wilcoxon=0.119) y en los no diabéticos de 35.1 ± 7.833.6 ± 7.7 (p Wilcoxon= 0.119). El 48.5% de los pacientes presentaron algún tipo de evento adverso, ninguno falleció o comenzó hemodiálisis durante el seguimiento. El Balance Beneficio- Riesgo (EA moderados o graves) estimados por el cálculo del Factor de Bayes fue a favor del Beneficio (FB=1,5). Conclusiones: la corrección de la anemia renal en pacientes con ERC-3b con EPOrHu cubana mejora la HVI sin provocar otros daños Este trabajo apoya el tratamiento de la anemia severa con EPOrHU. Abstract in english Introduction: renal anemia is a frequent complication among patients with chronic kidney disease (CKD). The introduction of recombinant erythropoietin (rhuEpo) treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its eff [...] ect on cardiac functions is in discussion. Objective: this study aimed to explore the effect of pre-dialysis erythropoiesis-stimulating agent (ESA) use on the left ventricular hypertrophy (LVH) or general and renal function protective effect in CKD3b-4 patients. Different than in introducción in Spanish. Patients and methods: open multicentric assay. A 56-week follow-Up dose-response study. The change from baseline to the end of treatment was calculated for glomerular filtration rate by MDRD (GFR,) and, LVH by echocardiography at 24 months. Results: the treatment significantly increased hematocrit (Htc) in all patients who completed the study (n = 33, 0.29 ± 0.02(V%) versus 0.38 ± 0.03, P (Wilcoxon)= 0.000. In the beginning 90,9% At the end only the 78.8% the patients had LVH, it was decreased 2.2 mm (14 a 11.8 mm), and significant reverse lineal correlation between the change in the LVH and Hb concentration was noted (r = -0.379; p = 0.030). Progression of the CKD was slow (mL/min). Diabetics 37.2 ± 8.4 versus 34.7 ± 6.7 (p Wilcoxon=0.119) non diabetics 35.1 ± 7.833.6 ± 7.7 (p Wilcoxon= 0.119). 48.5% of the patients had Adverse effects (AE). No patients died or started in dialysis. The Balance Benefit- Risk (AE moderate or severe) estimated from the Bayes Factor was evidence to the benefit (BF=1, 64). Conclusion: we observed that correction of anemia with rhuEpo in patients with CKD 3b seems to improve the LVH without another problems and it is beneficial. The results of this study support the treatment of severe anemia with EPO.

  12. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.

    OpenAIRE

    Simpson, P.

    1983-01-01

    We have shown recently that norepinephrine stimulates muscle cell hypertrophy in primary cultures from the neonatal rat ventricle and that this stimulation is not blocked by the beta adrenergic antagonist propranolol. The present study was done to define the adrenergic specificity of the myocyte hypertrophic response to norepinephrine. 90% pure, single-cell cultures of nongrowing myocytes were maintained in serum-free medium 199 with transferin and insulin. Myocyte size was quantitated 48 h a...

  13. Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension

    Scientific Electronic Library Online (English)

    Ernesto Germán, Cardona-Muñoz; David, Cardona-Müller; Sylvia, Totsuka-Sutto; Carlos Martín, Nuño-Guzmán; Sara, Pascoe-González; Marina, Romero-Prado; Alejandra G, Miranda-Díaz.

    1125-11-01

    Full Text Available [...] Abstract in english Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four [...] patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and

  14. The clinical value of apex beat and electrocardiography for the detection of left ventricular hypertrophy from the standpoint of the distance factors from the heart to the chest wall. A multislice CT study

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the clinical value of the apex beat and two electrocardiographic (ECG) voltage criteria in the detection of left ventricular hypertrophy (LVH) while considering two distances, from the heart to the inner chest wall and to the chest surface, measured by using multislice CT (MSCT). The study population consisted of 151 patients clinically judged as requiring MSCT angiography. The apex beat was palpated with patients in the supine. Sokolow-Lyon voltage and Cornell voltage to detect LVH were determined. The pattern of sustained or double apical impulse and Cornell voltage had higher specificity as an indicator of LVH than Sokolow-Lyon voltage. Furthermore, the distance to the inner chest wall was negatively correlated with left ventricular end-diastolic volume and mass. Contrarily, the distance to the chest surface was correlated with the body mass index. Multivariate analyses revealed that the pattern of sustained or double apical impulse showed a stronger association with the distance to the inner chest wall than to the chest surface, but Sokolow-Lyon voltage was associated with the distance to the chest surface. Among the screening tests for excluding patients with LVH, Cornell voltage or the apex beat would be better than Sokolow-Lyon voltage because these are less dependent on body size and have higher specificity. (author)

  15. Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms / Efeito da denervação renal na hipertrofia do ventrículo esquerdo de ratos hipertensos e seu mecanismo

    Scientific Electronic Library Online (English)

    Weihong, Jiang; Lihua, Tan; Yunzhong, Guo; Xiaogang, Li; Xiaohong, Tang; Kan, Yang.

    2012-11-01

    Full Text Available OBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D) [...] e grupo sham(S). 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI). RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p Abstract in english PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-?B in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group [...] (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-?B, TNF-? and IL-6 in the myocardium were markedly higher than that in the WKY group (p

  16. Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-?B/PGC-1? Signaling Mediated Energy Biosynthesis

    Science.gov (United States)

    Yang, Yuhong; Lu, Meili; Luan, Aina; Zhang, Jing; Yang, Juan; Wang, Hongxin

    2015-01-01

    We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor ?B (NF-?B)/Peroxisome Proliferator-Activated Receptor-? Coactivator 1? (PGC-1?) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-?B/PGC-1? signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1?, inhibited translocation of p65, subunit of NF-?B into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1? expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-?B/PGC-1? signaling mediated energy biosynthesis. PMID:25738576

  17. The eIF2B-interacting domain of RGS2 protects against GPCR agonist-induced hypertrophy in neonatal rat cardiomyocytes.

    Science.gov (United States)

    Chidiac, Peter; Sobiesiak, Alina J; Lee, Katherine N; Gros, Robert; Nguyen, Chau H

    2014-06-01

    The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac hypertrophy is thought to occur through its ability to inhibit the chronic GPCR signaling that promotes pathogenic growth both in vivo and in cultured cardiomyocytes. However, RGS2 is known to have additional functions beyond its activity as a GTPase accelerating protein, such as the ability to bind to eukaryotic initiation factor, eIF2B, and inhibit protein synthesis. The RGS2 eIF2B-interacting domain (RGS2(eb)) was examined for its ability to regulate hypertrophy in neonatal ventricular myocytes. Both full-length RGS2 and RGS2(eb) were able to inhibit agonist-induced cardiomyocyte hypertrophy, but RGS2(eb) had no effect on receptor-mediated inositol phosphate production, cAMP production, or ERK 1/2 activation. These results suggest that the protective effects of RGS2 in cardiac hypertrophy may derive at least in part from its ability to govern protein synthesis. PMID:24576550

  18. Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms Efeito da denervação renal na hipertrofia do ventrículo esquerdo de ratos hipertensos e seu mecanismo

    Directory of Open Access Journals (Sweden)

    Weihong Jiang

    2012-11-01

    Full Text Available PURPOSE: To investigate the effect of renal denervation (RDN on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-?B in spontaneously hypertensive rats (SHR. METHODS: A total of 36 SHR were randomly assigned into control group (D0, RDN group (D and sham group (S. 12 WKY rats of same age served as controls (WKY group. Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI. RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-?B, TNF-? and IL-6 in the myocardium were markedly higher than that in the WKY group (pOBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D e grupo sham(S. 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI. RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p<0,05. Nos grupos D1 e D2, o LVMI, NE e a expressão proteica de TLR4, NF-?B, TNF-? e IL-6 no miocárdio foi significantemente reduzido (p<0,05. CONCLUSÃO: A denervação renal pode significantemente retardar a progressão da hipertrofia ventricular esquerda em ratos espontaneamente hipertensos, o que pode ser atribuído não apenas pela supressão da atividade simpática e atenuação da pressão, mas pela melhora na imunoinflamação miocárdica.

  19. Cytosolic CARP Promotes Angiotensin II- or Pressure Overload-Induced Cardiomyocyte Hypertrophy through Calcineurin Accumulation

    Science.gov (United States)

    Chen, Ci; Shen, Liang; Cao, Shiping; Li, Xixian; Xuan, Wanling; Zhang, Jingwen; Huang, Xiaobo; Bin, Jianping; Xu, Dingli; Li, Guofeng; Kitakaze, Masafumi; Liao, Yulin

    2014-01-01

    The gene ankyrin repeat domain 1 (Ankrd1) is an enigmatic gene and may exert pleiotropic function dependent on its expression level, subcellular localization and even types of pathological stress, but it remains unclear how these factors influence the fate of cardiomyocytes. Here we attempted to investigate the role of CARP on cardiomyocyte hypertrophy. In neonatal rat ventricular cardiomyocytes (NRVCs), angiotensin II (Ang II) increased the expression of both calpain 1 and CARP, and also induced cytosolic translocation of CARP, which was abrogated by a calpain inhibitor. In the presence of Ang-II in NRVCs, infection with a recombinant adenovirus containing rat Ankrd1 cDNA (Ad-Ankrd1) enhanced myocyte hypertrophy, the upregulation of atrial natriuretic peptide and ?-myosin heavy chain genes and calcineurin proteins as well as nuclear translocation of nuclear factor of activated T cells. Cyclosporin A attenuated Ad-Ankrd1-enhanced cardiomyocyte hypertrophy. Intra-myocardial injection of Ad-Ankrd1 in mice with transverse aortic constriction (TAC) markedly increased the cytosolic CARP level, the heart weight/body weight ratio, while short hairpin RNA targeting Ankrd1 inhibited TAC-induced hypertrophy. The expression of calcineurin was also significantly increased in Ad-Ankrd1-infected TAC mice. Olmesartan (an Ang II receptor antagonist) prevented the upregulation of CARP in both Ang II-stimulated NRVCs and hearts with pressure overload. These findings indicate that overexpression of Ankrd1 exacerbates pathological cardiac remodeling through the enhancement of cytosolic translocation of CARP and upregulation of calcineurin. PMID:25089522

  20. mTOR mediates RhoA-dependent leptin-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Zeidan, Asad; Hunter, J Craig; Javadov, Sabzali; Karmazyn, Morris

    2011-06-01

    Obesity is associated with increased leptin production which may contribute to cardiac hypertrophy. However, the mechanism of leptin-induced cardiac hypertrophy remains incompletely understood. The Rho family (RhoA, Rac1, and Cdc42) and mammalian target of rapamycin (mTOR) have recently emerged as important regulators of cell growth. We therefore explored the roles and interrelationships of phosphatidylinositol 3-kinase (PI3K), mTOR, and the Rho family in the regulation of actin polymerization and leptin-induced hypertrophy in cultured neonatal rat ventricular myocytes. Five minutes treatment with leptin (3.1 nM) resulted in activation of RhoA and Rac1 (by 330 and 160%, respectively, P < 0.05) which was significantly attenuated by AG-490 (50 ?M) and LY294002 (10 ?M), specific inhibitors of JAK2 and PI3K, respectively. However, Cdc42 activity was unaffected by leptin. The hypertrophic effect of leptin was associated with an increase in phosphorylation of p70(S6K), the major target of mTOR, by 110% (P < 0.05). The specific mTOR inhibitor rapamycin (10 nM) attenuated leptin-induced RhoA and Rac1 activation. Furthermore, the leptin-induced decrease in the G/F-actin ratio, a measure of actin polymerization, was blunted by rapamycin. Leptin produced activation of the transcriptional factor GATA4 which was attenuated by the RhoA inhibitor C3, the p38 MAPK inhibitor SB203580 (10 ?M) as well as rapamycin. Our results demonstrate a critical role for PI3K/mTOR/p70(S6K) in leptin-induced RhoA activation resulting in cardiomyocyte hypertrophy associated with GATA4 stimulation. PMID:21318349

  1. Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs

    DEFF Research Database (Denmark)

    Smith, Julie; Goetze, Jens Peter

    2012-01-01

    BACKGROUND: Patients may suffer from right ventricular (RV) failure and malignant cardiac arrhythmias after late pulmonary valve replacement correcting pulmonary regurgitation (PR). But the underlying mechanisms of the refractory arrhythmias are not well understood. METHODS: The aim of present study was to characterize the RV myocardium after percutaneous pulmonary valve implantation (PPVI) in a porcine model after severe PR for 3months. RV histology was evaluated with morphometric methods and RV function was assessed with electrophysiology, echocardiography, and biochemical measures: The results were compared with age-matched sham-operated animals. RESULTS: At euthanasia, RV weight was increased compared to sham-animals, median 127g (115-137) vs. 71g (69.5-76.5), p=0.0007. RV myocyte diameters corrected for individual variation with the RV/LV ratio were enlarged, 1.06 (1.02-1.13) vs. 0.84 (0.80-0.91), p=0.0006. There were no excess collagen tissue (RV/LV ratio), p=0.77. Electrophysiological stimulation resulted in RV arrhythmia in 67% of the animals compared to 25% in the sham-operated animals, but this difference was not statistically significant, p=0.28. Echocardiography revealed geometrical dilation in end-systolic RV area, mean±SD, 11.8±4.9cm(2) vs. 6.0±3.5cm(2), p=0.05, and end-diastolic area, 23.3±10.4cm(2) vs. 12.7±2.5cm(2), p=0.08. RV anterior free wall thickness was not increased, 0.7±0.2cm vs. 0.7±0.1cm, p=0.66. Echocardiographic functional parameters and plasma natriuretic peptides were unchanged. CONCLUSIONS: The RV does not completely recover after three months of PR with persistent myocardial hypertrophy one month after PPVI. Future studies should address whether RV chamber and cellular hypertrophy, without fibrosis or interventional scar tissue, may be substrate for arrhythmia.

  2. Cardiac Nonmyocytes in the Hub of Cardiac Hypertrophy.

    Science.gov (United States)

    Kamo, Takehiro; Akazawa, Hiroshi; Komuro, Issei

    2015-06-19

    Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of myocytes and nonmyocytes, such as fibroblasts, vascular cells, and blood cells, and these cells communicate with each other directly or indirectly via a variety of autocrine or paracrine mediators. Accumulating evidence has suggested that nonmyocytes actively participate in the development of cardiac hypertrophy. In this review, recent progress in our understanding of the importance of nonmyocytes as a hub for induction of cardiac hypertrophy is summarized with an emphasis of the contribution of noncontact communication mediated by diffusible factors between cardiomyocytes and nonmyocytes in the heart. PMID:26089366

  3. Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice

    OpenAIRE

    Cha, Hye-na; Choi, Jung Hyun; Kim, Yong-woon; Kim, Jong-yeon; Ahn, Myun-whan; Park, So-young

    2010-01-01

    The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-?, atrial natriuretic peptide (ANP), collagen I and III, ...

  4. Estudio de la función ventricular y su correlación con la morfometría en pacientes con estenosis aórtica grave sintomática / Relationship of Ventricular Function and Morphometry in Patients with Symptomatic Aortic Stenosis

    Scientific Electronic Library Online (English)

    Alejandro, Hita; Martín, Donato; Sergio, Baratta; Demián, Chejtman; Ricardo A., Costantini; Juan M., Telayna; Mirian, Matoso; Celina, Morales; Ricardo J., Gelpi; José, Navia.

    2011-08-01

    Full Text Available Introducción En la estenosis aórtica, el mecanismo de adaptación miocárdica a la sobrecarga de presión es la hipertrofia ventricular. Diferentes trabajos han planteado la correlación entre estructura y función en la sobrecarga de presión por estenosis aórtica y su posible asociación con la evolución [...] de la patología ventricular. Sin embargo, son escasos los trabajos en los que se evalúan estas variables en corazones con hipertrofia ventricular compensada (sin incremento significativo del estrés parietal) y con fracción de eyección conservada. Objetivos Evaluar la función ventricular sistólica y diastólica en pacientes con estenosis aórtica grave sintomática con fracción de eyección conservada y correlacionarla con el volumen de colágeno y el área miocitaria. Material y métodos Se estudiaron 12 pacientes, edad 65 ± 13 años, sexo masculino 58%, con estenosis aórtica grave sintomática y 6 pacientes sin patología valvular. En todos se realizaron Doppler tisular y cateterismo cardíaco; asimismo, se efectuaron biopsias intraoperatorias para determinar el volumen de colágeno y el área miocitaria (µm²). Resultados La media ± error estándar del volumen de colágeno fue del 6,1% ± 0,7%, la del área miocitaria fue de 388,4 ± 15,8 µm² y la mediana del strain tisular del septum basal fue del 14% (IIC 6,9-19). Se observó una correlación significativa entre el strain tisular del septum y el volumen de colágeno (coeficiente de correlación de -0,79; p = 0,03). No se observó correlación entre el strain tisular del septum y el área miocitaria (R² = 0,15; p = 0,8). La +dP/dt máx normalizada por presión de fin de diástole del ventrículo izquierdo obtenida en estudio hemodinámico se correlacionó en forma negativa con el área miocitaria (R -0,94; p = 0,005). La constante de caída de la presión (tau) se incrementó el 55% ± 3,5% (p Abstract in english Background Ventricular hypertrophy is an adaptive mechanism of the myocardium to pressure overload in aortic stenosis. Different studies have postulated a correlation between structure and function in pressure overload due to aortic stenosis and the possible association with the development of patho [...] logical ventricular growth. However, there are a few studies evaluat-ing these variables in hearts with compensated ventricular hypertrophy (without a significant increase in wall stress) and preserved ejection fraction. Objectives To evaluate systolic and diastolic ventricular function in patients with symptomatic severe aortic stenosis with preserved ejection fraction and its correlation with collagen volume fraction and myocyte cross-sectional area. Material and Methods A total of 12 patients with symptomatic severe aortic stenosis were evaluated and compared with 6 patients without valvular heart disease; mean age was 65±13 years and 58% were men. All patients underwent tissue Doppler imaging and cardiac catheterization. Endomyocardial biopsies were obtained to determine collagen volume fraction and myocyte cross-sectional area (µm²). Results Mean collagen volume was 6.1±0.7%; mean myocyte cross-sectional area was 388.4±15.8 µm² and median strain in the basal septum was 14% (IIC 6.9-19). There was a significant correlation between septal strain measured by tissue Doppler imaging and collagen volume fraction (correlation coefficient -0.79; p = 0.03). We found no correlation between septal strain and myocyte cross-sectional area (R² = 0.15; p = 0.8). The max positive dP/dt normalized for left ventricular end-diastolic pressure obtained during cardiac catheterization had a negative correlation with the myocyte cross-sectional area (R -0.94; p = 0.005).The time constant of pressure decay (tau) increased by 55%±3,5% (p

  5. pH regulation in adult cardiac myocytes

    International Nuclear Information System (INIS)

    The purpose of this study is to examine the pHi regulatory mechanisms of adult ventricular myocytes, the cells that perform the pumping work of the heart. The cell system for this study was the ventricular myocyte, isolated by enzymatic dissociation from adult rate heart. In agreement with the findings on other cardiac model cells, I demonstrated the existence of a Cl-/HCO3- exchanger and a Na+/H+ exchanger in ventricular myocytes. The existence of the anion exchanger was demonstrated in 36Cl- flux experiments and as stilbene disulfonate-inhibitable and Cl- gradient-dependent intracellular pH shifts in the presence of bicarbonate. The fluorescein derivative BCECF served as a fluorescent probe of intracellular pH in the these experiments. The existence of the Na+/H+ exchanger was demonstrated in pHi experiments using BCECF. Further experiments characterized the kinetics of the Na+/H+ exchanger and its regulation. The steady-state pHi of ventricular myocytes was 7.16 ± 0.11 at pH0 = 7.4. Several agonists caused a rise in steady-state pHi: the protein kinase stimulator phorbol myristate acetate (PMA), the ?1-adrenergic agonist 6-fluoro-norepinephrine (6F-NE) and the ?-agonist UK14304, and ATP

  6. Frecuencia y factores de riesgo de la hipertrofia ventricular izquierda como marcador de daño cardiovascular en el trasplante renal / Frequency and risk factors of the left ventricular hypertrophy like scoreboard of cardiovascular damage in renal transplant

    Scientific Electronic Library Online (English)

    Gerardo, Borroto Díaz; Haruka, Tsuno López; Oyantay, Mérida Álvarez; Carlos, Guerrero Díaz; Malicela, Barceló Acosta.

    2012-06-01

    Full Text Available Introducción: las complicaciones cardiovasculares son frecuentes y constituyen la principal causa de muerte en los pacientes con trasplantes renales, su alta incidencia está dada por múltiples factores de riesgo. Objetivos: determinar la frecuencia de la hipertrofia del ventrículo izquierdo como mar [...] cador de daño cardiovascular, y los factores de riesgo que facilitarían su aparición. Métodos: se hizo un estudio prospectivo, de corte transversal y de tipo casos y controles, a 70 enfermos con trasplantes renales a los cuales se les realizó un ecocardiograma convencional para determinar la presencia o no de hipertrofia del ventrículo izquierdo y se relacionó, mediante un estudio univariado y multivariado (regresión logística), con factores de riesgo cardiovascular. Resultados: las afecciones cardiovasculares constituyeron la segunda causa de pérdida de los pacientes en este estudio (33,1 %), La hipertrofia del ventrículo izquierdo se encontró en 45 (64 %) de los enfermos pesquisados. La dislipemia, el uso de la ciclosporina A y la disfunción del injerto, fueron las complicaciones que constituyeron, tanto en el estudio univariado como multivariado (factor independiente), p Abstract in english Introduction: the cardiovascular complications are frequent and are the leading cause of death in patients underwent renal transplantation and its high incidence is due to multiple risk factors. Objectives: to determine the frequency of the left ventricle hypertrophy as a marker of cardiovascular da [...] mage and the risk factors leading to its appearance. Methods: a case-control, cross-sectional and prospective study was conducted in 70 patients with renal transplantations and underwent a conventional echocardiogram to determine the presence or not of left ventricle hypertrophy and it was related to cardiovascular risk factors by means of a univariate and multivariate study (logistic regression) with cardiovascular risk factors. Results: the cardiovascular affections were the second cause of loss of patients in present study (33,1%). The left ventricle hypertrophy was found in the 45 (64 %) of screened patients. The dyslipidemia, the use of A cyclosporine and the graft dysfunction, were the complications in the univariate and the multivariate study (independent factor) , p

  7. Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

    Directory of Open Access Journals (Sweden)

    Ulises Novoa

    2010-08-01

    Full Text Available La actividad de Rho kinasa (ROCK cardíaca en la hipertensión arterial (HTA y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionales al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia, o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente, vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC, presión arterial sistólica (PAS y la masa cardíaca relativa (MCR. Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1 como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas, la expresión proteica de colágeno I (por Western blot y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63% (p Background: The effect of cardiac Rho-kinase (ROCK on hypertension (HT and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additional beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks. Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day or the combination of both agents (5 and 25 mg/kg/day, respectively and ROCK inhibitor fasudil (50 mg/kg/day for 3 weeks starting 3 weeks after surgery. Body mass (BM, systolic blood pressure (SBP and relative cardiac mass (RCM were measured. In addition, myosin phosphatase (MYPT-1 phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells, collagen I protein contení (by Western Blot and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63% (p < 0.05, a 300% increase in cardiac MYPT-1 phosphorylation (p< 0.05, 14 times increase in myocardial collagen type 1,270% increase in ED1 cells, a 75% increased gene expression of NADPH oxydase GP91 subunit and a 37% reduction (p< 0.05 in the gene expression of cardiac eNOS. In hypertensive DOCA rats treated during 3 week with candesartan, fasudil or the combination of both, we observed a significant reduction in cardiac hypertrophy and normalization of SBP, MYPT-1 phosphorylation, collagen type I, number of ED1 cells, genic expression of NADPH oxydase GP91 subunit and in the genic expression of cardiac eNOS. Conclusión: The combined use of a ROCK inhibitor and a low dose Angiotensin II receptor blocker was as effective as full doses of both isolated agents in the prevention of cardiac hypertrophy and hypertensive experimental cardiac remodeling (Fondecyt 1085208

  8. Valor clínico de la utilización del strain rate sistólico en el estudio de distintas formas de hipertrofia ventricular izquierda / Clinical Value of Systolic Strain Rate Utilization in the Assessment of Different Types of Left Ventricle Hypertrophy

    Scientific Electronic Library Online (English)

    Sergio, Baratta; Demián, Chejtman; Horacio, Fernández; Fabián E., Ferroni; Jorge, Bilbao; Carol, Kotliar; Norberto, Marani; Domingo, Turri; Alejandro, Hita.

    2007-10-01

    Full Text Available Introducción La hipertrofia del ventrículo izquierdo (HVI) incluye diferentes etiologías, estados evolutivos y pronóstico. El strain rate sistólico (SRS) o estudio de la deformación miocárdica permite analizar la función sistólica regional al evaluar la velocidad de acortamiento miocárdico en funció [...] n del tiempo, con independencia del movimiento traslativo del corazón o del tironeamiento de estructuras vecinas. Objetivo Determinar la utilidad del strain rate sistólico para diferenciar formas de hipertrofia del ventrículo izquierdo. Material y métodos La población del estudio estuvo conformada por cuatro grupos: Grupo 1: (G1, n = 10): voluntarios sanos sedentarios; grupo 2 (G2, n = 21): atletas de alto rendimiento con aumento del índice de masa del ventrículo izquierdo (IMVI) > 125 g/m²; grupo 3 (G3, n = 15): pacientes hipertensos según VII JNC con IMVI > 125 g/m² y grupo 4 (G4, n = 12): pacientes con miocardiopatía hipertrófica (MCH), septum > 15 mm y/o relación septum/pared posterior > 1,5:1, sin causa que lo justifique. Resultados En los grupos con IMVI incrementado no hubo diferencia en la fracción de acortamiento mesoparietal (p = 0,3) o el IMVI (p = 0,6). SRS 01 seg (G1) 0,75 1/s, (G2) 0,87 1/s, (G3) 0,57 1/s, (G4) 0,29 1/s (p Abstract in english Introduction Left ventricular hypertrophy (LVH) includes different etiologies, evolution status and prognosis. Systolic strain rate (SSR) or myocardial deformation assessment allows analyzing the regional systolic function by assessing myocardial shortening velocity throughout time, independently of [...] the translation movement of the heart or pulling of neighboring structures. Objective To determine if the systolic strain rate is a useful resource to differentiate types of left ventricle hypertrophy. Material and methods Study population included four groups: Group 1 (G1, n=10): healthy sedentary volunteers; Group 2 (G2, n=21): highperformance athletes with left ventricle mass index increase (LVMI) >125 g/m²; Group 3 (G3, n=15): hypertensive patients according to VII JNC with LVMI >125 g/m² and Group 4 (G4, n=12): patients with hypertrophic cardiomyopathy (HCM), septum >15 mm and/or posterior septum/wall relation >1,5:1, without any cause. Results There were no differences between groups with increased LVMI in mesoparietal shortening fraction (p=0.3) or LVMI (p=0.6). SRS 01 sec (G1) 0.75 1/s. (G2) 0.87 1/s; (G3) 0.57 1/s; (G4) 0.29 1/s (p

  9. Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-?/PGC-1? signaling mediated energy biosynthesis.

    Science.gov (United States)

    Luan, Aina; Tang, Futian; Yang, Yuhong; Lu, Meili; Wang, Hongxin; Zhang, Yingjie

    2015-05-01

    We previously reported that Astragalus polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced hypertrophy in rats and NRVMs with focus on tumor necrosis factor ? (TNF-?)/peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received isoproterenol injections; (3) Iso+APS, rats received isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated mRNA and protein expression of atrial natriuretic peptide (ANP), increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and protein content, down-regulated mRNA and protein expression of ANP, increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, APS increased the protein expressions of ATP5D, the ? subunit of ATP synthase, PGC-1? and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-? in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-?/PGC-1? signaling mediated energy biosynthesis. PMID:25880160

  10. Beta1-Adrenergic Receptors Promote Focal Adhesion Signaling Downregulation And Myocyte Apoptosis in Acute Volume Overload

    OpenAIRE

    Seqqat, Rachid; Guo, Xinji; Rafiq, Khadija; Kolpakov, Mikhail A.; Guo, Jianfen; Koch, Walter J.; Houser, Steven R.; Dell’italia, Louis J.; Sabri, Abdelkarim

    2012-01-01

    Numerous studies demonstrated increased expression of extracellular matrix (ECM) proteins and activation of focal adhesion (FA) signaling pathways in models of pressure overload-induced cardiac hypertrophy. However, little is known about FA signaling in response to volume overload where cardiac hypertrophy is associated with ECM loss. This study examines the role of beta1-adrenergic receptors (?1-ARs) in FA signaling changes and myocyte apoptosis induced during acute hemodynamic stress of vo...

  11. Trpm4 Gene Invalidation Leads to Cardiac Hypertrophy and Electrophysiological Alterations

    Science.gov (United States)

    Gueffier, Mélanie; Finan, Amanda; Khoueiry, Ziad; Cassan, Cécile; Serafini, Nicolas; Aimond, Franck; Granier, Mathieu; Pasquié, Jean-Luc; Launay, Pierre; Richard, Sylvain

    2014-01-01

    Rationale TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. Objectives We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/-) model. Methods and Results Morpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. Conclusions TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity which impact heart development. PMID:25531103

  12. Origin and mechanisms of heart failure in hypertensive patients: left ventricular remodelling in hypertensive heart disease.

    Science.gov (United States)

    Dubus, I; Samuel, J L; Swynghedauw, B

    1993-11-01

    This review-editorial proposes a biological explanation for most of the physiological characteristics of the hypertrophied chronically overloaded heart. Various growth signals, including mechanical, hormonal and paracrine factors, appear now to be involved in the induction of myocyte hypertrophy and/or phenotypic modifications. A majority of the modifications in passive myocardial compliance are due to an enhanced collagen density, and the diminution of the atrial contribution to ventricular filling is certainly a consequence of an isomyosin change in this particular tissue. The systolic dysfunction reflects, in fact, one of the most essential parts of the adaptational process, the slowing of Vmax. In humans, this diminution is a consequence of a rather complex change in the expression of various genes coding for proteins responsible for myoplasmic calcium transient. Arrhythmogenicity, a well-known detrimental property of the hypertrophied heart, reflects the fragility of calcium homeostasis in this type of cell, and this fragility is likely to be a direct consequence of membrane protein rearrangement. PMID:8281969

  13. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    International Nuclear Information System (INIS)

    Highlights: ? ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ? Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ? Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or ?-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  14. Protein Kinases C and D Mediate Agonist-Dependent Cardiac Hypertrophy through Nuclear Export of Histone Deacetylase 5

    OpenAIRE

    Vega, Rick B.; Harrison, Brooke C; Meadows, Eric; Roberts, Charles R.; Papst, Philip J.; Olson, Eric N; McKinsey, Timothy A

    2004-01-01

    A variety of stress signals stimulate cardiac myocytes to undergo hypertrophy. Persistent cardiac hypertrophy is associated with elevated risk for the development of heart failure. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by triggering phosphorylation- and CRM1-dependent nuclear export of these chromatin-modifying enzymes. However, the identities of cardiac HDAC kinases have remained...

  15. Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.

    Science.gov (United States)

    Narula, J; Arbustini, E; Chandrashekhar, Y; Schwaiger, M

    2001-02-01

    Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure. PMID:11787805

  16. Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas / Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

    Scientific Electronic Library Online (English)

    Ulises, Novoa; María Paz, Ocaranza; Italo, Mora; Jorge, Jalil.

    2010-08-01

    Full Text Available La actividad de Rho kinasa (ROCK) cardíaca en la hipertensión arterial (HTA) y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionale [...] s al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo) unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc) durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día) o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia), o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente), vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC), presión arterial sistólica (PAS) y la masa cardíaca relativa (MCR). Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1) como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas), la expresión proteica de colágeno I (por Western blot) y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63% (p Abstract in english Background: The effect of cardiac Rho-kinase (ROCK) on hypertension (HT) and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additio [...] nal beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks). Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day) or the combination of both agents (5 and 25 mg/kg/day, respectively) and ROCK inhibitor fasudil (50 mg/kg/day) for 3 weeks starting 3 weeks after surgery. Body mass (BM), systolic blood pressure (SBP) and relative cardiac mass (RCM) were measured. In addition, myosin phosphatase (MYPT-1) phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells), collagen I protein contení (by Western Blot) and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63% (p

  17. Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

    DEFF Research Database (Denmark)

    Molina, C.E.; Gesser, Hans

    2007-01-01

    Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current (Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of -87 ± 2 mV and -83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at -120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from -78 ± 3 to -84 ± 3 mV, and stabilized the resting membrane potential at -92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential. teleost heart; IK,ACh; cholinergic modulation; action potential

  18. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca2+]i was measured by flow cytometry using fluo-3. Mitochondrial [Ca2+] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca2+]i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca2+]i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [elevant concentrations increases myocyte [Ca2+]i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

  19. Análise da atividade da enzima conversora da angiotensina na hipertrofia aguda do ventrículo direito em modelo experimental de estenose endovascular ajustável do tronco pulmonar / Evaluation of angiotensin converting enzyme activity in acute right ventricular hypertrophy in an experimental model of adjustable endovascular stenosis of the pulmonary trunk

    Scientific Electronic Library Online (English)

    Renato Rocha, RABELLO; Renato Samy, ASSAD; José Eduardo, KRIEGER; Renata, CARMONA; Maria Cristina, ABDUCH; Sérgio Almeida de, OLIVEIRA.

    2001-12-01

    Full Text Available INTRODUÇÃO: A bandagem do tronco pulmonar (TP) tem sido aplicada para treinamento do ventrículo esquerdo (VE) em pacientes portadores de transposição das grandes artérias (TGA) com septo íntegro. Este procedimento, além de apresentar alta morbi-mortalidade, pode ocasionar alterações da função ventri [...] cular a longo prazo. Com o objetivo de analisar a hipertrofia aguda do ventrículo direito (VD), foi implantado um cateter balão no TP de seis cabritos jovens. MATERIAL E MÉTODOS: A sobrecarga sistólica foi aplicada através de insuflações progressivas do balão, durante 96 horas. Esta hipertrofia foi acompanhada por medidas hemodinâmicas diárias, através de cateteres implantados na aorta, VD e TP, além de ecocardiogramas seriados a cada 24 horas, com medidas das espessuras do septo interventricular e dos ventrículos. Ao final das 96 horas, os animais foram mortos para remoção dos corações. Os ventrículos e o septo foram pesados separadamente. Foram colhidas biópsias musculares de cada câmara para análise da atividade da enzima conversora da angiotensina (ECA). Oito cabritos (idade e peso semelhantes) foram utilizados como controle para os pesos dos ventrículos e para a atividade da ECA. RESULTADOS: Observou-se um aumento do gradiente VD/TP (p=0,001), com conseqüente aumento da razão VD/VE (p=0,005) durante o tempo de sobrecarga sistólica. Ao fim do protocolo, a parede livre do VD apresentou aumento de espessura (p=0,002) e, conseqüentemente, um aumento do peso indexado (p=0,002). A análise da atividade da ECA revelou aumento somente no músculo do VD hipertrofiado (p=0,002). CONCLUSÃO: O cateter balão foi eficiente em induzir a hipertrofia aguda do VD através do protocolo utilizado. Conseqüentemente, um aumento expressivo da atividade da ECA está associado ao processo de hipertrofia miocárdica induzida por sobrecarga pressórica. Abstract in english INTRODUCTION: The pulmonary trunk (PT) banding has been used to promote rapid left ventricular (LV) hypertrophy in patients with transposition of the great vessels (TGV) with intact septum, treated after the neonatal period. This procedure carries a high morbidity and mortality rates. Genetic altera [...] tions of the cardiomyocytes resulting from acute hypertrophy have not been evaluated in models of variable systolic overload of the subpulmonary ventricle. In order to evaluate the activity of angiotensin converting enzyme (ACE) in acute right ventricular (RV) hypertrophy, a balloon catheter was implanted in the PT of six young goats. MATERIAL AND METHODS: Systolic overload was carried out throughout progressive balloon insufflations for a period of 96 hours. Hypertrophy was followed by daily hemodynamic and echocardiographic evaluations. At the end of the 96 hours, the animals were killed to harvest the heart. The ventricles and septum were weighted separately. Samples of each cardiac muscle were collected for ACE analysis. Eight goats (with similar age and weight) were used as control for weight and ACE activity. RESULTS: At the end of the protocol, the following parameters were increased: RV/PT gradient (p=0.001), RV to LV ratio (p=0.005), thickness of the free wall of RV (p=0.002) and RV weight (p=0.002). The evaluation of ACE activity showed an increase only in the hypertrophied RV muscle (p=0.002), indicating a high correlation with the increase in the RV to LV ratio (r=0.87). CONCLUSION: The progressive systolic overload in the RV of goats induces ventricular hypertrophy. This hypertrophy is related to a significant increase in ACE activity, an important molecular marker of this process.

  20. Pharmacological targeting of CDK9 in cardiac hypertrophy.

    Czech Academy of Sciences Publication Activity Database

    Kryštof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, J.

    2010-01-01

    Ro?. 30, ?. 4 (2010), s. 646-666. ISSN 0198-6325 R&D Projects: GA ?R GA204/08/0511; GA ?R GA301/09/1832; GA ?R GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : P-TEFb * cardiac myocyte * cardiac hypertrophy Subject RIV: CE - Biochemistry Impact factor: 10.228, year: 2010

  1. Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: physiologic versus pathologic hypertrophy.

    Science.gov (United States)

    Laks, M M

    1989-12-01

    Ventricular hypertrophy should be divided into at least physiologic and patholgic states in order to clarify structural and functional clinical alterations. The elucidation of the structural, functional, and biochemical mechanisms of ventricular hypertrophy is vital to designing effective preventive and therapeutic measures for the hypertensive patient. Tissue markers may help differentiate pathologic from physiologic hypertrophy. Studies have established the concept that norepinephrine may be a myocardial cellular hypertrophying hormone. The studies ranged from the direct application of norepinephrine to isolated myocardial cells to the chronic subhypertensive infusion of norepinephrine into the conscious, free-roaming dog. Norepinephrine infusion can produce physiologic ventricular hypertrophy or a pathologic state of hypertrophic cardiomyopathy, the former by a three- to four-month infusion and the latter by an infusion of more than six months. The biochemical effect of subhypertensive infusion of norepinephrine was studied prior to the production of ventricular hypertrophy, thereby permitting the elucidation of the mechanism of the hypertrophic process. The biochemical stimulus for the production of myocardial cellular hypertrophy is postulated to be a diminution of cyclic AMP and a stimulation of alpha-1 receptors. Because the ventricular septum has the highest content of adenylate cyclase, which does not increase with cyclic AMP, these changes are postulated to be the biochemical basis for septal hypertrophy in the disease entity hypertrophic cardiomyopathy. A unique conscious-canine model for the production of a myocardial infarction capable of creating a controlled localized occlusion of the coronary artery is presented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2533529

  2. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

    International Nuclear Information System (INIS)

    In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes

  3. Scintigraphic findings in asymmetrical septal hypertrophy with multigated radionuclide angiography

    International Nuclear Information System (INIS)

    Twelve patients with asymmetric septal hypertrophy were studied by mean Multigated Radionuclide Angiography. The ejection fraction, end diastolic volumen, end systolic volumen, and morphological aspects of left ventricle were evaluated. The results were compared with a group of 170 patients (10 normals, 8 aortic valvular stenosis and 152 with coronary artery disease). A significative increase of ejection fraction, a decrease of end systolic volume and abnormal configuration of left ventricular cavity were found in patients with asymmetric septal hypertrophy

  4. Effect of PPAR ? activators on hypertrophic cardiac myocytes in vitro

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of peroxisome proliferator-activated receptor ? (PPAR ?) activators pioglitazone and 15-deoxy-?12,14 prostaglandin J2(15d-PGJ2) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ2, two kinds of PPAR ? activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR ? activators inhibit hypertrophy of cardiac myocytes and PPAR ?-dependent pathway be involved in the inhibitory course

  5. Adenoid hypertrophy presenting with systemic hypertension

    OpenAIRE

    Subashini, P.; Ravikumar, A.; Ranjit, M. S.; Sairam, V. K.; Vatsanath, R. P.; Jayasree, S.

    2007-01-01

    A two and half year old male child was seen with systemic hypertension, left ventricular dysfunction, mitral regurgitation and congestive cardiac failure. Examination revealed adenoid hypertrophy. He was also suffering from obstructive sleep apnea. He was being treated with anti-hypertensive and anti-failure drugs. Adenoidectomy was performed following which obstructive sleep apnea symptoms disappeared and his cardiac status improved markedly. Subsequently he was weaned off anti-hypertensive ...

  6. Adenoid hypertrophy presenting with systemic hypertension.

    Science.gov (United States)

    Subashini, P; Ravikumar, A; Ranjit, M S; Sairam, V K; Vatsanath, R P; Jayasree, S

    2007-03-01

    A two and half year old male child was seen with systemic hypertension, left ventricular dysfunction, mitral regurgitation and congestive cardiac failure. Examination revealed adenoid hypertrophy. He was also suffering from obstructive sleep apnea. He was being treated with anti-hypertensive and anti-failure drugs. Adenoidectomy was performed following which obstructive sleep apnea symptoms disappeared and his cardiac status improved markedly. Subsequently he was weaned off anti-hypertensive and anti-failure therapy. PMID:23120395

  7. Papillary muscle hypertrophy as a structural abnormality in patients with asymmetric septal hypertrophy

    Directory of Open Access Journals (Sweden)

    Mehmet Kanada?ý

    2003-09-01

    Full Text Available Introduction: Asymmetric septal hypertrophy (ASH is the most classical abnormality in hypertrophic cardiomy-opathy (HCM. Segmental hypertrophy of the left ventricle is less frequently observed. Some cases with papillary muscle hypertrophy (PMH particularly associated with apical HCM and also ASH has been reported. Aim of the study: The aim of this study was to determine the frequency of PMH in patients with ASH. Material and methods: Two-dimensional echocardiographic examinations were performed in 42 patients with ASH (group I, 32 patients with left ventricular hypertrophy secondary to hypertension (group II and 26 healthy subjects (group III with comparable mean age and sex. The thickness of the papillary muscles was measu-red either the vertical or horizontal diameter of at least one of the two papillary muscles at end-diastole in short axis view. Papillary muscle hypertrophy was defined, if the papillary muscle diameter was more than the mean + 2 standard deviation of the healthy subjects. Results: The mean thickness of anterior papillary muscle (APM and posterior papillary muscle (PPM were 8.1 ±;1.1 mm and 7.9±;1.0mm, respectively, in group III. Both papillary muscles thickness in-group II and I were greater than group III (p<0.001. Ten (24% and 25 (78% patients had APM hypertrophy in group I and II, respectively. PPM hypertrophy was found in 8 (19% and 21 (66% patients in group I and II, respective-ly. A positive correlation was observed between APM hypertrophy and systolic anterior motion in group I (r= 0.522, p=0.003. There was also a positive correlation between APM hypertrophy and the degree of left ventricularoutflowtract obstruction (r=0.478, p=0.004. Conclusion: Our findings show that PMH is an important component of hypertrophic cardiomyopathy as well as ASH in some patients. Patients with PMH may contribute the occurrence of systolic anterior motion and the degree of left ventricle outflow obstruction.

  8. Revisão dos critérios de Sokolow-Lyon-Rappaport e cornell para hipertrofia do ventrículo esquerdo Revision of the Sokolow-Lyon-Rappaport and cornell voltage criteria for left ventricular hypertrophy

    Directory of Open Access Journals (Sweden)

    Sérgio Lamêgo Rodrigues

    2008-01-01

    Full Text Available FUNDAMENTO: A hipertrofia do ventrículo esquerdo (HVE detectada pela eletrocardiografia é um forte preditor de morbidade e mortalidade cardiovasculares. OBJETIVO: Analisar o desempenho dos critérios de Sokolow-Lyon-Rappaport (SLR e de Cornell, em amostra populacional, em relação ao diagnóstico de HVE à ecocardiografia. MÉTODOS: Entre os 682 participantes da segunda fase do Projeto MONICA-OMS/Vitória, 641 foram avaliados por meio de eletrocardiografia e ecocardiografia. O subgrupo de indivíduos saudáveis (n = 269 foi usado para gerar valores de referência da massa do ventrículo esquerdo (MVE. As sensibilidades e especificidades dos critérios eletrocardiográficos foram determinadas pela curva ROC (receptor-operator characteristics em relação ao diagnóstico de HVE definido pelo critério ecocardiográfico interno (MVE > 48 g/m2,7 e 46 g/m2,7 para homens e mulheres, respectivamente. RESULTADOS: A prevalência de HVE à ecocardiografia foi de 23,7% na amostra global, em que havia 49% de hipertensos. O critério de Cornell apresentou melhor associação com a MVE estimada pela ecocardiografia (r = 0,37; p BACKGROUND: Electrocardiographically-detected left ventricular hypertrophy (LVH is a strong predictor of cardiovascular morbidity and mortality. OBJECTIVE: To assess the performance of the Sokolow-Lyon-Rappaport (SLR and Cornell voltage criteria in a population sample regarding the diagnosis of LVH on echocardiogram (ECHO. METHODS: A total of 641 out of the 682 participants of the second phase of the MONICA-Vitória project were assessed using electrocardiogram and echocardiogram. A subgroup of healthy individuals (n=269 was used to generate reference values of LV mass (LVM. Sensitivities and specificities of the electrocardiographic criteria were determined by the ROC (receptor-operator characteristics curve in relation to the diagnosis of LVH, as defined by the internal echocardiographic criterion (LVM > 48 and 46 g/m2.7 for males and females, respectively. RESULTS: The prevalence of LVH as detected by ECHO was 23.7% in the total sample, in which 49% of the individuals were hypertensive. The Cornell criterion showed a better association with the LVM as estimated by ECHO (r= 0.37, p < 0.01 than the SLR criterion (r= 0.19 as well as a better performance in the analysis of the area under the ROC curve. The new cut-off points for the internally-defined Cornell voltage criterion (2.3 mV for males and 1.9 mV for females showed an acceptable combination of sensitivity (22.5 and 28% for males and females, respectively, with a high specificity (95%. CONLUSION: The classic SLR and Cornell voltage criteria showed a low performance in relation to LVH as detected by the ECHO. However, this accuracy may be improved by using the Cornell voltage criteria defined in the present study.

  9. Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy

    OpenAIRE

    Fisch, Sudeshna; Gray, Susan; Heymans, Stephane; Haldar, Saptarsi M.; Wang, Baiqiu.; Pfister, Otmar; Cui, Lei; Kumar, Ajay; Lin, Zhiyong; Sen-Banerjee, Sucharita; Das, Hiranmoy; Christine A. Petersen; Mende, Ulrike; Burleigh, Barbara A; ZHU Yan

    2007-01-01

    Cardiac hypertrophy is a common response to injury and hemodynamic stress and an important harbinger of heart failure and death. Herein, we identify the Kruppel-like factor 15 (KLF15) as an inhibitor of cardiac hypertrophy. Myocardial expression of KLF15 is reduced in rodent models of hypertrophy and in biopsy samples from patients with pressure-overload induced by chronic valvular aortic stenosis. Overexpression of KLF15 in neonatal rat ventricular cardiomyocytes inhibits cell size, protein ...

  10. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Icli, Basak [Department of Medicine, Cardiovascular Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Bharti, Ajit [Center of Molecular Stress Response Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, MA 02118 (United States); Pentassuglia, Laura; Peng, Xuyang [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States); Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  11. Combinación de un inhibidor de la enzima convertidora de la angiotensina con un antagonista del calcio versus la monoterapia con el IECA: eficacia terapéutica en hipertensión arterial esencial y regresión de la hipertrofia cardíaca / Combination of a Converting Enzyme Inhibitor (ACEI) with a Calcium Antagonist versus Monotherapy with an ACEI: Therapeutic Efficacy in Essential Hypertension and Regression of Ventricular Hypertrophy

    Scientific Electronic Library Online (English)

    Laura M. J., Brandani; Hugo P., Baglivo; Juan J., Rodríguez-Moncalvo; Fernando, Verra; Ramiro A., Sánchez; Agustín J., Ramírez.

    2006-06-01

    Full Text Available Objetivo Evaluar la eficacia y la tolerancia, así como su acción sobre la regresión de la hipertrofia ventricular izquierda, de la combinación de benazepril más amlodipina (B + A) versus la monoterapia con benazepril (B). Material y métodos Se incluyeron 33 hipertensos esenciales. Durante 6 meses de [...] tratamiento, 18 de ellos recibieron B + A (9 varones, 55 ± 2 años) y los 15 restantes recibieron B (10 varones, 49 ± 2 años). Se realizó una presurometría (MAPA) al comienzo y a los 3 y a los 6 meses de tratamiento. En un subgrupo de 23 pacientes se calculó la masa ventricular izquierda (MVI) y el índice de MVI (IMVI) al inicio y al final del tratamiento. Resultados A los 3 meses de tratamiento, los valores de la presión arterial (PA) fueron significativamente menores (p Abstract in english Objective To evaluate the effectiveness, tolerability and effect on the regression of left ventricular hypertrophy, of a combination therapy of amlodipine and benazepril (B+A), versus monotherapy with benazepril (B). Methods We included 33 patients (p) with essential hypertension. During 6 months of [...] treatment, 18 p received B+A (9 men, 55±2 years) and 15 received B (10 men, 49±2 years). An ambulatory blood pressure monitoring (ABPM) was performed at the beginning and at 3 and 6 months of therapy. In a subgroup of 23 patients, left ventricular mass (LVM) and LVM index (LVMI) were calculated from the two dimensional echocardiogram, at the beginning and the end of treatment. Results At 3 months of treatment, blood pressure (BP) values were significantly (p

  12. O eletrocardiograma no diagnóstico da hipertrofia ventricular de pacientes com doença renal crônica El electrocardiograma en el diagnóstico de la hipertrofia ventricular de pacientes con enfermedad renal crónica Electrocardiography in the diagnosis of ventricular hypertrophy in patients with chronic renal disease

    OpenAIRE

    Francisco de Assis Costa; Ivan Romero Rivera; Mirian Lira Castro de Vasconcelos; André Falcão Pedrosa Costa; Rui Manoel dos Santos Póvoa; Maria Tereza Nogueira Bombig; Bráulio Luna Filho; Valter Correia de Lima

    2009-01-01

    FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) é um fator preditor independente de risco cardiovascular e sua caracterização e prevalência na doença renal crônica (DRC) carecem de melhor estudo. OBJETIVO: Estabelecer o diagnóstico de HVE em pacientes com DRC em estágio 5 por seis diferentes critérios eletrocardiográficos, correlacionando-os com o índice de massa do ventrículo esquerdo (IMVE) obtido pelo ecocardiograma. MÉTODOS: Estudo transversal que incluiu 100 pacientes (...

  13. Parasistolia ventricular / Ventricular parasistolia

    Scientific Electronic Library Online (English)

    Antonio, Cortés-Ortiz.

    2014-03-01

    Full Text Available Se presenta el caso de un hombre de 54 años de edad con historia de un infarto del miocardio inferior antiguo y función ventricular izquierda normal, cuya atención en la consulta externa de nuestra institución se inició por palpitaciones frecuentes. El electrocardiograma mostró extrasístoles ventric [...] ulares de una morfología y en el monitoreo Holter se documentó extrasístoles ventriculares frecuentes de una morfología con periodos de acoplamiento variable y con latidos de fusión. Se concluyó la presencia de un foco parasistólico ventricular. Abstract in english We present a case of a 54 years old male who had had an inferior myocardial infarction previously, with normal ejection fraction of the left ventricle whose care in the autopatient clinic of our institution started by frequent palpitations. The electrocardiogram showed premature ventricular contract [...] ions and Holter monitoring documented frequent premature ventricular contractions with periods of variable coupling and fusion beats. It was concluded the presence of ventricular parasystole.

  14. Buckwheat Rutin Inhibits AngII-induced Cardiomyocyte Hypertrophy via Blockade of CaN-dependent Signal Pathway

    OpenAIRE

    Chu, Jin-xiu; Li, Guang-Min; Gao, Xiu-juan; Wang, Jian-xing; Han, Shu-Ying

    2014-01-01

    Buckwheat rutin has been found to be able to inhibit angiotensin II (AngII) - induced hypertrophy in cultured neonatal rat cardiomyocytes, but the mechanism remains uncertain. In this study, myocardial hypertrophy model was made by adding AngII to the medium of cardiac myocytes of neonatal rats; meanwhile, different concentrations of buckwheat rutin were applied to observe their effects. Intracellular Ca2+ level was detected by Hitachi - 850 fluorospectrophotometer, calcineurin (CaN) activity...

  15. Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

    OpenAIRE

    Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F; Sadoshima, Junichi; Tian, Bin

    2011-01-01

    Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pa...

  16. Coupling an HCN2-expressing cell to a myocyte creates a two-cell pacing unit

    Science.gov (United States)

    Valiunas, V; Kanaporis, G; Valiuniene, L; Gordon, C; Wang, H Z; Li, L; Robinson, R B; Rosen, M R; Cohen, I S; Brink, P R

    2009-01-01

    We examined whether coupling of a ventricular myocyte to a non-myocyte cell expressing HCN2 could create a two-cell syncytium capable of generating sustained pacing. Three non-myocyte cell types were transfected with the mHCN2 gene and used as sources of mHCN2-induced currents. They were human mesenchymal stem cells and HEK293 cells, both of which express connexin43 (Cx43), and HeLa cells transfected with Cx43. Cell–cell coupling between heterologous pairs increased with time in co-culture, and hyperpolarization of the myocyte induced HCN2 currents, indicating current transfer from the mHCN2-expressing cell to the myocyte via gap junctions. The magnitude of the HCN2 currents recorded in myocytes increased with increasing junctional conductance. Once a critical level of electrical cell–cell coupling between myocytes and mHCN2 transfected cells was exceeded spontaneous action potentials were generated at frequencies of ?0.6 to 1.7 Hz (1.09 ± 0.05 Hz). Addition of carbenoxolone (200 ?m), a gap junction channel blocker, to the media stopped spontaneous activity in heterologous cell pairs. Carbenoxolone washout restored activity. Blockade of HCN2 currents by 100 ?m 9-amino-1,2,3,4-tetrahydroacridine (THA) stopped spontaneous activity and subsequent washout restored it. Neither THA nor carbenoxolone affected electrically stimulated action potentials in isolated single myocytes. In summary, the inward current evoked in the genetically engineered (HCN2-expressing) cell was delivered to the cardiac myocyte via gap junctions and generated action potentials such that the cell pair could function as a pacemaker unit. This finding lays the groundwork for understanding cell-based biological pacemakers in vivo once an understanding of delivery and target cell geometry is defined. PMID:19736302

  17. Nitric oxide inhibits endothelin-1-induced neonatal cardiomyocyte hypertrophy via a RhoA-ROCK-dependent pathway.

    Science.gov (United States)

    Hunter, J Craig; Zeidan, Asad; Javadov, Sabzali; Kili?, Ana; Rajapurohitam, Venkatesh; Karmazyn, Morris

    2009-12-01

    Although nitric oxide (NO) has received extensive attention as an anti-hypertrophic agent the mechanisms underlying its regulation of endothelin-1 (ET-1) have not been fully elucidated. Since RhoA has been identified as an important mediator of cardiac hypertrophy and is inhibited by NO in vascular tissue, we sought to determine whether the anti-ET-1 effects of NO in cardiomyocytes were mediated via inhibition of the RhoA-ROCK cascade in the context of cardiac hypertrophy. Neonatal rat ventricular myocytes were cultured in the presence of ET-1 (10 nM) with or without pre-treatment with the NO donor S-nitroso-n-acetylpenicillamine (SNAP; 100 microM), 8-Br-cGMP (cGMP; 100 microM), the RhoA inhibitor C3 exoenzyme (C3; 30 ng/ml), or the ROCK inhibitor Y-27632 (10 microM). ET-1-induced cardiomyocyte hypertrophy was prevented by pre-treatment with SNAP, cGMP, C3, or Y-27632. The hypertrophic response to ET-1 was associated with significantly increased gene and protein expression of both NOS2 and NOS1 although NOS3 was unaffected. ET-1 treatment for 15 min increased membrane-bound RhoA 2.6-fold (p<0.05), which was prevented by both SNAP and cGMP (p<0.05). These effects were associated with a complete abrogation of ET-1-induced phosphorylation of the downstream target of RhoA, cofilin-2, that was mimicked by direct inhibition of RhoA and ROCK. In addition, confocal microscopy and Western blotting revealed that 24 h ET-1 treatment reduced the G- to F-actin ratio 67% (p<0.05) which was prevented by SNAP, cGMP, C3 and Y (p<0.05). Taken together, these results suggest that the anti-hypertrophic effects of NO are due, in part, to cGMP-dependent inhibition of the RhoA-ROCK-cofilin signalling pathway. These findings may be important in understanding the mechanisms of anti-ET-1 and anti-hypertrophic effects of NO as well as in the development of novel RhoA-targeted therapeutic interventions for treating cardiac hypertrophy. PMID:19799911

  18. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoulas Takis

    2007-03-01

    Full Text Available Abstract Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II, but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest; and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient, but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM.

  19. Heart-Healthy Hypertrophy

    OpenAIRE

    Trivedi, Chinmay M.; Epstein, Jonathan A.

    2011-01-01

    Exercise induces growth of heart muscle cells and heart size. A new report in Cell (Boström et al., 2010) suggests that mice also respond to exercise with increased cardiac myocyte proliferation, and the molecular regulators of this pathway are linked to maladaptive and pathologic responses to cardiac stresses such as pressure overload.

  20. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Dimaano, Veronica L

    2013-01-01

    The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.

  1. A mathematical model of the mechanical link between shortening of the cardiomyocytes and systolic deformation of the left ventricular myocardium

    DEFF Research Database (Denmark)

    Smerup, Morten Holdgaard; Partridge, J

    2013-01-01

    Left ventricular myocytes are arranged in a complex three-dimensional mesh. Since all myocytes contract approximately to the same degree, mechanisms must exist to enable force transfer from each of these onto the framework as a whole, despite the transmural differences in deformation strain. This process has hitherto not been clarified in detail.

  2. Fatty acid utilization in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H2O left atrial filling pressure with a ventricular afterload of 80 cm of H2O with buffer containing 1.2 mM 14C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14CO2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14CO2 production during this time was 0.728 +/- 0.06 ?moles/min/g dry in control hearts and 0.710 +/- 0.02 ?moles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 ?moles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

  3. Ventricular arrhythmias.

    OpenAIRE

    Kavanagh, K. M.; Wyse, D. G.

    1988-01-01

    Sudden cardiac death claims thousands of Canadians annually. Ventricular tachycardia and fibrillation account for up to 85% of these deaths. Identifying the patients at risk remains a major challenge. Those who have recurrent ventricular tachycardia or have been resuscitated from ventricular fibrillation are generally considered to be at highest risk. Although ventricular premature beats in the absence of previous ventricular tachycardia or fibrillation are not helpful in identifying such pat...

  4. Taking the first steps in contraction mechanics of single myocytes from frog heart.

    Science.gov (United States)

    Brandt, P W; Colomo, F; Poggesi, C; Tesi, C

    1993-01-01

    Intact or skinned atrial and ventricular myocytes from frog heart were mounted horizontally between the lever arms of a force transducer and a servo-controlled electromagnetic loud-speaker "motor" in a trough filled with Ringer or relaxing solution. The myocyte length-sarcomere length relation for intact preparations at rest is linear at least in the range from l0 (sarcomere length about 2.1 microns, resting force zero) to 1.6 l0 (resting force about 100 nN). The peak force value for control twitches (21-23 degrees C, stimulus interval 10 s, [Ca2+]o 1 mM) varies from 20 to 100 nN in atrial and ventricular intact myocytes. The effects induced by isoprenaline or changes in [Ca2+]o, stimulation pattern and bath temperature on twitch characteristics are comparable to those observed in multicellular preparations. The steady force produced by maximally Ca(2+)-activated skinned myocytes is much greater than that developed in control twitches and varies from 0.5 to 3.5 microN in different cells. The saturating pCa in the activating solution is around 5.50. The force response of a resting myocyte to slow ramp stretches shows an initial velocity- and length-dependent component during the stretch itself and, after completion of the length change, a gradual recovery towards a steady level which only depends on the stretch extent. The force response of a stimulated myocyte to length steps complete in 2 ms consists of an apparently elastic change during the step itself and then of a rapid partial recovery followed by slowering of recovery. Whether or not the force recovery includes different phases as reported for skeletal muscle remains unclear. PMID:8109374

  5. Adiponectin ameliorates hyperglycemia-induced cardiac hypertrophy and dysfunction by concomitantly activating Nrf2 and Brg1.

    Science.gov (United States)

    Li, Haobo; Yao, Weifeng; Irwin, Michael G; Wang, Tingting; Wang, Shuang; Zhang, Liangqing; Xia, Zhengyuan

    2015-07-01

    Hyperglycemia-induced oxidative stress is implicated in the development of cardiomyopathy in diabetes that is associated with reduced adiponectin (APN) and heme oxygenase-1 (HO-1). Brahma-related gene 1 (Brg1) assists nuclear factor-erythroid-2-related factor-2 (Nrf2) to activate HO-1 to increase myocardial antioxidant capacity in response to oxidative stress. We hypothesized that reduced adiponectin (APN) impairs HO-1 induction which contributes to the development of diabetic cardiomyopathy, and that supplementation of APN may ameliorate diabetic cardiomyopathy by activating HO-1 through Nrf2 and Brg1 in diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were untreated or treated with APN adenovirus (1×10(9) pfu) 3 weeks after diabetes induction and examined and terminated 1 week afterward. Rat left ventricular functions were assessed by a pressure-volume conductance system, before the rat hearts were removed to perform histological and biochemical assays. Four weeks after diabetes induction, D rats developed cardiac hypertrophy evidenced as increased ratio of heart weight to body weight, elevated myocardial collagen I content, and larger cardiomyocyte cross-sectional area (all PH9C2 cells incubated with high glucose (HG, 25 mM), supplementation of recombined globular APN (gAd, 2?g/mL) reversed HG-induced reductions of HO-1, Brg1, and nuclear Nrf2 protein expression and attenuated cellular oxidative stress, myocyte size, and apoptotic cells. Inhibition of HO-1 by ZnPP (10?M) or small interfering RNA (siRNA) canceled all the above gAd beneficial effects. Moreover, inhibition of Nrf2 (either by the Nrf2 inhibitor luteolin or siRNA) or Brg1 (by siRNA) canceled gAd-induced HO-1 induction and cellular protection in CMs and in H9C2 cells incubated with HG. In summary, our present study demonstrated that APN reduced cardiac oxidative stress, ameliorated cardiomyocyte hypertrophy, and prevented left ventricular dysfunction in diabetes by concomitantly activating Nrf2 and Brg1 to facilitate HO-1 induction. PMID:25795513

  6. Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy.

    OpenAIRE

    Jaffre?, Fabrice; Bonnin, Philippe; Callebert, Jacques; Debbabi, Haythem; Setola, Vincent; Doly, Ste?phane; Monassier, Laurent; Mettauer, Bertrand; Blaxall, Burns; Launay, Jean-marie; Maroteaux, Luc

    2009-01-01

    By mimicking sympathetic stimulation in vivo, we previously reported that mice globally lacking serotonin 5-HT(2B) receptors did not develop isoproterenol-induced left ventricular hypertrophy. However, the exact cardiac cell type(s) expressing 5-HT(2B) receptors (cardiomyocytes versus noncardiomyocytes) involved in pathological heart hypertrophy was never addressed in vivo. We report here that mice expressing the 5-HT(2B) receptor solely in cardiomyocytes, like global 5-HT(2B) receptor-null m...

  7. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling

    OpenAIRE

    Paradis, Pierre; Dali-Youcef, Nassim; Paradis, François W; Thibault, Gaétan; Nemer, Mona

    2000-01-01

    Angiotensin II (AII) is a major determinant of arterial pressure and volume homeostasis, mainly because of its vascular action via the AII type 1 receptor (AT1R). AII has also been implicated in the development of cardiac hypertrophy because angiotensin I-converting enzyme inhibitors and AT1R antagonists prevent or regress ventricular hypertrophy in animal models and in human. However, because these treatments impede the action of AII at cardiac as well as vascular levels, and reduce blood pr...

  8. Left ventricular mass in male adolescent athletes and non-athletes

    Directory of Open Access Journals (Sweden)

    Erling David Kaunang

    2014-09-01

    Full Text Available Background Systematic exercise leads to increased left ventricular mass, which may be misleading in a differential diagnosis of heart disease in athletes (physiologic hypertrophy versus pathologic hypertrophy. The cause of left ventricular hypertrophy is an important risk factor in the morbidity and mortality of cardiovascular diseases. Objective To compare left ventricular mass and left ventricular hypertrophy in male adolescent athletes and non-athletes. Methods We conducted a cross-sectional, analytic study, from September to December 2012 in male adolescents aged 15-18 years. The case group included athletes from the Bina Taruna Football Club Manado, while the control group included non-athlete adolescents. All subjects underwent history-taking, physical examinations and further supporting examinations. Left ventricular mass was measured by cardiovascular echocardio-graphy (Esaote Mylab 4.0 and calculated based on a formula. Left ventricular hypertrophy was defined as left ventricular mass of > 134 g/m2 body surface area. Results Subjects’ mean left ventricular masses were 359.69 (SD 188.4; 95%CI 283.58 to 435.81 grams in the athlete group and 173.04 (SD 50.69; 95%CI 152.56 to 103.51 grams in the non-athlete group, a statistically significant difference (P=0.0001. Ventricular hypertrophy was found 76.9% compared to 11.5% in the non-athlete group (P=0.0001. Conclusion Left ventricular mass in athletes is bigger than in non-athletes. In addition, left ventricular hypertrophy is more common in male adolescent athletes than in non-athletes. [Paediatr Indones. 2014;54:305-8.].

  9. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism.

    OpenAIRE

    Sadoshima, J; Izumo, S

    1993-01-01

    It is well known that external load plays a critical role in determining cardiac muscle mass and its phenotype, but little is known as to how mechanical load is transduced into intracellular signals regulating gene expression. To address this question we analyzed the 'mechano-transcription' coupling process using an in vitro model of load-induced cardiac hypertrophy, in which a stretch of rat cardiac myocytes, grown on a deformable substrate, causes a rapid induction of immediate-early genes ...

  10. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strom, C.C.; Kruhoffer, M.

    2004-01-01

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat.

  11. Identification of a Core Set of Genes That Signifies Pathways Underlying Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Søren P. Sheikh

    2006-04-01

    Full Text Available Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46 of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat

  12. A study on premature ventricular contractions caused by ultrasound exposure with microbubbles using cultured ventricular muscle cells

    International Nuclear Information System (INIS)

    It has been shown that diagnostic ultrasound examination using a contrast agent can cause premature ventricular contractions (PVCs). In this study, we investigated a usefulness of a new technique using cultured cardiac myocytes to study mechanisms of PVC production. Cardiac myocytes were isolated from neonatal rats and cultured on a cover glass. The cover glass was attached to an observation chamber in which it was possible to observe changes in myocytes during ultrasound exposure. In the experiments, cardiac myocytes were exposed to pulsed ultrasound in the presence and absence of microbubbles. The pressure amplitudes (peak-negative pressures) were set at 5 steps, -0.28, -0.55, -0.73, -0.92 and -1.1 MPa, and threshold pressure to produce a PVC was recorded. The results showed that the presence of microbubbles attached to a cell reduces threshold pressure for producing PVCs, and it was concluded that our method is useful for studying the mechanisms of PVC production

  13. H11 has dose-dependent and dual hypertrophic and proapoptotic functions in cardiac myocytes

    Science.gov (United States)

    Hase, Makoto; Depre, Christophe; Vatner, Stephen F.; Sadoshima, Junichi

    2005-01-01

    We have shown previously that H11, a serine/threonine kinase, is up-regulated in a heart subjected to ischaemia/reperfusion. In the present study, we have characterized the cellular function of H11, using neonatal rat cardiac myocytes. Although transduction of adenovirus harbouring H11 at low doses increased the cell size, at higher doses it induced apoptosis in cardiac myocytes. Apoptosis was not observed when adenovirus harbouring H11-KI (kinase-inactive mutant of H11) was used, suggesting that the proapoptotic effect of H11 is kinase-dependent. The hypertrophic effect of H11 at high doses was unmasked when apoptosis was inhibited by the caspase inhibitor DEVD-CHO, suggesting that H11 stimulates both hypertrophy and apoptosis in parallel. H11-KI induced hypertrophy even at high doses, indicating that H11 stimulates hypertrophy through kinase-independent mechanisms. H11-KI activated Akt, and cardiac hypertrophy induced by H11-KI was blocked by LY294002, an inhibitor of phosphoinositide 3-kinase. Co-immunoprecipitation analyses indicated that H11 interacts with the ? subunit of CK2 (casein kinase 2). Overexpression of H11 decreased the kinase activity of CK2. DRB (5,6-dichloro-1-?-D-ribofuranosyl-benzimidazole), an inhibitor of CK2, mimicked the effect of H11, whereas DRB and H11 failed to exhibit additive effects on apoptosis, suggesting that H11 and DRB utilize a common mechanism to induce apoptosis, namely inhibition of CK2. In summary, H11 is a dual-function kinase in cardiac cells: it induces hypertrophy at low doses through kinase-independent activation of Akt, whereas it causes apoptosis at high doses through protein kinase-dependent mechanisms, in particular by physical interaction with and subsequent inhibition of CK2. PMID:15656793

  14. Haematopoietic and right ventricular response to intermittent hypobaric hypoxia in meat-type chickens.

    Science.gov (United States)

    Julian, R J; Squires, E J

    1994-09-01

    The purpose of this study was to examine the effect of simulated high altitude (2054 m) on erythropoiesis and pulmonary hypertension-induced right ventricular hypertrophy. Broiler chickens were reared at atmospheric pressure (altitude 295 m) or in a hypobaric chamber at an atmospheric pressure of 592 mmHg (calculated partial pressure of oxygen: 124 mmHg; calculated altitude and O2 equivalents: 2054 m and 16.3%) for 2-, 4-, 8- or 16-h periods out of each 24 h. Hypoxia of 2 and 4 h per day had little effect on blood parameters although there was some indication of right ventricular hypertrophy. Hypoxia of 8 or 16 h produced significantly higher haematocrit and haemoglobin levels than controls, and there was moderate to marked right ventricular hypertrophy. The relationship between right ventricular hypertrophy and duration of hypoxia was greater than between polycythaemia and duration of hypoxia. PMID:18671120

  15. Left ventricular mass in borderline hypertension assessed by echo cardiography

    International Nuclear Information System (INIS)

    The relationship between clinical measurement of blood pressure (BP) and left ventricular hypertrophy in arterial hypertension appears to be weak in most studies. On the contrary, stronger correlations with target organ damage in general, and left ventricular hypertrophy in particular, have been reported for blood pressure measurements obtained by ambulatory monitoring; this finding may indicate a possible role for blood pressure response to naturally occurring stresses in determining left ventricular hypertrophy. Aim of this study was to investigate, in 18 patients with borderline arterial hypertension, the relationships between echocardiographically assessed left ventricular mass and, respectively, casual BP and BP responses to some standardized stress tests. Only three patients had a diastolic wall thickness of the interventricular septum and of the posterior wall ?1.2 cm and none had a pathologically increased left ventricular mass index. The following statistically significant correlations were found: casual diastolic BP vs. left ventricular mass index (r=0.53, p<0.02), systolic BP response to bicycle exercise test vs. left ventricular mass index (r=0.55, p<0.05). Multiple regression analysis showed that almost fifty percent of the variability of left ventricular mass index could be predicted by these two BP measurements. These findings suggest that besides the chronically increased afterload, also the transient hypertensive responses to naturally occuring physive responses to naturally occuring physical stresses may have a role in determining the extent of cardiac structural changes in borderline hypertensive patients. In addition, they indicate a direct relation between left ventricular mass and blood pressure levels also in borderline hypertension, as previously shown for established hypertension, despite the fact that left ventricular hypertrophy represents only an occasional finding in early stages of hypertension

  16. Calmodulin Mediates Differential Sensitivity of CaMKII and Calcineurin to Local Ca2+ in Cardiac Myocytes

    OpenAIRE

    Saucerman, Jeffrey J; Bers, Donald M

    2008-01-01

    Calmodulin (CaM) mediates Ca-dependent regulation of numerous pathways in the heart, including CaM-dependent kinase (CaMKII) and calcineurin (CaN), yet the local Ca2+ signals responsible for their selective activation are unclear. To assess when and where CaM, CaMKII, and CaN may be activated in the cardiac myocyte, we integrated new mechanistic computational models of CaM, CaMKII, and CaN with the Shannon-Bers model of excitation-contraction coupling in the rabbit ventricular myocyte. These ...

  17. The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy

    OpenAIRE

    Sadoshima, Junichi; Montagne, Olivier; Wang, Qian; Yang, Guiping; Warden, Jill; Liu, Jing; Takagi, Gen; Karoor, Vijaya; Hong, Chull; JOHNSON, GARY L.; Vatner, Dorothy E.; Vatner, Stephen F

    2002-01-01

    Mitogen-activated protein kinase kinase kinase (MEKK1) mediates activation of c-Jun NH2-terminal kinase (JNK). Although previous studies using cultured cardiac myocytes have suggested that the MEKK1-JNK pathway plays a key role in hypertrophy and apoptosis, its effects in cardiac hypertrophy and apoptosis are not fully understood in adult animals in vivo. We examined the role of the MEKK1-JNK pathway in pressure-overloaded hearts by using mice deficient in MEKK1. We found that transverse aort...

  18. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2) inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética / Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Scientific Electronic Library Online (English)

    Cristian, Aguilar; Freddy, Ventura; Luis, Rodríguez-Delfín.

    2011-06-01

    Full Text Available Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos [...] en tres grupos: (1) ratas control, (2) ratas diabéticas y (3) ratas diabéticas tratadas con atorvastatina (50 mg/kg/día). Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético. Abstract in english Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divide [...] d into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  19. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2 inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2 mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2011-06-01

    Full Text Available Objetivos. Evaluar el efecto de atorvastatina sobre la progresión del remodelado cardiaco y la expresión de ECA-2 en el miocardio de ratas diabéticas. Materiales y métodos. La diabetes fue inducida en ratas Holtzman con una inyección intraperitoneal de estreptozotocina. Los animales fueron divididos en tres grupos: (1 ratas control, (2 ratas diabéticas y (3 ratas diabéticas tratadas con atorvastatina (50 mg/kg/día. Después de ocho semanas de tratamiento, los corazones fueron extraídos para el análisis morfométrico, la cuantificación de colágeno y la determinación de los niveles de ARNm de ECA y ECA-2. Resultados. El índice de hipertrofia ventricular y el depósito de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de atorvastatina previno estos cambios sin modificar los niveles de colesterol. La hiperglicemia produjo un incremento significativo en los niveles del ARNm de ECA y una marcada disminución en la expresión de ECA-2 en el miocardio de ratas diabéticas. La administración de atorvastatina indujo la expresión del ARNm de ECA-2 e inhibió la sobreexpresión del ARNm de ECA en el miocardio de las ratas diabéticas. Conclusiones. Nuestros resultados indican que la atorvastatina, independientemente de su capacidad para disminuir el colesterol, normaliza la relación de la expresión de ECA/ECA-2 y atenúa el desarrollo del remodelado adverso en el corazón diabético.Objectives. This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats. Materials and Methods. Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1 normal control rats, (2 diabetic rats and (3 diabetic rats treated orally with atorvastatin (50 mg/kg/day. After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  20. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function.

    Czech Academy of Sciences Publication Activity Database

    McDermott-Roe, Ch.; Ye, J.; Ahmed, R.; Sun, X. M.; Serafín, A.; Ware, J.; Bottolo, L.; Muckett, P.; Ca?as, X.; Zhang, J.; Rowe, G. C.; Buchan, R.; Lu, H.; Braithwaite, A.; Mancini, M.; Hauton, D.; Martí, R.; García-Arumí, E.; Hubner, N.; Jacob, H.; Serikawa, T.; Zídek, Václav; Papoušek, František; Kolá?, František; Cardona, M.; Ruiz-Meana, M.; García-Dorado, D.; Comella, J. X.; Felkin, L. E.; Barton, P. J. R.; Arany, Z.; Pravenec, Michal; Petretto, E.; Sanchis, D.; Cook, S.A.

    2011-01-01

    Ro?. 478, ?. 7367 (2011), s. 114-118. ISSN 0028-0836 R&D Projects: GA MŠk(CZ) 1M0520; GA ?R(CZ) GA301/08/0166 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular hypertrophy * endonuclease G * mitochondrial dysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 36.280, year: 2011

  1. Hypertrophic cardiomyopathy without hypertrophy: two families with myocardial disarray in the absence of increased myocardial mass.

    OpenAIRE

    McKenna, W J; Stewart, J. T.; Nihoyannopoulos, P.; McGinty, F; Davies, M J

    1990-01-01

    Two families are described in which individuals showed widespread myocardial disarray at histological examination, in the absence of macroscopic cardiac hypertrophy. In one family the clinical presentation was that of sudden unexpected cardiac death in four family members; members of the other family presented with electrocardiographic repolarisation changes and abnormalities of left ventricular diastolic function. The finding of myocardial disarray, the characteristic histological abnormalit...

  2. Congenital Generalised Hypertrophy of Feet

    OpenAIRE

    Agarwal AK; Srivastava PK; Kumar D

    2009-01-01

    Local hypertrophy, gigantism or overgrowth of hand, foot,part of it (Macrodactyly) or of full extremity are commonlyseen in Klippel Trenaunay Parkes Weber Syndrome.However congenital generalized hypertrophy of feet is arare presentation and a search of the literature revealedone case report in a 25 year old female, a similar case isbeing presented here.

  3. Estereologia do miocárdio de ratos jovens e idosos Stereology of the myocytes in young and aged rats

    Directory of Open Access Journals (Sweden)

    Márcia Barbosa Águila

    1998-02-01

    Full Text Available OBJETIVO: Comparar as diferenças quantitativas na composição e estrutura do miocárdio de ratos jovens e idosos utilizando a estereologia. MÉTODOS: Foram estudados 30 ratos machos da raça Wistar (15 animais jovens de 3 meses de idade e 15 animais idosos de 15 meses. Os corações foram retirados, pesados, perfundidos com solução de Bouin e posteriormente fixados em formol tamponado a 10% por 24h, processados por técnica histológica, incluídos em parafina, seccionados e corados pelo HE e picro-sirius. Foram analisados 15 campos aleatórios por grupo e foram determinados os seguintes parâmetros estereológicos: densidade de volume do miócito (Vv[miócito] e densidade de volume do interstício cardíaco (Vv[interstício] e densidade numérica dos miócitos (Nv[miócito] (1/mm³, estimados pelo método disector. O número total de miócitos (N[miócitos] e a média do volume do miócito (Vol[miócito] dos corações dos dois grupos também foram determinados. As diferenças estatísticas entre os animais jovens e idosos foram testadas pelo teste não paramétrico de Mann-Whitney. RESULTADOS: Comparando os animais dos grupos jovem e idoso temos, respectivamente, os seguintes dados: o peso cardíaco aumentou de 1,1 para 1,7g, o Vv(miócito diminuiu de 76,7 para 72,2%, Vv(interstício aumentou de 23,3 para 27,8%, enquanto o Nv(miócito diminuiu de 14,76x10(4 para 6,19x10(4/mm³. O Vol(miócito aumentou de 5,42x10³ para 13,26x10³mm³ e o N(miócito diminuiu de 15,64x10(4 para 10,72x10(4 miócitos. Estas diferenças foram estatisticamente significativas (pPURPOSE: To determine the myocardial quantitative changes comparing young and aged animals by using the stereology. METHODS: Thirty rat hearts were studied (15 rats aged 3 months and 15 other rats aging 15 months. The hearts were removed, weighed, fixed in 10% buffered formaldehyde solution, embedded in paraffin, cut in 7µm thick slices and stained with HE and picro-sirius stains. In each group we counted 15 random microscopic fields. The following parameters were studied: Vv(myocyte and Vv(interstitium(% (the volume densities of the cardiac myocyte and interstitium, determined by the point-counting method, and Nv(myocyte (1/mm³ (the numerical density of the cardiac myocytes, determined with the disector method. The total number of myocytes (N[myocyte] and the mean volume of the myocytes (V[myocytes] were also determined. The differences were tested by the Mann-Whitney test.RESULTS: Cardiac weight increased from 1.1 to 1.7g, the Vv(myocyte decreased from 76.7 to 72.2%, the Vv(interstitium increased from 23.3 to 27.8%. The Nv(myocyte and the N(myocyte decreased from 14.76x10(4 to 6.19x10(4/mm³ and 15.64x10(4 to 10.72x10(4 myocytes, respectively. Simultaneously, the V(myocyte increased from 5.42x10³ to 13.26x10³mm³. These differences were statistically significant (p<0.05. CONCLUSION: Myocardial changes, comparing young rats with aged ones suggest loss of myocytes (increased apoptosis? with simultaneous myocyte hypertrophy.

  4. Endothelial and non-endothelial coronary blood flow reserve and left ventricular dysfunction in systemic hypertension

    OpenAIRE

    Aloísio Marchi Rocha; Vera Maria Cury Salemi; Pedro Alves Lemos Neto; Afonso Yoshikiro Matsumoto; Valéria Fontenelle Angelim Pereira; Fábio Fernandes; Luciano Nastari; Charles Mady

    2009-01-01

    OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arter...

  5. Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats

    Scientific Electronic Library Online (English)

    M.A., Carneiro-Júnior; M.C.G., Pelúzio; C.H.O., Silva; P.R.S., Amorim; K.A., Silva; M.O., Souza; C.A., Castro; D., Roman-Campos; T.N., Prímola-Gomes; A.J., Natali.

    1042-10-01

    Full Text Available We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), t [...] readmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myocytes were isolated enzymatically, and resting cell length, width, and cell shortening after stimulation at a frequency of 1 Hz (~25°C) were measured. Cell length was greater in TRA than in SED-8 (161.30 ± 1.01 vs 156.10 ± 1.02 ?m, P

  6. Rate-dependency of action potential duration and refractoriness in isolated myocytes from the rabbit AV node and atrium

    OpenAIRE

    Workman, A. J.; Kane, K. A.; Rankin, A. C.

    2000-01-01

    During atrial fibrillation, ventricular rate is determined by atrioventricular nodal (AVN) conduction, which in part is dependent upon the refractoriness of single AVN cells. The aims of this study were to investigate the rate-dependency of the action potential duration (APD) and effective refractory period (ERP) in single myocytes isolated from the AV node and atrium of rabbit hearts, using whole cell patch clamping, and to determine the contribution of the 4-aminopyridine (4-AP)-sensitive c...

  7. Exercise training and detraining modify the morphological and mechanical properties of single cardiac myocytes obtained from spontaneously hypertensive rats

    OpenAIRE

    Carneiro-ju?nior, M. A.; Pelu?zio, M. C. G.; Silva, C. H. O.; Amorim, P. R. S.; Silva, K. A.; Souza, M. O.; Castro, C. A.; Roman-campos, D.; Pri?mola-gomes, T. N.; Natali, A. J.

    2010-01-01

    We determined the effects of exercise training and detraining on the morphological and mechanical properties of left ventricular myocytes in 4-month-old spontaneously hypertensive rats (SHR) randomly divided into the following groups: sedentary for 8 weeks (SED-8), sedentary for 12 weeks (SED-12), treadmill-running trained for 8 weeks (TRA, 16 m/min, 60 min/day, 5 days/week), and treadmill-running trained for 8 weeks followed by 4 weeks of detraining (DET). At sacrifice, left ventricular myoc...

  8. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in keeping with its failure to translocate to the nucleus, the beta-arrestin2-scaffolded pool of ERK1/2 does not phosphorylate the transcription factor Elk-1, induces no increased transcription of the immediate-early gene c-Fos, and does not entail myocyte hypertrophy. These results clearly demonstrate the biological significance of differential signalling by the AT(1)R. The opportunity to separate desirable cardiac myocyte division from detrimental hypertrophy holds promise that novel pharmacological approaches will allow targeting of pathway-specific actions.

  9. Influence of fatty acid oxidation rate on glycerol release from cardiac myocytes

    International Nuclear Information System (INIS)

    Quiescent cardiac myocytes are characterized by low rates of fatty acid oxidation due to the reduced energy demand compared with beating hearts. The accumulation of intracellular fatty acid metabolites may, therefore, result in feed-back inhibition of the cardiac lipase responsible for the mobilization of triacylglycerols (lipolysis). The objective of this study was to examine if interventions that increase fatty acid oxidation rates in myocytes have an effect on lipolysis. Addition of 100 ?M dinitrophenol (DNP) to calcium-tolerant rat ventricular myocytes caused an increase in the rate of 14C-oleic acid oxidation from 1.11 +/- 0.06 to 2.38 +/- 0.17 nmol 14CO2/106 cells/min (115% stimulation; mean +/- S.D., n = 3). In parallel incubations, DNP increased the rate of lipolysis from 4.4 +/- 1.7 to 13.6 +/- 3.2 nmol glycerol/106 cells/30 min (215% stimulation). The addition of 1 mM barium to a modified Ringer's incubation medium produced an increase in the contractile activity of the myocytes, and increased the rates of oleic acid oxidation from 0.62 +/- 0.16 to 0.88 +/- 0.23 nmol/106 cells/min (42% stimulation; n = 6) and lipolysis from 13.1 +/- 6.5 to 22.2 +/- 6.4 nmol/106 cells/30 min (70% stimulation). These data show that stimulation of fatty acid oxidation in myocardial myocytes is accompanied by increased lipolytic rates, the latter probably due to release of feed-back inhibition of cardiac lipases by accumulated fatty acid metabolites

  10. Quantitative thallium-201 myocardial imaging in assessing right ventricular pressure in patients with congenital heart defects

    International Nuclear Information System (INIS)

    Thallium-201 myocardial scintigraphy was performed in patients with congenital heart defects to determine whether, by quantification of right ventricular isotope uptake, one could assess the degree of right ventricular hypertrophy and so predict the level of right ventricular pressure. It is shown that quantitative analysis of myocardial imaging with thallium-201 is of use clinically in patients with congenital heart defects, in assessing the severity of pulmonary stenosis or the presence of pulmonary artery hypertension. (author)

  11. Inhibitory Effects of Methylsulfonylmethane on Ventricular Hypertrophy Related Gene Expression

    OpenAIRE

    Sara Mostafalou; Masoud Darabi; Shabnam Fayezi; Yadollah Omidi; Nasrin Maleki-Dizaji; Hossein Hamzeiy; Moslem Najafi; Alireza Garjani; Sadollah Mohammadi; Kambiz Hassanzadeh; Sajjad Khani

    2012-01-01

    Methylsulfonylmethane (MSM) is naturally accruing organic sulphur that is known as a potent anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on mRNA expressions of angiotensinogen, endothelin-1 (ET-1) and Transforming Growth Factor (TGF)-?1 in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension. Wistar rats were randomly assigned to 38-days pretreatment or 28-days treatment. MSM was administered to either 10 days before or 14 days after...

  12. Inhibitory Effects of Methylsulfonylmethane on Ventricular Hypertrophy Related Gene Expression

    Directory of Open Access Journals (Sweden)

    Sara Mostafalou

    2012-01-01

    Full Text Available Methylsulfonylmethane (MSM is naturally accruing organic sulphur that is known as a potent anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on mRNA expressions of angiotensinogen, endothelin-1 (ET-1 and Transforming Growth Factor (TGF-?1 in rats with monocrotaline (MCT-induced pulmonary arterial hypertension. Wistar rats were randomly assigned to 38-days pretreatment or 28-days treatment. MSM was administered to either 10 days before or 14 days after a single dose of MCT. Right Ventricle (RV tissue samples were obtained to evaluate changes in the inflammatory genes expression using RT-PCR assay. The expression levels of angiotensinogen, ET-1 and TGF-?1 significantly were reduced (p<0.01 at efficient dose of MSM in MCT-induced pulmonary arterial hypertensive rats. Results suggest that harmful effects of MCT induced PAH on the RV function could be attenuated by anti-inflammatory actions through the suppression of local RAAS along with associated growth-promoting factors TGF-?1 and ET-1.

  13. Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy

    OpenAIRE

    Gupta, Sudhiranjan; Maitra, Ratan; Young, Dave; Gupta, Anasuya; Sen, Subha

    2009-01-01

    Myotrophin-induced activation of NF-?B has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-?B activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among seve...

  14. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

    Scientific Electronic Library Online (English)

    T., Fernandes; U.P.R., Soci; E.M., Oliveira.

    2011-09-01

    Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological card [...] iac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, ?-myosin heavy chain and ?-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  15. Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

    Directory of Open Access Journals (Sweden)

    Martins A.S.

    2001-01-01

    Full Text Available Ascending aorta coarctation was produced by a minimally invasive technique in rabbits. Animal mortality was 5%. Morphometric and hemodynamic parameters were evaluated. A parabiotically isolated heart model was used to assess the hemodynamic parameters. Left ventricular weight/body weight ratio and muscle area showed clear evidence of hypertrophy when compared to control. The hemodynamic changes in the isolated heart model suggested decreased diastolic and systolic function in the coarcted group. The present model produced hypertrophy with low mortality rates as a result of its less invasive nature.

  16. Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

    Scientific Electronic Library Online (English)

    A.S., Martins; N.W., Aguilera; B.B., Matsubara; E.A., Bregagnollo.

    2001-03-01

    Full Text Available Ascending aorta coarctation was produced by a minimally invasive technique in rabbits. Animal mortality was 5%. Morphometric and hemodynamic parameters were evaluated. A parabiotically isolated heart model was used to assess the hemodynamic parameters. Left ventricular weight/body weight ratio and m [...] uscle area showed clear evidence of hypertrophy when compared to control. The hemodynamic changes in the isolated heart model suggested decreased diastolic and systolic function in the coarcted group. The present model produced hypertrophy with low mortality rates as a result of its less invasive nature.

  17. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  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.

    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 occurred were assessed in 863 hypertensive patients with electrocardiographic left ventricular hypertrophy aged 55 to 80 years (mean: 66 years) during 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Echocardiography substudy. Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height(2.7) >or=46.7 g/m(2.7) and 49.2 g/m(2.7) in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity, isolated systolic hypertension, and mitral regurgitation (all P<0.01). Ejection fraction, stress-corrected midwall shortening, and prevalence of left ventricular hypertrophy were higher in women at baseline and at the end of study (all P<0.01). In particular, more women had residual eccentric hypertrophy (47% versus 32%; P<0.01) in spite of similar in-treatment reduction in mean blood pressure. In logistic regression, left ventricular hypertrophy at study end was more common in women (odds ratio: 1.61; 95% CI: 1.16 to 2.26; P<0.01) independent of other significant covariates. In linear regression analyses, female gender also predicted 2% higher mean in-treatment ejection fraction and 2% higher mean stress-corrected midwall shortening (both beta=0.07; P<0.01). Hypertensive women in this study retained higher left ventricular ejection fraction and stress-corrected midwall shortening in spite of less hypertrophy regression during long-term antihypertensive treatment Udgivelsesdato: 2008/4

  19. Patterns of left ventricular remodeling among patients with essential and secondary hypertension / Patrones de remodelación ventricular en pacientes con hipertensión arterial primaria y secundaria

    Scientific Electronic Library Online (English)

    Dan, Radulescu; Laurentiu, Stoicescu; Elena, Buzdugan; Valer, Donca.

    2013-12-01

    Full Text Available Antecedentes: La hipertensión arterial causa hipertrofia ventricular izquierda, un factor de mal pronóstico en pacientes hipertensos. Objetivo: Evaluar patrones de remodelación ventricular en pacientes con hipertensión arterial esencial y secundaria a daño renal. Material y Métodos: Análisis de ecoc [...] ardiogramas efectuados a 250 pacientes con hipertensión arterial primaria (150 mujeres) y 100 pacientes con hipertensión secundaria (60 mujeres). Se midió el grosor del septum interventricular y de la pared ventricular posterior. La masa ventricular izquierda se calculó usando la fórmula de Devereaux. Resultados: Los tipos más frecuentes de remodelación ventricular en mujeres y hombres con hipertensión esencial fueron la hipertrofia ventricular excéntrica y concéntrica, respectivamente. En pacientes con hipertensión arterial secundaria, la hipertrofia concéntrica fue más frecuente. La prevalencia de hipertrofia ventricular izquierda fue más alta en pacientes con hipertensión secundaria. El índice de masa ventricular izquierda y el grosor relativo de la pared ventricular izquierda fueron mayores en pacientes con hipertensión secundaria. La edad, los valores de presión arterial y la duración de la hipertensión influyeron en los patrones de remodelación. Conclusiones: Documentamos una mayor prevalencia de hipertrofia ventricular izquierda en pacientes con hipertensión secundaria. El tipo de remodelación depende de la edad, género, tipo de hipertensión, valores de presión arterial y duración de la hipertensión Abstract in english Background: High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. Aim: To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. M [...] aterial and Methods: We analyzed data from echocardiograms performed in 250patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interventricular septum and the left ventricular posterior wall thickness were measured in the parasternal long-axis. Left ventricular mass was calculated using the Devereaux formula. Results: The most common remodeling type in females and males with essential hypertension were eccentric and concentric left ventricular hypertrophy (cLVH), respectively. Among patients with secondary arterial hypertension, cLVH was most commonly observed in both genders. The prevalence of left ventricular hypertrophy was higher among patients with secondary hypertension. The left ventricular mass index and the relative left ventricular wall thickness were higher in males and also in the secondary hypertension group. Age, blood pressure values and the duration of hypertension, influenced remodeling patterns. Conclusions: We documented a higher prevalence of LVH among patients with secondary hypertension. The type of ventricular remodeling depends on gender, age, type of hypertension, blood pressure values and the duration of hypertension.

  20. Increased clearance of reactive aldehydes and damaged proteins in hypertension-induced compensated cardiac hypertrophy : impact of exercise training

    DEFF Research Database (Denmark)

    Campos, Juliane Cruz; Fernandes, Tiago

    2015-01-01

    Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. Conclusion. Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.

  1. Comparative study of Scrophulariae and Aconite in inhibiting myocardial hypertrophy in rats and mice

    Directory of Open Access Journals (Sweden)

    Wei-liang GU

    2008-04-01

    Full Text Available Objective: To explore the effects of Scrophulariae of cold nature and Aconite of hot nature on myocardial hypertrophy and neuroendocrine factors in rats and mice.Methods: A mouse model of myocardial hypertrophy was established by hypodermic injection of isoproterenol. Sixty myocardial hypertrophy mice were randomly divided into five groups: normal control group, untreated group, metoprolol-treated group, Scrophulariae-treated group and Aconite-treated group. A rat model of myocardial hypertrophy was established by peritoneal injection of L-thyroxin. Fifty rats were randomly divided into five groups: normal control group, untreated group, captopril-treated group, Scrophulariae-treated group and Aconite-treated group. After 7-9 days of treatment with intragastric administration of the corresponding drugs, the effects of Scrophulariae and Aconite on left ventricular weight index (LVWI and heart weight index (HWI were determined. The concentrations of cyclic adenosine monophosphate (cAMP in plasma and angiotensin? (Ang? in myocardium were detected through radio-immunity method. Cardiocyte cross-section area was determined by using HE staining. Results: Scrophulariae of cold nature could significantly reduce the LVWI, HWI and cardiocyte cross-section area, and could decrease the content of cAMP and Ang?. However, Aconite had no such effects. Conclusion: Scrophulariae of cold nature can inhibit myocardial hypertrophy through restraining the activity of sympathetic nervous system and decreasing the level of Ang?. The inhibition of Aconite of hot nature on cardiac hypertrophy is not significant.

  2. Myocytes Oxygenation and High Energy Phosphate Levels during Hypoxia

    OpenAIRE

    Jameel, Mohammad Nurulqadr; Hu, Qingsong; Zhang, Jianyi

    2014-01-01

    Decrease of ambient oxygen level has been used in myocytes culture experiments in examining the responsiveness to stress secondary to hypoxia. However, none of these studies measure the myocytes oxygenation levels resulting in ambiguity as to whether there is insufficient oxygen delivery. This study examined the hypothesis that at a basal myocardial work state, adequate myocyte oxygenation would be maintained until extremely low arterial pO2 levels were reached. Myocyte pO2 values in normal d...

  3. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate.

    Science.gov (United States)

    Piao, Lin; Sidhu, Vaninder K; Fang, Yong-Hu; Ryan, John J; Parikh, Kishan S; Hong, Zhigang; Toth, Peter T; Morrow, Erik; Kutty, Shelby; Lopaschuk, Gary D; Archer, Stephen L

    2013-03-01

    Pyruvate dehydrogenase kinase (PDK) is activated in right ventricular hypertrophy (RVH), causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. The stimulus for PDK upregulation, its isoform specificity, and the long-term effects of PDK inhibition are unknown. We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate. Adult male Fawn-Hooded rats (FHR) with pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH; age 6-12 months) were compared to age-matched controls. Glucose oxidation (GO) and fatty acid oxidation (FAO) were measured at baseline and after acute dichloroacetate (1 mM × 40 min) in isolated working hearts and in freshly dispersed RV myocytes. The effects of chronic dichloroacetate (0.75 g/L drinking water for 6 months) on cardiac output (CO) and exercise capacity were measured in vivo. Expression of PDK4 and its regulatory transcription factor, FOXO1, were also measured in FHR and RV specimens from PAH patients (n = 10). Microarray analysis of 168 genes related to glucose or FA metabolism showed >4-fold upregulation of PDK4, aldolase B, and acyl-coenzyme A oxidase. FOXO1 was increased in FHR RV, whereas HIF-1 ? was unaltered. PDK4 expression was increased, and the inactivated form of FOXO1 decreased in human PAH RV (P < 0.01). Pyruvate dehydrogenase (PDH) inhibition in RVH increased proton production and reduced GO's contribution to the tricarboxylic acid (TCA) cycle. Acutely, dichloroacetate reduced RV proton production and increased GO's contribution (relative to FAO) to the TCA cycle and ATP production in FHR (P < 0.01). Chronically dichloroacetate decreased PDK4 and FOXO1, thereby activating PDH and increasing GO in FHR. These metabolic changes increased CO (84 ± 14 vs. 69 ± 14 ml/min, P < 0.05) and treadmill-walking distance (239 ± 20 vs. 171 ± 22 m, P < 0.05). Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores GO, leading to improved bioenergetics and RV function in RVH. PMID:23247844

  4. Effects of rosiglitazone on fibroblast conditioned growth medium-induced myocardial hypertrophy and its mechanism in rats

    Directory of Open Access Journals (Sweden)

    Xiao-xing ZHU

    2011-07-01

    Full Text Available Objective To investigate the inhibitory effect of rosiglitazone(RSG on fibroblast conditioned growth medium(FCGM-induced myocardial hypertrophy and its mechanism in rats.Methods FCGM-stimulated protein synthesis and protein kinase C(PKC activity were measured in neonatal rat ventricular cardiomyocytes in the absence or presence of RSG or the PKC inhibitor chelerythrine(che.Results Cultured neonatal rat ventricular fibroblast conditioned growth medium significantly enhanced protein synthesis of cardiomyocytes.Meanwhile ET-1 was detected in FCGM using the enzyme-linked immunosorbent assay(ELISA.RSG and che counteracted the growth promoting effect of FCGM possibly via suppressing PKC activity.Conclusion FCGM-induced myocardial hypertrophy may be associated with ET-1.The inhibitory effects of RSG on myocardial hypertrophy may be mediated through ET-1 and PKC.

  5. Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules.

    Science.gov (United States)

    Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F; Sadoshima, Junichi; Tian, Bin

    2011-01-01

    Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the "fetal gene program". Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3'UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842

  6. Mitochondria in cardiac hypertrophy and heart failure

    OpenAIRE

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2012-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenerget...

  7. Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P

  8. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  9. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    International Nuclear Information System (INIS)

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed IK1 channels is low enough. At too high an expression level of IK1 channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of IK1 channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of IK1 channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expto allow to observe oscillations. With expression levels below ?1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of IK1 has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations

  10. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

    Science.gov (United States)

    Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

    2015-01-01

    Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

  11. Cytosolic CARP Promotes Angiotensin II- or Pressure Overload-Induced Cardiomyocyte Hypertrophy through Calcineurin Accumulation

    OpenAIRE

    Chen, CI; Shen, Liang; Cao, Shiping; Li, Xixian; Xuan, Wanling; Zhang, JingWen; Huang, Xiaobo; Bin, Jianping; Xu, Dingli; Li, Guofeng; Kitakaze, Masafumi; Liao, Yulin

    2014-01-01

    The gene ankyrin repeat domain 1 (Ankrd1) is an enigmatic gene and may exert pleiotropic function dependent on its expression level, subcellular localization and even types of pathological stress, but it remains unclear how these factors influence the fate of cardiomyocytes. Here we attempted to investigate the role of CARP on cardiomyocyte hypertrophy. In neonatal rat ventricular cardiomyocytes (NRVCs), angiotensin II (Ang II) increased the expression of both calpain 1 and CARP, and also ind...

  12. Asymmetric septal hypertrophy of sporadic form with abnormal thallium perfusion and myocardial enzymes

    International Nuclear Information System (INIS)

    Asymmetric septal hypertrophy with abnormal thallium scintigram and elevated cardiac enzymes were observed in five patients and were studied with special reference to the clinical significance of their clinicopathological features. They were not familial cardiomyopathy patients. Two of the five patients (Cases 1 and 2) exhibited the clinical features characteristic of hypertrophic cardiomyopathy without abnormal thallium perfusion and serum cardiac enzyme levels. A right endomyocardial biopsy for Case 1 disclosed myocardial fibrosis in addition to hypertrophy and disarray of myocardial fibers. The left ventricular cavities of two other patients (Cases 4 and 5) tended to be dilated with signs of impaired systolic function and asymmetric septal hypertrophy. A regional area of reduced thickness was observed in the medial portion of the left ventricular posterior wall of Case 4. The remaining case (Case 3) exhibited left ventricular dilatation and reduced left ventricular systolic function, disproportionate hypertrophy, and had clinical signs of congestive heart failure. Necropsy disclosed massive fibrosis and diffuse disarray of myocardial fibers. Some patients with familial hypertrophic cardiomyopathy progress to exhibit clinical features of dilated cardiomyopathy in the termimal stages, and have massive fibrosis of the myocardium histologically. Thallium scintigraphic abnormalities and elevated serum levels of cardiac enzymes, especially the LDH1 isoenzyme, especially the LDH1 isoenzyme, in patients with hypertrophic cardiomyopathy may be a meaningful indicator of such progression in its early stages. The five patients in the present study exhibited a variety of clinical and histological features which may comprise a spectrum of clinical conditions during the progression from hypertrophic cardiomyopathy to a condition like dilated cardiomyopathy, similar to that in familial patients. This progression and the factors promoting it should be studied further in the near future. (author)

  13. Fibroblast Growth Factor 2 Mediates Isoproterenol-induced Cardiac Hypertrophy through Activation of the Extracellular Regulated Kinase

    Directory of Open Access Journals (Sweden)

    Stacey L. House

    2010-01-01

    Full Text Available Fibroblast growth factor 2 (basic FGF or FGF2 has been shown to affect growth and differentiation in some tissues and to be required for cardiac hypertrophy in vivo. FGF2 has been shown in vitro to signal through the mitogen-activated protein kinase (MAPK to affect cell survival and growth. To ascertain the role of FGF2 in cardiac hypertrophy, wildtype, Fgf2 knockout, non-transgenic, and FGF2 transgenic mice were treated with isoproterenol or saline via subcutaneous mini-osmotic pump implants to induce a hypertrophic response to b-adrenergic stimulation. Fgf2 knockout hearts are protected from isoproterenol-induced cardiac hypertrophy; whereas, FGF2 transgenic hearts show exacerbated cardiac hypertrophy as assessed by heart weight-to-body weight ratios and myocyte cross-sectional area. Echocardiography reveals significantly decreased fractional shortening in isoproterenol-treated FGF2 transgenic mice but not in Fgf2 knockout mice suggesting that FGF2 mediates the maladaptive cardiac dysfunction seen in cardiac hypertrophy induced by isoproterenol. Western blot analysis also reveals alterations in MAPK signaling in Fgf2 knockout and FGF2 transgenic hearts subjected to isoproterenol treatment, suggesting that this cascade mediates FGF2's pro-hypertrophic effect.

  14. EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes, by Activating AMPK-Dependent Pathway

    Science.gov (United States)

    Zhao, Li; Qin, Yuan

    2015-01-01

    AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy. PMID:25954124

  15. Calcium binding to cardiac myocytes protected from proteolytic enzyme activity.

    Science.gov (United States)

    Bailey, L E; Fawzi, A B

    1985-04-17

    Excitation-contraction coupling in cardiac muscle is dependent on extracellular calcium and calcium bound to the surface of the myocardial cell. In this study, we examined the physical characteristics of calcium binding to adult guinea pig ventricular myocytes disaggregated mechanically in oxygenated tissue culture medium containing a proteinase inhibitor (aprotinin), and separated from cellular debris by Cytodex beads. Cells prepared in this manner excluded Trypan blue and showed no evidence of spontaneous contraction or contracture. Scatchard plots of calcium binding determined by continuous flow equilibrium dialysis revealed a high-affinity, low-capacity pool, Ka = 65 X 10(3) M-1 and Bt = 1.3 nmol X mg-1 and a low-affinity, high-capacity pool, Ka = 141 M-1 and Bt = 138 nmol X mg-1. The low-affinity pool was not detectable after lanthanum, trypsin or collagenase treatment or in cells prepared without aprotinin in the isolation medium. Both neuraminidase and phospholipase C reduced Bt of the low-affinity pool by one half, but only neuraminidase affected the affinity constant of this pool. Ka was increased to 516.7 M-1, similar to the apparent affinity constant for calcium binding estimated from dP/dtmax measured at several extracellular calcium concentrations (470 M-1). The results suggest that calcium bound to sarcolemmal phospholipids represents the superficial calcium involved in excitation-contraction coupling in the heart. PMID:3986217

  16. Myocyte renewal and therapeutic myocardial regeneration using various progenitor cells.

    Science.gov (United States)

    Hayashi, Emiko; Hosoda, Toru

    2014-11-01

    Whereas the demand on effective treatment options for chronic heart failure is dramatically increasing, the recent recognition of physiological and pathological myocyte turnover in the adult human heart provided a fundamental basis for the therapeutic regeneration. Divergent modalities were experimentally introduced to this field, and selected ones have been applied clinically; the history began with skeletal myoblasts and bone-marrow-derived cells, and lately mesenchymal stem/stromal cells and resident cardiac cells joined the repertoire. Among them, autologous transplantation of c-kit-positive cardiac stem cells in patients with chronic ventricular dysfunction resulted in an outstanding outcome with long-lasting effects without increasing major adverse events. To further optimize currently available approaches, we have to consider multiple factors, such as the targeting disease, the cell population and number to be administered, and the timing and the route of cell delivery. Exploration of the consequence of the previous clinical trials would allow us to envision an ideal cellular therapy for various cardiovascular disorders. PMID:24743881

  17. Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy A redução da pressão de perfusão coronariana está associada com a fibrose endocárdica no modelo de hipertrofia por sobrecarga de volume em ratos

    Directory of Open Access Journals (Sweden)

    Maria Carolina Guido

    2004-01-01

    Full Text Available Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each and their respective controls (sham-operated controls - Sh, Sh4 and Sh8 (8 rats each. Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg, used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1 than in Sh8 (100.8 ± 1.3, but comparable between aortocaval fistula 4 (50.0 ± 8.9 and Sh4 (84.8 ± 2.3. Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P No remodelamento que se segue às sobrecargas de volume não é descrito o aumento de fibrose miocárdica. Após o infarto, entretanto, há hipertrofia do miocárdio remoto com acúmulo de fibrose, particularmente no subendocárdio. Na fístula aorto-cava, tal como no infarto, é possível que a queda da pressão de perfusão coronariana interfira com a fibrose cardíaca. OBJETIVO: Investigar o papel das mudanças hemodinâmicas agudas sobre a fibrose cardíaca na fístula aorto-cava. MÉTODO: Ratos Wistar submetidos a fístula aorto-cava, seguidos por 4 e 8 semanas, constituíram 4 grupos, fístula aorto-cava 4 e fístula aorto-cava 8 (10 ratos cada e seus respectivos controles (sham-operated controls - Sh, Sh4 e Sh8 (8 ratos cada. A hemodinâmica foi realizada 1 semana após a cirurgia. A hipertrofia e a fibrose foram quantificadas ao final do seguimento pelo diâmetro dos miócitos e pela fração de volume do colágeno. RESULTADOS: Comparados com Sh4 e Sh8, a pressão de pulso, a pressão diastólica final do ventrículo esquerdo e a +dP/dt foram maiores em fístula aorto-cava 4 e fístula aorto-cava 8, enquanto a -dP/dt foi similar. A pressão estimada da perfusão coronariana (mmHg foi menor em fístula aorto-cava 8 (52,6±4,1 do que em Sh8 (100,8±1,3, mas comparável entre fístula aorto-cava 4 (50,0±8,9 e Sh4 (84,8±2,3. O diâmetro dos miócitos foi maior em fístula aorto-cava 8 e a fibrose intersticial e subendocárdica maior em fístula aorto-cava 4 e fístula aorto-cava 8. Houve correlação inversa e independente da pressão de perfusão coronariana com a fibrose subendocárdica (r²=0,86; p<0,0001 e das pressões sistólica (r²=0,73; p=0,0035 e diastólica final do ventrículo esquerdo (r²=0,55; p=0.0124 com a fibrose intersticial. CONCLUSÃO: A queda precoce da pressão de perfusão coronariana e o aumento das pressões ventriculares após a fístula aorto-cava associam-se com fibrose miocárdica subseqüente.

  18. Hypertrophic cardiomyopathy with apical left ventricular aneurysm.

    Science.gov (United States)

    Akutsu, Y; Shinozuka, A; Huang, T Y; Watanabe, T; Yamada, T; Yamanaka, H; Saitou, T; Geshi, E; Takenaka, H; Takeyama, Y; Munechika, H; Ban, Y; Katagiri, T

    1998-02-01

    We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level. PMID:9559432

  19. Arrhythmogenic Right Ventricular Dysplasia

    Science.gov (United States)

    MENU Return to Web version Arrhythmogenic Right Ventricular Dysplasia Overview What is arrhythmogenic right ventricular dysplasia? Arrhythmogenic right ventricular dysplasia (say: “uh-rith-mo-jen-ic right ven-trick- ...

  20. Microtubules mobility affects the modulation of L-type ICa by muscarinic and beta-adrenergic agonists in guinea-pig cardiac myocytes

    OpenAIRE

    Gallo, Maria Pia; Alloatti, Giuseppe; Levi, Renzo

    2003-01-01

    To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. We observed that the stabilization of microtubules with paclitaxel (1 microM for 1-4 h) did not markedly affect either the kinetics of I(Ca), or the stimulatory effect of isoprot...

  1. Masseter muscle hypertrophy: case report

    Scientific Electronic Library Online (English)

    Eduardo Kazuo, Sannomya; Marcelo, Gonçalves; Marcelo Paraíso, Cavalcanti.

    Full Text Available A hipertrofia dos músculos masseteres caracteriza-se aumento uni ou bilateral dos músculos masseteres, atingindo igualmente homens e mulheres depois da puberdade. Sua etiologia é desconhecida. Os sintomas incluem limitação da abertura bucal e tensão na região dos músculos hipertrofiados. Este artigo [...] apresenta um caso de hipertrofia de músculo masseter, com várias modalidades imagens, tais como radiografia convencional, tomografia computadorizada e ressonância magnética. É muito importante um conhecimento profundo desta condição para estabelecer o diagnostico diferencial de outras patologias, como tumores da glândula parótida e infecção dental. Abstract in english Masseter muscle hypertrophy is characterized by unilateral or bilateral enlargement of the masseter muscles affecting both males and females after puberty. Its etiology remains unknown. Limitations on mouth opening and also tension in the region of the hypertrophied muscle are symptoms reported. Thi [...] s paper reports a case of masseter muscle hypertrophy diagnosed using imaging modalities such as conventional radiography, computed tomography and magnetic resonance imaging scans. The familiarity with this condition is important to settle the differential diagnosis with other pathologies such as parotid gland tumors and dental infection.

  2. Functional consequences of caspase activation in cardiac myocytes

    Science.gov (United States)

    Communal, Catherine; Sumandea, Marius; de Tombe, Pieter; Narula, Jagat; Solaro, R. John; Hajjar, Roger J.

    2002-01-01

    Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including ?-actin, ?-actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of ?-actin and ?-actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using ?-adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity. Induction of apoptosis in cardiac cells was associated with similar cleavage of myofilaments. Therefore, activation of apoptotic pathways may lead to contractile dysfunction before cell death. PMID:11972044

  3. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. PMID:25863256

  4. A mechanistic role for cardiac myocyte apoptosis in heart failure

    OpenAIRE

    Wencker, Detlef; Chandra, Madhulika; NGUYEN, Khanh; Miao, Wenfeng; Garantziotis, Stavros; FACTOR, STEPHEN M.; Shirani, Jamshid; Armstrong, Robert C.; Kitsis, Richard N.

    2003-01-01

    Heart failure is a common, lethal condition whose pathogenesis is poorly understood. Recent studies have identified low levels of myocyte apoptosis (80–250 myocytes per 105 nuclei) in failing human hearts. It remains unclear, however, whether this cell death is a coincidental finding, a protective process, or a causal component in pathogenesis. Using transgenic mice that express a conditionally active caspase exclusively in the myocardium, we demonstrate that very low levels of myocyte apop...

  5. Allopurinol Benefits Left Ventricular Mass and Endothelial Dysfunction in Chronic Kidney Disease

    OpenAIRE

    Kao, Michelle P.; Ang, Donald S.; Gandy, Stephen J.; Nadir, M. Adnan; Houston, J. Graeme; Lang, Chim C.; Struthers, Allan D.

    2011-01-01

    Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD a...

  6. Current concepts on ventricular fibrillation: a vicious circle of cardiomyocyte calcium overload in the initiation, maintenance, and termination of ventricular fibrillation.

    Science.gov (United States)

    Zaugg, Christian E

    2004-01-01

    Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF) are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds) increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning) due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction. PMID:16943975

  7. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Christian E. Zaugg

    2004-04-01

    Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

  8. Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation

    Science.gov (United States)

    Li, Ning; Timofeyev, Valeriy; Tuteja, Dipika; Xu, Danyan; Lu, Ling; Zhang, Qian; Zhang, Zhao; Singapuri, Anil; Albert, Trevine R; Rajagopal, Amutha V; Bond, Chris T; Periasamy, Muthu; Adelman, John; Chiamvimonvat, Nipavan

    2009-01-01

    Small conductance Ca2+-activated K+ channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Morover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild-type animals. No ventricular arrhythmias are detected in the null mutant mice or wild-type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias. PMID:19139040

  9. Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

    Science.gov (United States)

    Koivumäki, Jussi T; Korhonen, Topi; Takalo, Jouni; Weckström, Matti; Tavi, Pasi

    2009-01-01

    Background The cardiomyocyte is a prime example of inherently complex biological system with inter- and cross-connected feedback loops in signalling, forming the basic properties of intracellular homeostasis. Functional properties of cells and tissues have been studied e.g. with powerful tools of genetic engineering, combined with extensive experimentation. While this approach provides accurate information about the physiology at the endpoint, complementary methods, such as mathematical modelling, can provide more detailed information about the processes that have lead to the endpoint phenotype. Results In order to gain novel mechanistic information of the excitation-contraction coupling in normal myocytes and to analyze sophisticated genetically engineered heart models, we have built a mathematical model of a mouse ventricular myocyte. In addition to the fundamental components of membrane excitation, calcium signalling and contraction, our integrated model includes the calcium-calmodulin-dependent enzyme cascade and the regulation it imposes on the proteins involved in excitation-contraction coupling. With the model, we investigate the effects of three genetic modifications that interfere with calcium signalling: 1) ablation of phospholamban, 2) disruption of the regulation of L-type calcium channels by calcium-calmodulin-dependent kinase II (CaMK) and 3) overexpression of CaMK. We show that the key features of the experimental phenotypes involve physiological compensatory and autoregulatory mechanisms that bring the system to a state closer to the original wild-type phenotype in all transgenic models. A drastic phenotype was found when the genetic modification disrupts the regulatory signalling system itself, i.e. the CaMK overexpression model. Conclusion The novel features of the presented cardiomyocyte model enable accurate description of excitation-contraction coupling. The model is thus an applicable tool for further studies of both normal and defective cellular physiology. We propose that integrative modelling as in the present work is a valuable complement to experiments in understanding the causality within complex biological systems such as cardiac myocytes. PMID:19715618

  10. Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

    Directory of Open Access Journals (Sweden)

    Weckström Matti

    2009-08-01

    Full Text Available Abstract Background The cardiomyocyte is a prime example of inherently complex biological system with inter- and cross-connected feedback loops in signalling, forming the basic properties of intracellular homeostasis. Functional properties of cells and tissues have been studied e.g. with powerful tools of genetic engineering, combined with extensive experimentation. While this approach provides accurate information about the physiology at the endpoint, complementary methods, such as mathematical modelling, can provide more detailed information about the processes that have lead to the endpoint phenotype. Results In order to gain novel mechanistic information of the excitation-contraction coupling in normal myocytes and to analyze sophisticated genetically engineered heart models, we have built a mathematical model of a mouse ventricular myocyte. In addition to the fundamental components of membrane excitation, calcium signalling and contraction, our integrated model includes the calcium-calmodulin-dependent enzyme cascade and the regulation it imposes on the proteins involved in excitation-contraction coupling. With the model, we investigate the effects of three genetic modifications that interfere with calcium signalling: 1 ablation of phospholamban, 2 disruption of the regulation of L-type calcium channels by calcium-calmodulin-dependent kinase II (CaMK and 3 overexpression of CaMK. We show that the key features of the experimental phenotypes involve physiological compensatory and autoregulatory mechanisms that bring the system to a state closer to the original wild-type phenotype in all transgenic models. A drastic phenotype was found when the genetic modification disrupts the regulatory signalling system itself, i.e. the CaMK overexpression model. Conclusion The novel features of the presented cardiomyocyte model enable accurate description of excitation-contraction coupling. The model is thus an applicable tool for further studies of both normal and defective cellular physiology. We propose that integrative modelling as in the present work is a valuable complement to experiments in understanding the causality within complex biological systems such as cardiac myocytes.

  11. PGC-1? accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    International Nuclear Information System (INIS)

    Energy metabolism and Ca2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1?) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1? in cardiac Ca2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1? via adenoviral transduction. Our data shows that overexpressing PGC-1? improved myocyte contractility without increasing the amplitude of Ca2+ transients, suggesting that myofilament sensitivity to Ca2+ increased. Interestingly, the decay kinetics of global Ca2+ transients and Ca2+ waves accelerated in PGC-1?-expressing cells, but the decay rate of caffeine-elicited Ca2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), but not Na+/Ca2+ exchange (NCX) contribute to PGC-1?-induced cytosolic Ca2+ clearance. Furthermore, PGC-1? induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1? did not disturb cardiac Ca2+ homeostasis, because SR Ca2+ load and the propensity for Ca2+ waves remained unchanged. These data suggest that PGC-1? can ameliorate cardiac Ca2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1?-calcium handing pathway sheds new light on the role of PGC-1? in the therapy of cardiac diseases.

  12. MuRF1 Negatively Regulates Pathological Cardiac Hypertrophy Through Downregulation of Calcineurin A

    Science.gov (United States)

    Maejima, Yasuhiro; Usui, Soichiro; Zhai, Peiyong; Takamura, Masayuki; Kaneko, Shuichi; Zablocki, Daniela; Yokota, Mitsuhiro; Isobe, Mitsuaki; Sadoshima, Junichi

    2014-01-01

    Background Muscle-specific RING finger protein-1 (MuRF1) is an E3 ligase that inhibits cardiac hypertrophy. However, how MuRF1 regulates cardiac hypertrophy and function during pressure overload (PO) remains poorly understood. We investigated the role of endogenous MuRF1 in regulating cardiac hypertrophy in response to PO in vivo. Methods and Results Transverse aortic constriction (TAC) for 4 weeks significantly reduced expression of MuRF1 in the mouse heart. After 2 and 4 weeks of TAC, MuRF1 knockout (Murf1?/?) mice exhibited enhanced cardiac hypertrophy and left ventricular (LV) dysfunction compared to non-transgenic (NTg) mice. Histological analyses showed that Murf1?/? mice exhibited more severe fibrosis and apoptosis than NTg mice after TAC. TAC-induced increases in the activity of a nuclear factor of activated T cells (NFAT) luciferase reporter were significantly greater in Murf1?/? than in NTg mice. TAC-induced increases in calcineurin A (CnA) expression were also significantly enhanced in Murf1?/? compared to in NTg mice. Co-immunoprecipitation assays showed that endogenous MuRF1 and CnA interact with one another. Polyubiquitination of CnA was attenuated in Murf1?/? mouse hearts at baseline and in response to TAC, and the protein stability of CnA was enhanced in cardiomyocytes in which MuRF1 was downregulated in vitro. Furthermore, MuRF1 directly ubiquitinated CnA in vitro. Cardiac-specific overexpression of ZAKI-4?, an endogenous inhibitor of CnA, significantly suppressed the enhancement of TAC-induced cardiac hypertrophy and dysfunction, as well as increases in cardiac fibrosis and apoptosis, in Murf1?/? mice. Conclusions Endogenous MuRF1 negatively regulates cardiac hypertrophy and dysfunction in response to PO through inhibition of the calcineurin-NFAT pathway. PMID:24526353

  13. Increased active elastic stiffness in tetanized papillary muscles from hypertrophied rabbit hearts.

    Science.gov (United States)

    Hultgren, P B; Hamrell, B B

    1986-01-01

    Studies of skeletal muscle suggest that the ratio of stiffness to tension will increase in the presence of a slower rate of crossbridge head rotation from the attached perpendicular state (non-force generating) to the attached 45 degree angle state (force generating). Maximum shortening velocity is depressed proportionate with adenosinetriphosphatase activity in pressure overload cardiac hypertrophy. The maximum rate of isometric force generation also is less than normal but active isometric force levels are normal. The myosin isoenzymes of hypertrophied heart muscle are shifted to predominantly slower than normal types. Among a number of possibilities, the overall rate of crossbridge cycling may be less than normal and crossbridge head rotation may be slower. We reasoned that a greater than normal ratio of active elastic stiffness to total tension development in hypertrophy would be suggestive of an alteration from normal in crossbridge dynamics. We studied right ventricular septal papillary muscles from normal rabbits and from rabbits with hypertrophy induced by pulmonary artery constriction. A high level of mechanical activation was obtained by tetanizing the muscles in solutions containing caffeine. Small (less than or equal to 2% muscle length) and rapid (0.8 ms) length perturbations were applied to the preparations with a servo-controlled motor. Active elastic stiffness was estimated from the linear relationship of minimum (for releases) or maximum (for stretches) tension reached during a length change with muscle length change (strain). Although total tetanic tension development was normal in the hypertrophied muscles (p greater than 0.1), active elastic stiffness was greater than normal in hypertrophy (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2948487

  14. Morphological and Molecular Changes of the Myocardium After Left Ventricular Mechanical Support

    OpenAIRE

    Baba, Hideo A.; Wohlschlaeger, Jeremias

    2008-01-01

    Left ventricular assist devices (LVAD) are currently used to either “bridge” patients with terminal congestive heart failure (CHF) until cardiac transplantation is possible or optionally for patients with contraindications for transplantation (“destination therapy”). Mechanical support is associated with a marked decrease of cardiac dilation and hypertrophy as well as numerous cellular and molecular changes (“reverse cardiac remodeling”), which can be accompanied by improved cardi...

  15. Altered Cardiac Myocyte Ca Regulation In Heart Failure

    Science.gov (United States)

    PhD Donald M. Bers (Stritch School of Medicine - Loyola University Chicago Physiology)

    2006-12-01

    The article explores Myocyte Ca regulation in heart failure. The article suggests that there are alterations in how myocyte Ca is regulated which causes characteristics found during heart failure. There is a lot known about this topic and this review could help further the investigation into the cause of heart failure.

  16. Myocardial disarray in Noonan syndrome

    OpenAIRE

    Burch, Michael; Mann, Jessica M.; Sharland, Michael; Shinebourne, Elliot A.; Patton, Michael A.; Mckenna, William J.

    1992-01-01

    Objective—To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy.

  17. Endothelial and non-endothelial coronary blood flow reserve and left ventricular dysfunction in systemic hypertension

    Scientific Electronic Library Online (English)

    Aloísio Marchi, Rocha; Vera Maria Cury, Salemi; Pedro Alves, Lemos Neto; Afonso Yoshikiro, Matsumoto; Valéria Fontenelle Angelim, Pereira; Fábio, Fernandes; Luciano, Nastari; Charles, Mady.

    2009-04-01

    Full Text Available OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has b [...] een proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS >0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS

  18. Some previously neglected examples of arrhythmogenic right ventricular dysplasia/cardiomyopathy and frequency of its various reported manifestations.

    Science.gov (United States)

    Roberts, William Clifford; Ko, Jong Mi; Kuiper, Johannes Jacob; Hall, Shelley Anne; Meyer, Dan Marshall

    2010-07-15

    Four patients are described with either parchment-like thinning or partial but extensive myocyte depletion with severe fatty or fibrofatty infiltration of the free wall of the right ventricle in its outflow tract, including 2 previously reported patients who also had focal parchment-like thinning of the left ventricular free wall. Three had documented ventricular tachycardia, and the remaining patient had sudden death as his first and only manifestation of heart disease. Three patients had severe heart failure: in 1, it was fatal, and the other 2 underwent cardiac transplantation. Necropsy cases of parchment-heart syndrome before 1980 are reviewed, as well as large series of cases with arrhythmogenic right ventricular dysplasia (ARVD) reported subsequently. It is suggested that ARVD is not an ideal name for this condition, because malignant ventricular arrhythmias are not universal, the left ventricular free wall and/or ventricular septum are sometimes involved, and the name "ARVD" neglects the fact that severe heart failure may be prominent in these patients. The right ventricular wall can be thin or parchment-like, or it may not be thinned but consist mainly of adipose tissue with or without focal fibrous tissue and a few islands of myocytes. Nevertheless, because the name "ARVD" has been commonly used and recognized for >30 years, it is probably best retained for this condition. PMID:20599014

  19. Patterns of left ventricular geometry and the transition to congestive heart failure with preserved versus depressed ejection fraction (Patrones de geometría ventricular izquierda y la transición a la insuficiencia cardíaca congestiva con fracción de eyección conservada versus deprimida

    Directory of Open Access Journals (Sweden)

    José H. Donis Hernández

    2014-12-01

    Full Text Available Abstract (english Analysis of cross-sectional and follow up clinical studies, of hypertensive patients with the different left ventricular geometric patterns, provide plausible explanations for the transition from hypertensive heart disease to the two distinct phenotypes of systolic and diastolic congestive heart failure. According to the LIFE study treated-uncomplicated patients, with normal ventricular geometry (12%, concentric remodeling (11 % and concentric hypertrophy (34 %, may evolve to the eccentric hypertrophy pattern. Patients with the eccentric hypertrophy pattern have selective sympathetic activation and progressive enlargement of the left ventricular cavity with thinning of its walls. This pattern goes on to a stage of systolic dysfunction with diminished ejection fraction and enhanced degradation of the collagen matrix. On the other hand, patients with the concentric hypertrophy pattern have predominant activation of the renin-angiotensin-aldosterone system and progressive shrinking of the left ventricular cavity with thickening of its walls. This pattern usually precedes the stage of diastolic heart failure with preserved ejection fraction, impairment of relaxation and increased deposition of collagen in the myocardial interstitium. Thus, ventricular remodeling preceding diastolic heart failure is opposite to that of hypertensive patients who go on to develop systolic heart failure. Resumen (español El análisis de los estudios transversales y longitudinales, de pacientes hipertensos con diferentes patrones de geometría ventricular izquierda, permite postular posibles mecanismos fisiopatológicos para explicar la transición de la cardiopatía hipertensiva hacia los dos fenotipos conocidos de insuficiencia cardiaca. De acuerdo con el estudio LIFE, los pacientes hipertensos no complicados, con patrones de geometría ventricular normal (12 %, remodelado concéntrico (11 % e hipertrofia concéntrica (34 %, pueden evolucionar hacia la hipertrofia excéntrica. Pacientes con este último patrón geométrico se caracterizan por tener activación simpática y aumento progresivo aumento del tamaño de la cavidad ventricular con disminución del espesor relativo de sus paredes. El deterioro de la función ventricular y la degradación del colágeno intersticial predisponen a la insuficiencia cardiaca con función sistólica deprimida. Por el contrario, los pacientes con hipertrofia ventricular concéntrica tienen activación del sistema renina-angiotensina-aldosterona y aumento progresivo del grosor de las paredes ventriculares, sin cambios en el tamaño de la cavidad. La aparición, de los síntomas de insuficiencia cardiaca, se acompaña de alteraciones de la distensibilidad ventricular, aumento en la síntesis del colágeno intersticial y función ventricular sistólica normal. En otras palabras, las alteraciones progresivas de la geometría y de la función ventricular izquierda, que preceden a la aparición de los síntomas y signos de insuficiencia cardiaca, permiten explicar la transición de la cardiopatía hipertensiva hacia la insuficiencia cardiaca con función ventricular normal o anormal.

  20. Ventricular torsional relation to ventricular fiber arrangement

    CERN Document Server

    Ranjbar, Saeed; Meybodi, Mahmood Emami

    2014-01-01

    Left ventricular torsion from helically oriented myofibers is a key parameter of cardiac performance. Physicians observing heart motion on echocardiograms, during cardiac catheterization, or in the operating room, are impressed by the twisting or rotary motion of the left ventricle during systole. Conceptually, the heart has been treated as a pressure chamber. The rotary or torsional deformation has been poorly understood by basic scientists and has lacked clinical relevance. The aim of this paper attempts to discuss about this question: Is ventricular twisting related to ventricular fiber arrangement? That is dependent to an assumed model of the left ventricular structure.

  1. Fibrose miocárdica e remodelamento ventricular na insuficiência aórtica crônica importante / Myocardial fibrosis and ventricular remodeling in severe chronic aortic regurgitation / Fibrosis miocárdica y remodelación ventricular en la insuficiencia aórtica crónica severa

    Scientific Electronic Library Online (English)

    Nelson, Elias; Flávio, Tarasoutchi; Guilherme Sobreira, Spina; Roney O., Sampaio; Pablo M. A., Pomerantzeff; Francisco Rafael, Laurindo; Max, Grinberg.

    2009-01-01

    Full Text Available FUNDAMENTO: A insuficiência aórtica crônica importante sintomática (IAo) leva a grande remodelamento ventricular esquerdo, à custa de hipertrofia de mióciotos e remodelamento da matriz extracelular. A relevância da concentração de fibrose intersticial nos pacientes acometidos é desconhecida. Analisa [...] mos o grau de fibrose no ventrículo esquerdo (VE) em pacientes sintomáticos com IAo submetidos a tratamento cirúrgico e sua relação com características funcionais e anatômicas. OBJETIVO: Avaliar a fibrose miocárdica na insuficiência aórtica crônica importante. MÉTODOS: Selecionaram-se 28 pacientes com IAo (16 com função VE normal e 12 com disfunção do VE), os quais foram analisados no pré e pós-operatório por ecodopplercardiografia. A capacidade funcional foi medida pelo teste de esforço cardiopulmonar. Para comparação dos resultados histopatológicos, um grupo-controle de 9 pacientes foi constituído. RESULTADOS: A média etária foi de 39 ± 12 anos, 75% do sexo masculino com 84% de etiologia reumática. Vinte e cinco pacientes permaneceram em classes funcionais I e II ao fim do estudo e apresentaram redução significativa dos diâmetros do VE entre os momentos pré e pós-operatórios. Houve três óbitos não relacionados à disfunção VE. Os parâmetros do teste cardiopulmonar não se modificaram entre o pré e o pós-operatório. O volume de fibrose intersticial em pacientes com IAo foi significativamente quando maior comparado ao grupo controle (3,47 ± 1,9% vs 0,82 ± 0,96%, respectivamente, p = 0,001). Não houve correlação entre o grau de fibrose do VE, parâmetros ecocardiográficos e funcionais. CONCLUSÃO: Em pacientes com IAo, a presença de fibrose miocárdica não se associou às alterações clínicas, ecocardiográficas ou funcionais. Abstract in spanish FUNDAMENTO: La insuficiencia aórtica crónica severa sintomática (IAo crónica severa) ocasiona una gran remodelación ventricular izquierda, por cuenta de hipertrofia de miociotos y remodelación de la matriz extracelular. Se desconoce la relevancia de la concentración de fibrosis intersticial en los p [...] acientes acometidos. Analizamos el grado de fibrosis en el ventrículo izquierdo (VI) en pacientes sintomáticos con IAo crónica severa sometidos a tratamiento quirúrgico y su relación con características funcionales y anatómicas. OBJETIVO: Evaluar la fibrosis miocárdica en la insuficiencia aórtica crónica severa. MÉTODOS: Se seleccionaron a 28 pacientes con IAo crónica severa (16 con función VI normal y 12 con disfunción del VI), los que se analizaron en el pre y el postoperatorio por ecocardiografía Doppler. Se midió la capacidad funcional por la prueba de esfuerzo cardiopulmonar. Para comparación de los resultados histopatológicos, se constituyó a un Grupo Control de 9 pacientes. RESULTADOS: El promedio de edad fue de 39±12 años, el 75% del sexo masculino con el 84% de etiología reumática. El total de 25 pacientes permanecieron en clases funcionales I e II al fin del estudio y presentaron reducción significativa de los diámetros del VI entre los momentos pre y postoperatorios. Hubo tres óbitos no relacionados a la disfunción VI. Los parámetros de la prueba cardiopulmonar no se modificaron entre el pre y el postoperatorio. El volumen de fibrosis intersticial en pacientes con IAo crónica severa fue significativo cuando mayor, comparado al Grupo control (3,47 ± 1,9% vs. 0,82 ±0,96%, respectivamente, p = 0,001). No hubo correlación entre el grado de fibrosis del VI, parámetros ecocardiográficos y funcionales. CONCLUSIÓN: En pacientes con IAo crónica severa, la presencia de fibrosis miocárdica no se asoció a las alteraciones clínicas, ecocardiográficas o funcionales. Abstract in english BACKGROUND: Significant symptomatic chronic aortic regurgitation (AR) leads to considerable left ventricular remodeling at the expense of myocyte hypertrophy and extracellular matrix remodeling. The relevance of interstitial fibrosis concentration in these patients is unk

  2. Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

    OpenAIRE

    Isoyama, S.; Ito, N; Kuroha, M; Takishima, T.

    1989-01-01

    Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. ...

  3. Differential structure of atrial and ventricular KATP: atrial KATP channels require SUR1

    OpenAIRE

    Flagg, Thomas P.; Kurata, Harley T.; Masia, Ricard; Caputa, George; Magnuson, Mark A.; Lefer, David J.; Coetzee, William A.; Nichols, Colin G.

    2008-01-01

    The isoform–specific structure of the ATP-sensitive potassium (KATP) channel endows it with differential fundamental properties, including physiological activation and pharmacology. Numerous studies have convincingly demonstrated that the pore-forming Kir6.2 (KCNJ11) and regulatory SUR2A (ABCC9) subunits are essential elements of the sarcolemmal KATP channel in cardiac ventricular myocytes. Using a novel antibody directed against the COOH-terminus of SUR1 (ABCC8), we show that this KATP sub...

  4. Regulation of Ca2+ current in frog ventricular cardiomyocytes by guanosine 5'-triphosphate analogues and isoproterenol

    OpenAIRE

    1993-01-01

    Calcium currents (ICa) were measured in frog ventricular myocytes using the whole-cell patch clamp technique and a perfused pipette. To gain insight into the role of G proteins in the regulation of ICa in intact cells, the effect of internal perfusion with hydrolysis-resistant GTP analogues, guanylyl 5'-imidodiphosphate (GppNHp) or guanosine 5'- thiotriphosphate (GTP gamma S), on ICa stimulated by isoproterenol (Iso) or forskolin (Forsk) was examined. Significant differences were observed bet...

  5. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Scientific Electronic Library Online (English)

    A., Medeiros; E.M., Oliveira; R., Gianolla; D.E., Casarini; C.E., Negrão; P.C., Brum.

    1909-19-01

    Full Text Available The effect of swimming training (ST) on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12) and trained (T, N = 12) male Wistar rats (200-220 g). ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect [...] of the autonomic nervous system in generating training-induced resting bradycardia (RB) was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm). RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm), since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13%) and myocyte dimension (21%) were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  6. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    Medeiros A.

    2004-01-01

    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  7. Microvasculature in angiotensin II-dependent cardiac hypertrophy in the rat.

    Science.gov (United States)

    Sabri, A; Samuel, J L; Marotte, F; Poitevin, P; Rappaport, L; Levy, B I

    1998-08-01

    The long-lasting effect of angiotensin II (Ang II) on the microvasculature in the rat left ventricle was studied. Immunolabeling of ventricular cryosections combined with morphometric analysis allowed us to (1) distinguish between capillaries and arterioles and (2) precisely evaluate their respective densities in the endomyocardium. Ang II-induced hypertensive cardiac hypertrophy was associated with an 18% decrease in capillary density (P<0.05) and an increase in arteriole density (+54%, P<0.001). Treatments with losartan or PD123319, the respective antagonists of the angiotensin subtype 1 and subtype 2 receptors, prevented the increase in arteriolar density, whereas only losartan, which restored normal arterial pressure, prevented changes in capillary density. Taken together, these results indicate that Ang II-induced cardiac hypertrophy was associated with capillary rarefaction and arteriolar growth, the 2 processes being independently regulated. PMID:9719070

  8. Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Carillon, Julie; Rugale, Caroline; Rouanet, Jean-Max; Cristol, Jean-Paul; Lacan, Dominique; Jover, Bernard

    2014-08-01

    We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy. PMID:24601674

  9. Ventricular septal defect (image)

    Science.gov (United States)

    Ventricular septal defect is a congenital defect of the heart, that occurs as an abnormal opening in the wall that separates the right and left ventricles. Ventricular septal defect may also be associated with other heart ...

  10. Self-protection by cardiac myocytes against hypoxia and hyperoxia.

    Science.gov (United States)

    Winegrad, S; Henrion, D; Rappaport, L; Samuel, J L

    1999-10-15

    Cardiac muscle must maintain a continuous balance between its energy supply and work performed. An important mechanism involved in achievement of this balance is cross talk via chemical signals between cardiac myocytes and the cardiac muscle vascular system. This has been demonstrated by incubating isolated cardiac myocytes in different concentrations of oxygen and then assaying the conditioned media for vasoactive substances on isolated aortic rings and small-resistance arteries. With increasing oxygen concentrations above 6%, cardiac myocytes produce increasing amounts of angiotensin I, which is converted to angiotensin II by the blood vessel. The angiotensin II stimulates vascular endothelial cells to secrete endothelin and increase vascular tone. Below 6% oxygen, cardiac myocytes secrete adenosine, which acts directly on vascular smooth muscle to block the effect of alpha-adrenergic agonists and reduce vascular tone. In an intact heart, the net effect of these 2 regulatory systems would be the maintenance of oxygen concentration within a narrow range at the cardiac myocytes. By acting as oxygen sensors, cardiac myocytes modulate vascular tone according to the needs of the myocytes and reduce potential problems of hypoxia and extensive formation of reactive oxygen species. PMID:10521242

  11. Genital hypertrophy: A neonatal pseudotumor in females

    International Nuclear Information System (INIS)

    A newborn female presented with a perineal and pelvic pseudotumor due to genital hypertrophy. This entity should not be confused with interlabial or cul-de-sac masses that require surgical intervention. (orig.)

  12. Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs.

    Science.gov (United States)

    Dell'italia, L J; Balcells, E; Meng, Q C; Su, X; Schultz, D; Bishop, S P; Machida, N; Straeter-Knowlen, I M; Hankes, G H; Dillon, R; Cartee, R E; Oparil, S

    1997-08-01

    We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy prevents volume-overload hypertrophy in dogs with chronic mitral regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally, twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after induction of MR. Cine-magnetic resonance imaging demonstrated that left ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P dissolution collagen weave in both N-MR and R-MR hearts may be related to the stretch of volume overload. PMID:9277516

  13. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    International Nuclear Information System (INIS)

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6±1.6 vs. 4.1±0.5, p<0.01) and posterolateral wall (5.9±0.7 vs. 3.8±0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference inar shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  14. Calcineurin signalling mechanisms in myocardial hypertrophy

    Directory of Open Access Journals (Sweden)

    Jian-Chun Wang

    2010-12-01

    Full Text Available Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitutively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE (2000-2011, systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy.

  15. AMPK attenuates microtubule proliferation in cardiac hypertrophy

    OpenAIRE

    Fassett, John T.; Hu, Xinli; Xu, Xin; Lu, Zhongbing; Zhang, Ping; Chen, Yingjie; Bache, Robert J.

    2013-01-01

    Cell hypertrophy requires increased protein synthesis and expansion of the cytoskeletal networks that support cell enlargement. AMPK limits anabolic processes, such as protein synthesis, when energy supply is insufficient, but its role in cytoskeletal remodeling is not known. Here, we examined the influence of AMPK in cytoskeletal remodeling during cardiomyocyte hypertrophy, a clinically relevant condition in which cardiomyocytes enlarge but do not divide. In neonatal cardiomyocytes, activati...

  16. Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy.

    Science.gov (United States)

    Jaffré, Fabrice; Bonnin, Philippe; Callebert, Jacques; Debbabi, Haythem; Setola, Vincent; Doly, Stéphane; Monassier, Laurent; Mettauer, Bertrand; Blaxall, Burns C; Launay, Jean-Marie; Maroteaux, Luc

    2009-01-01

    By mimicking sympathetic stimulation in vivo, we previously reported that mice globally lacking serotonin 5-HT(2B) receptors did not develop isoproterenol-induced left ventricular hypertrophy. However, the exact cardiac cell type(s) expressing 5-HT(2B) receptors (cardiomyocytes versus noncardiomyocytes) involved in pathological heart hypertrophy was never addressed in vivo. We report here that mice expressing the 5-HT(2B) receptor solely in cardiomyocytes, like global 5-HT(2B) receptor-null mice, are resistant to isoproterenol-induced cardiac hypertrophy and dysfunction, as well as to isoproterenol-induced increases in cytokine plasma-levels. These data reveal a key role of noncardiomyocytes in isoproterenol-induced hypertrophy in vivo. Interestingly, we show that primary cultures of angiotensinogen null adult cardiac fibroblasts are releasing cytokines on stimulation with either angiotensin II or serotonin, but not in response to isoproterenol stimulation, demonstrating a critical role of angiotensinogen in adrenergic-dependent cytokine production. We then show a functional interdependence between AT(1)Rs and 5-HT(2B) receptors in fibroblasts by revealing a transinhibition mechanism that may involve heterodimeric receptor complexes. Both serotonin- and angiotensin II-dependent cytokine production occur via a Src/heparin-binding epidermal growth factor-dependent transactivation of epidermal growth factor receptors in cardiac fibroblasts, supporting a common signaling pathway. Finally, we demonstrate that 5-HT(2B) receptors are overexpressed in hearts from patients with congestive heart failure, this overexpression being positively correlated with cytokine and norepinephrine plasma levels. Collectively, these results reveal for the first time that interactions between AT(1) and 5-HT(2B) receptors coexpressed by noncardiomyocytes are limiting key events in adrenergic agonist-induced, angiotensin-dependent cardiac hypertrophy. Accordingly, antagonists of 5-HT(2B) receptors might represent novel therapeutics for sympathetic overstimulation-dependent heart failure. PMID:19023134

  17. Measuring Ca2+ sparks in cardiac myocytes.

    Science.gov (United States)

    Macquaide, Niall; Bito, Virginie; Sipido, Karin R

    2015-01-01

    This protocol describes the measurement of Ca(2+) sparks in intact myocytes by using a Ca(2+)-sensitive dye and imaging using laser scanning confocal microscopy. It takes advantage of spontaneous Ca(2+)-release events-sparks-using them as a measure of the activity of ryanodine receptors (RyRs). Two methodologies are described: One requires that cardiomyocytes be stimulated, preferably under voltage clamp by depolarizing pulses, until steady-state is reached, and then stimulation is stopped and Ca(2+) sparks are recorded. The second requires that cells be permeabilized and bathed in a solution to load the cell with Ca(2+) sufficient to elicit Ca(2+) sparks, but not Ca(2+) waves. These are then analyzed offline to quantify spark frequency and morphology. The advantages and disadvantages of each approach are discussed. PMID:25934930

  18. Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

    Scientific Electronic Library Online (English)

    F.S., Evangelista; P.C., Brum; J.E., Krieger.

    1751-17-01

    Full Text Available Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- [...] vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%). Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58%) only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25%) and myocyte dimension (13-20%) increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

  19. Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    F.S. Evangelista

    2003-12-01

    Full Text Available Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%. Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58% only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25% and myocyte dimension (13-20% increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

  20. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  1. Fate of dynamic left ventricular outflow tract obstruction after anatomic correction of transposition of the great arteries.

    Science.gov (United States)

    Yacoub, M H; Arensman, F W; Keck, E; Radley-Smith, R

    1983-09-01

    Fourteen patients undergoing successful anatomic correction for transposition of the great arteries had subpulmonary gradients of 20 to 120 mm Hg (mean 40) across the left ventricular outflow tract before surgery. Ten patients had an intact ventricular septum, and four had an additional ventricular septal defect. In one patient obstruction was due to ballooning of the septal leaflet of the tricuspid valve through the ventricular septal defect. In the remaining patients obstruction was due to bulging of the interventricular septum plus or minus septal hypertrophy and with or without a fibromuscular shelf. At operation the pulmonary valve was normal and the left ventricular outflow tract was of adequate dimension with no organic obstruction. No attempt at surgical widening was made. After surgery abnormalities revealed by echocardiography were immediately reversed. Routine reinvestigation 6 to 26 months after surgery in 10 patients showed no gradient across the left ventricular outflow tract and normal development of this region. PMID:6872196

  2. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

    DEFF Research Database (Denmark)

    Seo, Kinya; Rainer, Peter P

    2014-01-01

    Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain- or loss-of-function studies support contributions to hypertrophy and dysfunction. Selective small-molecule inhibitors remain scarce, and none target both channels, which may be useful given the high homology among them and evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II or endothelin-1 in HEK293T cells as well as in neonatal and adult cardiac myocytes. In vivo efficacy in mice and rats was greatly limited by rapid metabolism and high protein binding, although antifibrotic effects with pressure overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6 alone did not protect against hypertrophy or dysfunction from pressure overload, combined deletion was protective, supporting the value of dual inhibition. Further development of this pharmaceutical class may yield a useful therapeutic agent for heart disease management.

  3. Postural control in women with breast hypertrophy

    Directory of Open Access Journals (Sweden)

    Alessandra Ferreira Barbosa

    2012-07-01

    Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairment of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

  4. Postural control in women with breast hypertrophy

    Scientific Electronic Library Online (English)

    Alessandra Ferreira, Barbosa; Gabriela Cristina, Raggi; Cristina dos Santos Cardoso, Sá; Márcio Paulino, Costa; Jonas Eraldo de, Lima Jr.; Clarice, Tanaka.

    2012-07-01

    Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairmen [...] t of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

  5. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats.

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pechá?ová, Olga; Pelouch, Václav; Kraj?írovi?ová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Ro?. 27, Suppl.6 (2009), S5-S10. ISSN 0263-6352 R&D Projects: GA ?R GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  6. Cardiac-specific overexpression of AT1 receptor mutant lacking G?q/G?i coupling causes hypertrophy and bradycardia in transgenic mice

    Science.gov (United States)

    Zhai, Peiyong; Yamamoto, Mitsutaka; Galeotti, Jonathan; Liu, Jing; Masurekar, Malthi; Thaisz, Jill; Irie, Keiichi; Holle, Eric; Yu, Xianzhong; Kupershmidt, Sabina; Roden, Dan M.; Wagner, Thomas; Yatani, Atsuko; Vatner, Dorothy E.; Vatner, Stephen F.; Sadoshima, Junichi

    2005-01-01

    Ang II type 1 (AT1) receptors activate both conventional heterotrimeric G protein–dependent and unconventional G protein–independent mechanisms. We investigated how these different mechanisms activated by AT1 receptors affect growth and death of cardiac myocytes in vivo. Transgenic mice with cardiac-specific overexpression of WT AT1 receptor (AT1-WT; Tg-WT mice) or an AT1 receptor second intracellular loop mutant (AT1-i2m; Tg-i2m mice) selectively activating G?q/G?i-independent mechanisms were studied. Tg-i2m mice developed more severe cardiac hypertrophy and bradycardia coupled with lower cardiac function than Tg-WT mice. In contrast, Tg-WT mice exhibited more severe fibrosis and apoptosis than Tg-i2m mice. Chronic Ang II infusion induced greater cardiac hypertrophy in Tg-i2m compared with Tg-WT mice whereas acute Ang II administration caused an increase in heart rate in Tg-WT but not in Tg-i2m mice. Membrane translocation of PKC?, cytoplasmic translocation of G?q, and nuclear localization of phospho-ERKs were observed only in Tg-WT mice while activation of Src and cytoplasmic accumulation of phospho-ERKs were greater in Tg-i2m mice, consistent with the notion that G?q/G?i-independent mechanisms are activated in Tg-i2m mice. Cultured myocytes expressing AT1-i2m exhibited a left and upward shift of the Ang II dose-response curve of hypertrophy compared with those expressing AT1-WT. Thus, the AT1 receptor mediates downstream signaling mechanisms through G?q/G?i-dependent and -independent mechanisms, which induce hypertrophy with a distinct phenotype. PMID:16276415

  7. Septal myocardial protection during cardiac surgery for prevention of right ventricular dysfunction

    Directory of Open Access Journals (Sweden)

    Gerald Buckberg

    2008-11-01

    Full Text Available Postoperative right ventricular (RV failure is difficult to treat and develops from functional impairment of the underlying free wall and septum. This report describes the vital importance of the ventricular septum in RV structure /function relationships, demonstrates how the helical ventricular myocardial band model defines spatial geometry of the free wall and septum to provide architectural reasons for RV dynamic action, and focuses upon pathophysiologic reasons for adverse perioperative events resulting in right ventricular failure. Myocyte fiber orientation is the key to ventricular performance in health and disease. The transverse geometry of the free wall allows constriction (bellows type motion, whereas oblique septal fiber orientation and midline septal position is essential for ventricular twisting, the vital mechanism for RV ejection against increased pulmonary vascular resistance. The septum is considered “the lion or motor of RV performance”. This central muscle mass occupies ~40% of myocardial ventricular weight, and injury from impaired myocardial protection is a preventable event. Septal function should be the index of adequacy of myocardial protection and we will show echocardiographic evidence that the integrated cardioplegic method prevents its injury. Dysfunction of a normally functioning septum following surgical cardiac procedures calls for reevaluation of myocardial protection methods.

  8. Rol del óxido nítrico en la hipertrofia arteriolar pulmonar y ventricular cardiaca derecha en pollos a nivel del mar y expuestos a Hipoxia de la altura: The role of nitric oxide in pulmonary arteriolar and right heart ventricle hypertrophy in chickens at sea level and exposed to high altitude Hypoxia

    Scientific Electronic Library Online (English)

    María, Vásquez C.; Sergio, Cueva M.; Boris, Lira M.; Milder, Ayón S.; José, Rodríguez G.; Pedro, Angulo H.; Néstor, Falcón P..

    Full Text Available El objetivo del presente estudio fue determinar los valores de nitritos y nitratos, metabolitos estables del óxido nítrico (ON), y su correlación con el grado de hipertrofia arteriolar pulmonar en aves sometidas a hipoxia ambiental. Se emplearon 135 aves machos de la línea Cobb-Vantres, nacidos a ni [...] vel del mar. De estas, 120 fueron divididos en dos grupos: 60 aves criadas a nivel del mar (NM) y 60 aves criadas en altura a 3320 msnm (A), en tanto que las 15 aves restantes fueron sacrificadas al primer día de edad. Quince aves seleccionadas al azar de cada grupo fueron sacrificadas a los 10, 20, 30 y 40 días de edad. Se determinó el peso corporal (PC), hematocrito (Ht), nitritos y nitratos, relación capa muscular/diámetro arteriolar pulmonar (CM/DA), relación peso del ventrículo derecho/ peso total del ventrículo (VD/VT), y relación peso ventrículo derecho/peso corporal (VD/PC). El PC fue mayor a NM que en A (p Abstract in english The aim of this study was to determine the nitrites and nitrates concentration, stable metabolites of NO, and its correlation with the degree of pulmonary arteriole hypertrophy in chickens raised at environmental hypoxia. A total of 135 Cobb-Vantres male chickens, born at sea level were used. Of thi [...] s, 60 chicks raised at sea level (SL), and 60 at high altitude (A), 3230 m above sea level; while the remaining 15 birds were slaughtered at 1 day of age. Fifteen 15 chicks per group were randomly selected and slaughtered at 10, 20, 30 and 40 days of age. It was determined body weight (BW), hematocrite (Ht), nitrites and nitrates, muscular wall/arteriolar diameter (CM/DA) ratio, right ventricle weight/total ventricle weight ratio (RV/TV), and right ventricle weight/body weight ratio (RV/BW) ratio. BW was greater at SL than at A (p

  9. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    International Nuclear Information System (INIS)

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present

  10. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45Ca tracer measurements after loading the myocytes with 45Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect

  11. Calcium-voltage coupling in the genesis of early and delayed afterdepolarizations in cardiac myocytes.

    Science.gov (United States)

    Song, Zhen; Ko, Christopher Y; Nivala, Michael; Weiss, James N; Qu, Zhilin

    2015-04-21

    Early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs) are voltage oscillations known to cause cardiac arrhythmias. EADs are mainly driven by voltage oscillations in the repolarizing phase of the action potential (AP), while DADs are driven by spontaneous calcium (Ca) release during diastole. Because voltage and Ca are bidirectionally coupled, they modulate each other's behaviors, and new AP and Ca cycling dynamics can emerge from this coupling. In this study, we performed computer simulations using an AP model with detailed spatiotemporal Ca cycling incorporating stochastic openings of Ca channels and ryanodine receptors to investigate the effects of Ca-voltage coupling on EAD and DAD dynamics. Simulations were complemented by experiments in mouse ventricular myocytes. We show that: 1) alteration of the Ca transient due to increased ryanodine receptor leakiness and/or sarco/endoplasmic reticulum Ca ATPase activity can either promote or suppress EADs due to the complex effects of Ca on ionic current properties; 2) spontaneous Ca waves also exhibit complex effects on EADs, but cannot induce EADs of significant amplitude without the participation of ICa,L; 3) lengthening AP duration and the occurrence of EADs promote DADs by increasing intracellular Ca loading, and two mechanisms of DADs are identified, i.e., Ca-wave-dependent and Ca-wave-independent; and 4) Ca-voltage coupling promotes complex EAD patterns such as EAD alternans that are not observed for solely voltage-driven EADs. In conclusion, Ca-voltage coupling combined with the nonlinear dynamical behaviors of voltage and Ca cycling play a key role in generating complex EAD and DAD dynamics observed experimentally in cardiac myocytes, whose mechanisms are complex but analyzable. PMID:25902431

  12. Interaction of the renin-angiotensin system and the endothelin system in cardiac hypertrophy.

    Science.gov (United States)

    Stula, M; Pinto, Y M; Gschwend, S; Teisman, A C; van Gilst, W H; Böhm, M; Dietz, R; Paul, M

    1998-01-01

    It has been suggested that the renin-angiotensin system (RAS) interacts with the endothelin system in the pathogenesis of cardiac remodeling. We examined endothelin system regulation in a model of chronic RAS dysfunction, which is believed to be an important factor in cardiac remodeling. We used the transgenic rat line TGR(mRen2)27, which overexpresses the mouse Renin-2 gene and shows hypertension and left ventricular hypertrophy compared to Sprague-Dawley (SD) rats. Ren-2 rats (n = 24) received either losartan (LOS), quniapril (QIN), or carvedilol (CARV) for 11 weeks, or no treatment. After 11 weeks left (LV) and right ventricular (RV) weights were determined and total RNA extracted. Ren-2 rats showed a mean systolic blood pressure of 190 mm (+/- SEM), which could be normalized to 110 +/- mm (+/- SEM) by treatment with LOS or QIN. CARV also reduced blood pressure but did not normalize it. LV end-diastolic pressure was normal in both SD and Ren-2 rats. LV weight was increased in the Ren-2 rats compared to SD rats, and was significantly reduced to normal in the LOS and QIN but not in the CARV group. RV weight was normal in all groups. Northern blot analysis of preproendothelin-1 (preproET-1) and endothelin-converting enzyme-1 (ECE-1) expression revealed a significant (p CARV, induced preproET-1 transcription by threefold (p CARV and LOS group and was decreased by 20% in the QIN group. Similar changes in LV and RV indicated a direct influence of a dysregulated RAS on the endothelin system. In conclusion, the activated RAS downregulates the endothelin system in this model of cardiac hypertrophy. This suggests that in chronic RAS activated, the endothelin system may have a different pathophysiologic impact as a co-factor leading to cardiac hypertrophy. PMID:9595497

  13. Carpal tunnel syndrome: an unusual presentation of brachial hypertrophy.

    OpenAIRE

    Shenoy, K. T.; Saha, P K; M. Ravindran

    1980-01-01

    A patient with carpal tunnel syndrome in association with congenital hypertrophy of right upper limb is described. The median nerve also showed hypertrophy. The symptoms were relieved by decompression of the carpal tunnel.

  14. Bases moleculares de la hipertrofia ventricular izquierda: papel del estrés oxidativo

    Directory of Open Access Journals (Sweden)

    Félix Broche Valle

    1997-12-01

    Full Text Available La hipertensión arterial (HTA como enfermedad primaria es una de las primeras causas de morbilidad y mortalidad general en muchos países. La cardiopatía isquémica y otras formas clínicas de la enfermedad cardiovascular aterosclerótica se presentan con mayor frecuencia en los pacientes hipertensos. La aparición y severidad de las manifestaciones de isquemia miocárdica se incrementan si coexiste hipertrofia ventricular izquierda. En el miocardio hipertrófico se producen eventos de isquemia/reperfusión durante cada ciclo cardíaco. En estas condiciones, diversos factores conducen al estrés oxidativo cuyas consecuencias se expresan por alteraciones morfofuncionales en el corazón y otros sistemas. En este trabajo se presentan los principales mecanismos conocidos que aportan las bases moleculares de la hipertrofia ventricular y de la pared arterial en los pacientes hipertensos, así como el origen y significado fisiopatológico del estrés oxidativo en esta entidad con el propósito de contribuir a la sustentación teórica de los criterios para diagnóstico, pronóstico, evolución y tratamiento del paciente hipertenso con hipertrofia ventricular izquierda.Arterial hypertension (AHT as a primary disease is one of the first causes of morbidity and general mortality in many countries. Ischemic cardiopathy and other clinical forms of the atherosclerotic cardiovascular disease are more common among hypertensives. The appearance and severity of the manifestations of myocardial infarction increase if left ventricular hypertrophy coexists. In the hypertrophic myocardium, events of ischemia/reperfusion take place during each cardiac cycle. Under these conditions, different factors lead to the oxidative stress, whose consequences are expressed by morph ofunctional alterations of the heart and other systems. In this paper, the main mechanisms giving molecular bases of ventricular hypertrophy ahod of the arterial wall in hypertensives, as well as the origin and physiopathologic significance of the oxidative stress in this disease, are presented aimed at contributing to the theoretical support of the criteria for diagnosis, prognosis, evolution and treatment of the hypertensive patient suffering from left ventricular hypertrophy.

  15. Bases moleculares de la hipertrofia ventricular izquierda: papel del estrés oxidativo

    Scientific Electronic Library Online (English)

    Félix, Broche Valle; Marisol, Peña Sánchez; Ela M, Céspedes Miranda; José C, García Piñeiro; José, Castillo Herrera.

    1997-12-01

    Full Text Available La hipertensión arterial (HTA) como enfermedad primaria es una de las primeras causas de morbilidad y mortalidad general en muchos países. La cardiopatía isquémica y otras formas clínicas de la enfermedad cardiovascular aterosclerótica se presentan con mayor frecuencia en los pacientes hipertensos. [...] La aparición y severidad de las manifestaciones de isquemia miocárdica se incrementan si coexiste hipertrofia ventricular izquierda. En el miocardio hipertrófico se producen eventos de isquemia/reperfusión durante cada ciclo cardíaco. En estas condiciones, diversos factores conducen al estrés oxidativo cuyas consecuencias se expresan por alteraciones morfofuncionales en el corazón y otros sistemas. En este trabajo se presentan los principales mecanismos conocidos que aportan las bases moleculares de la hipertrofia ventricular y de la pared arterial en los pacientes hipertensos, así como el origen y significado fisiopatológico del estrés oxidativo en esta entidad con el propósito de contribuir a la sustentación teórica de los criterios para diagnóstico, pronóstico, evolución y tratamiento del paciente hipertenso con hipertrofia ventricular izquierda. Abstract in english Arterial hypertension (AHT) as a primary disease is one of the first causes of morbidity and general mortality in many countries. Ischemic cardiopathy and other clinical forms of the atherosclerotic cardiovascular disease are more common among hypertensives. The appearance and severity of the manife [...] stations of myocardial infarction increase if left ventricular hypertrophy coexists. In the hypertrophic myocardium, events of ischemia/reperfusion take place during each cardiac cycle. Under these conditions, different factors lead to the oxidative stress, whose consequences are expressed by morph ofunctional alterations of the heart and other systems. In this paper, the main mechanisms giving molecular bases of ventricular hypertrophy ahod of the arterial wall in hypertensives, as well as the origin and physiopathologic significance of the oxidative stress in this disease, are presented aimed at contributing to the theoretical support of the criteria for diagnosis, prognosis, evolution and treatment of the hypertensive patient suffering from left ventricular hypertrophy.

  16. VENTRICULAR ARRHYTHMIAS IN CHILDHOOD

    Directory of Open Access Journals (Sweden)

    AL Sami

    2005-01-01

    Full Text Available Isolated premature ventricular beats may be seen in 15% of normal newborns, 30% of normal adolescents and 66% of adolescents with repaired heart disease. Sustained ventricular arrhythmias are relatively rare în young normal hearts. Sudden cardiac death is also rare în young with normal hearts, although there is an increased incidence in dilated and hypertrophic cardiomyopathies and following repair of particular congenital heart lesions.Patients with cardiomyopathy (CM often have ventricular arrhythmias, although the risk of mortality is more closely linked to ventricular function. There are many infants and pediatric patients with apparently normal hearts who have asymptomatic nonsustained ventricular tachycardia.The main concern is to identify diagnoses such as long QT syndrome associated with recurrent cardiac syncope so that appropriate choices can be made regarding drug and/or device therapy.

  17. Association between inhibition of arachidonic acid release and prevention of calcium loading during ATP depletion in cultured rat cardiac myocytes

    International Nuclear Information System (INIS)

    The development of irreversible myocardial ischemic injury is associated with progressive degradation of membrane phospholipids, accumulation of arachidonate and other free fatty acids, and electrolyte derangements, including calcium accumulation. To study the relationship between arachidonate release and calcium loading during adenosine triphosphate (ATP) depletion in cardiac myocytes, the effects of two purported phospholipase inhibitors, mepacrine and U26,384, were evaluated. Cultured neonatal rat ventricular myocytes were pretreated for 90 minutes with 5 to 10 microM U26,384 (a steroidal diamine) or 10 to 50 microM mepacrine (an alkyl acridine) and then treated for 3 hours with 30 microM of the metabolic inhibitor, iodoacetic acid (IAA), with or without an additional dose of drug. IAA treatment resulted in a marked reduction in ATP level and a several-fold increase in free fatty acid radioactivity released from myocytes prelabeled with tritiated arachidonic acid (3H-AA). U26,384 produced substantial inhibition of the increased 3H-AA release, and was effective when given as a single pretreatment dose before IAA exposure or as continuous treatment before and during IAA exposure (for example, with 5 microM U26,384, the percentage of 3H-AA release versus IAA alone was 8% +/- 2% [SEM] [N = 15] for pretreatment only and 13% +/- 4% [N = 10] for continuous treatment). Mepacrine also resulted in significant reduction in 3H-AA release, but was more effective when given as cse, but was more effective when given as continuous treatment (for example, with 50 microM mepacrine, the percentage of 3H-AA release versus IAA alone was 43% +/- 9% [N = 6] for pretreatment only and 22% +/- 7% [N = 9] for continuous treatment). More detailed analysis showed that U26,384 and mepacrine blocked the IAA-induced redistribution of 3H-AA into free fatty acids from other lipid species

  18. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  19. Mechanisms by which calcium receptor stimulation modifies electromechanical coupling in isolated ventricular cardiomyocytes.

    Science.gov (United States)

    Schreckenberg, Rolf; Dyukova, Elena; Sitdikova, Guzel; Abdallah, Yaser; Schlüter, Klaus-Dieter

    2015-02-01

    The calcium-sensing receptor (CaR) is widely expressed throughout the entire cardiovascular system and is capable of activating signaling pathways in different cells. Alongside calcium, the CaR also responds to physiological polycations such as putrescine underlining a participation in physiological and pathophysiological processes. Here, we aimed to determine mechanisms as to how CaR activation affects the contractile responsiveness of ventricular cardiomyocytes under basal and stimulated conditions. For that purpose, cardiac myocytes from 3-month-old male Wistar rats were isolated, and the acute effects of an antagonist (NPS2390), agonists (putrescine and gadolinium), or of downregulation of the CaR by siRNA on cell shortening were recorded in a cell-edge-detection system. In addition, experiments were performed on muscle stripes and Langendorff preparations. Mechanistic insights were taken from calcium transients of beating fura-2 AM-loaded cardiomyocytes and western blots. Isolated ventricular cardiomyocytes constitutively express CaR. The expression in the atria is less pronounced. Acute inhibition of CaR reduced basal cell shortening of ventricular myocytes at nearly physiological levels of extracellular calcium. Inhibition of CaR strongly reduced contractility of ventricular muscle stripes but not of atria. Activation of CaR by putrescine and gadolinium influences the contractile responsiveness of isolated cardiomyocytes. Increased calcium mobilization from the sarcoplasmic reticulum via an IP3-dependent mechanism was responsible for amplified systolic calcium transients and a subsequent improvement in cell shortening. Alongside with these effects, activation of CaR increased relaxation velocity of the cells. In conclusion, ventricular CaR expression affects contractile parameters of ventricular heart muscle cells and modifies electromechanical coupling of cardiomyocytes. PMID:24687204

  20. Quantitative FDG-uptake by positron emission tomography in progressive hypertrophy of rat hearts in vivo

    International Nuclear Information System (INIS)

    Quantitative myocardial fluorodeoxyglucose positron emission tomography (FDG-PET) for assessing glucose uptake in vivo is reliable in normal rat heart. The objective of this study was to assess the applicability of myocardial FDG-PET on multiple occasions in the longitudinal disease process of progressive hypertrophy of rat heart. Six salt-sensitive Dahl rats (Dahl-S) developing progressive hypertrophy with subsequent dilated cardiomyopathy were compared with salt-resistant Dahl rats (controls). FDG-PET was applied twice at early stage (ES: 14-18 weeks) and at late stage (LS: 22-26 weeks) of hypertrophy. Standardized uptake value (SUV) was calculated for comparing between different animal weights and different injection dosages of FDG. For validating the quantitative study, radioactivity of a total of 36 tissue samples was compared with the corresponding PET values. The left ventricular mass in Dahl-S increased by 17% at ES and by 25% at LS. The SUV in Dahl-S was 95% of controls at ES and reduced to 62% at LS (P=0.023). The heart function started to deteriorate after LS. Linear regression analysis showed a good correlation between the radioactivity of tissue samples and PET values (Y=1.20 X, P2=0.979). Small animal PET studies on longitudinal multiple occasions in vivo were feasible and useful for the repeating assessment of glucose uptake. The reduction of glucose uptake in progressive hypertrophy of heart over time may precede its progression tot over time may precede its progression to heart failure. (author)

  1. Regional left ventricular diastolic function in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    To estimate regional left ventricular (LV) diastolic filling patterns in hypertrophic cardiomyopathy (HCM), a computer-assisted method by applying 'sector analysis' to ECG forward and reverse gated radionuclide ventriculography was developed. Fourteen patients with HCM (four with localized septal hypertrophy, seven with apical hypertrophy and three with septal and apical hypertrophy according to echocardiography) were observed at rest. After establishing serial 20 msec imaged frames, the LV region of interest was subdivided into eight sectors radiating from the geometric center. A time-activity curve was generated for each sector and was fitted by third-order harmonics of the Fourier series. From each fitted curve, the regional peak filling rate (rPFR) and the time to rPFR (rTPFR) in the forward gating method and regional atrial contribution to filling (rAC/FV) in the reverse gating method were calculated. The coefficient of variance of rTPFR was used as an index of LV diastolic asynchrony. In HCM, a prominent delay of rTPFR was observed in the hypertrophied regions. The coefficient of variance of rTPFR correlated inversely with global LVPFR (r=-0.62, p<0.05), indicating that diastolic asynchrony is one of the determinants of the LV early filling rate. Regional AC/FV was augmented in the hypertrophied regions, indicating the important role of atrial systolic LV filling for slowed early filling. Thus, this new method provides valuable information concerning regional dialuable information concerning regional diastolic LV wall mechanics in HCM. (author)

  2. Tamponade caused by cardiac lipomatous hypertrophy.

    OpenAIRE

    Myerson, Sg; Roberts, R.; Moat, N.; Pennell, Dj

    2004-01-01

    Cardiac lipomatous hypertrophy is an unusual disorder that typically affects the interatrial septum. We report a case in which large subpericardial deposits of fat were initially mistaken for a pericardial effusion and the subsequent clinical picture resembled tamponade. The patient improved following a pericardiectomy.

  3. Right ventricular obstructive hypertrophic cardiomyopathy in primary myo-adenylate deaminase deficiency.

    Science.gov (United States)

    de Gregorio, C; Morabito, G; Musumeci, O; Donato, R; Toscano, A

    2011-06-01

    MyoAdenylate Deaminase Deficiency (MADD) is a relatively common metabolic disorder of the skeletal muscle. Patients with MADD usually show an impaired bioenergetic production and a clinical spectrum with either exercise-induced muscle pain, fatigue and/or rhabdomyolysis. Left ventricular hypertrophy as well as other types of cardiac involvement have been reported in patients with primary MADD. We describe herein a case of a 61-year-old woman with biochemical and genetic evidence of Myo-Adenylate Deaminase deficiency, in whom we found a right ventricular hypertrophic cardiomyopathy leading to severe outflow tract dynamic obstruction. PMID:21842595

  4. Left ventricular diastolic function in valvular aortic stenosis after aortic valve replacement

    Directory of Open Access Journals (Sweden)

    Risti?-An?elkov An?elka

    2002-01-01

    Full Text Available In adults with significant sympthomatic aortic valve stenosis, aortic valve replacement is therapy of choice. Replacement of the diseased aortic valve with a prosthetic valve yields relief of left ventricular outflow obstruction. Myocardial remodeling with regression of mass transpires as the heart adapts to the new level of after load. In patients with moderate left ventricular hypertrophy improvement in diastolic function during the first year after aortic valve replacement is visible, while in patients with extreme myocardial hypertrophic changes it was slower.

  5. P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure

    Science.gov (United States)

    Yang, Ronghua; Beqiri, Dardan; Shen, Jian-Bing; Redden, John M.; Dodge-Kafka, Kimberly; Jacobson, Kenneth A.; Liang, Bruce T.

    2014-01-01

    We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na+) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF. PMID:25750695

  6. Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Brette, F.; Nelson, A.; Pearce, C.; Qaiser, A.; Christé, G.; Orchard, C.

    2008-01-01

    Ro?. 96, - (2008), s. 244-257. ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * transverse-axial tubular system * tubular membrane area * tubular membrane capacitance Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  7. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle.

    Czech Academy of Sciences Publication Activity Database

    Dealmeida, A.; McQuinn, T. C.; Sedmera, David

    2007-01-01

    Ro?. 100, - (2007), s. 1363-1370. ISSN 0009-7330 Institutional research plan: CEZ:AV0Z50450515 Keywords : chick embryo * hemodynamics * fetal surgery * hypoplastic left heart syndrome Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 9.721, year: 2007

  8. The functional role of cardiac T-tubules in a model of rat ventricular myocytes.

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Christé, G.

    2006-01-01

    Ro?. 364, ?. 1842 (2006), s. 1187-1206. ISSN 1364-503X Institutional research plan: CEZ:AV0Z20760514 Keywords : accumulation-depletion of ions * transverse tubule * heart Subject RIV: BO - Biophysics Impact factor: 2.282, year: 2006

  9. Infarto del ventrículo derecho Right ventricular infarction

    Directory of Open Access Journals (Sweden)

    Alberto Barón C

    Full Text Available Por lo general, el infarto del ventrículo derecho se asocia con infarto de la pared inferior del ventrículo izquierdo. La enfermedad pulmonar obstructiva crónica y la hipertrofia del ventrículo derecho, son factores que lo predisponen. Casi siempre ocurre como consecuencia de obstrucción proximal de la arteria coronaria derecha que conduce a disfunción sistólica y diastólica del ventrículo derecho. El volumen latido disminuye y el volumen diastólico y la presión de llenado del ventrículo derecho aumentan, con lo que se ocasiona hipotensión y congestión periférica. Se disminuyen el flujo sanguíneo pulmonar y el retorno venoso para el ventrículo izquierdo que puede llevar a estado de choque. Además, se pueden presentar complicaciones como bloqueo aurículo-ventricular, disfunción sinusal y aneurisma ventricular. El electrocardiograma muestra supradesnivel del ST en las derivaciones III, V1 a V3 y en V4R. El ecocardiograma muestra hipoquinesia o aquinesia de la pared libre del ventrículo derecho y hay dilatación de las cavidades derechas e insuficiencia tricúspide. El Doppler demuestra aumento en la duración de los intervalos de contracción y relajación isovolumétrica; el período eyectivo se acorta y el índice de desempeño miocárdico aumenta a valores anormales. El Doppler tisular es anormal por la disminución de la velocidad sistólica del anillo tricúspide. Una parte importante del tratamiento es optimizar el ritmo y la frecuencia cardiaca por lo que se debe evitar el uso de beta-bloqueadores; dependiendo de la severidad de la bradicardia se puede usar atropina, aminofilina o marcapasos transitorio, con la finalidad de asegurar una frecuencia adecuada. En caso de fibrilación auricular se pueden usar antiarrítmicos o cardioversión eléctrica. Se debe asegurar un adecuado volumen de llenado, para mantener la presión venosa central mayor de 15 mm Hg. El uso de vasodilatadores o diuréticos está contraindicado. Es importante recanalizar rápidamente la arteria obstruida mediante trombólisis o angioplastia. Si persisten signos de bajo gasto se debe usar inotrópico parenteral. Se puede usar un balón de contrapulsación aórtica o dispositivo de asistencia mecánica. Recientemente, se ha descrito el uso de óxido nítrico para reducir la resistencia vascular pulmonar y mejorar el gasto cardiaco.In general, right ventricular infarction is associated with left ventricular inferior wall infarction. Obstructive chronic pulmonary disease and right ventricular hypertrophy are predisposing factors. It usually occurs as a consequence of proximal obstruction of the right coronary artery, which leads to right systolic and diastolic ventricle dysfunction. Stroke volume is diminished and diastolic volume and right ventricular filling pressure increase, causing hypotension and peripheral congestion. Pulmonary blood flow and left ventricular venous return are diminished, which may lead to shock. Besides, complications such as atrioventricular block, sinus dysfunction and ventricular aneurysm may occur. The electrocardiogram shows ST elevation in leads III, V1 to V3 and in V4R. The echocardiogram shows right ventricular free wall hypokinesis or akinesis and there is right cavities dilation and tricuspid regurgitation. The Doppler shows an increment in the duration of isovolumetric contraction and relaxation intervals; the ejection period is shortened and the myocardial performance index increase to abnormal values. The tissue Doppler is abnormal because of the decrease of systolic velocity in the tricuspid annulus. The optimization of rhythm and heart rate is an important part of treatment, and by this reason, beta-blockers may be avoided; depending on the severity of bradycardia, atropine, aminophylline or transient pace-maker can be used in order to ensure an adequate heart rate. In case of atrial fibrillation, anti-arrhythmic drugs or electric cardioversion may be used. An adequate filling volume may be guaranteed for maintaining the central venous pressure over 15 mm Hg. The use o

  10. Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling.

    Science.gov (United States)

    Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya

    2003-12-23

    Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690

  11. Free and Bound Intracellular Calmodulin Measurements in Cardiac Myocytes

    OpenAIRE

    Wu, Xu; Bers, Donald M.

    2006-01-01

    Calmodulin (CaM) is a ubiquitous Ca2+ binding protein and Ca2+-CaM activates many cellular targets and functions. While much of CaM is thought to be protein bound, quantitative data in cardiac myocytes is lacking regarding CaM location, [CaM]free and CaM redistribution during changes in [Ca2+]i. Here, we demonstrated that in adult rabbit cardiac myocytes, CaM is highly concentrated at Z-lines (confirmed by Di-8-ANEPPS staining of transverse tubules) using three different approaches: immunocyt...

  12. INTRALIPID PREVENTS AND RESCUES FATAL PULMONARY ARTERIAL HYPERTENSION AND RIGHT VENTRICULAR FAILURE IN RATS

    OpenAIRE

    Umar, Soban; Nadadur, Rangarajan; Li, Jingyuan; Maltese, Federica; Partownavid, Parisa; Laarse, Arnoud van der; Eghbali, Mansoureh

    2011-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid®, a source of parenteral nutrition for patients, contains ?-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We therefore investigated the therapeutic potential of Intralipid® in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (...

  13. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... this procedure. And what are the EC change…ECG changes, the electrocardiographic changes that can be seen ... performing the surgical ventricular reconstruction. We may see ECG changes related to coronary artery disease, and those ...

  14. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... MD: Excellent. Another question is whether there's a risk of the development of a ventricular aneurysm after ...

  15. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... question is whether there's a risk of the development of a ventricular aneurysm after this procedure. And ... failure, and hopefully preventing patients from requiring mechanical device ... medical care. Montefiore-Einstein Heart Center, advanced care, visionary ...

  16. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... we see is the patient's ventricular function actually improves after this procedure, if done properly. 00:31: ... fact, have a low ejection infraction . It does improve pre-op…excuse me. It does improve postoperatively. ...

  17. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... 1 of 15 SURGICAL VENTRICULAR RECONSTRUCTION MONTEFIORE-EINSTEIN HEART CENTER NEW YORK CITY, NEW YORK February 13, ... 00:09 NARRATOR: Welcome to the Montefiore-Einstein Heart Center in New York City. In just moments, ...

  18. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... ventricular reconstruction by delineating the area of scar, putting a patch in and over-sewing the wall ... sense as to how much force you're putting to pass the needles. And that's because this ...

  19. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... you require an intraaortic balloon pump in the management of these patients. Do you want to answer ... because it can, in fact, improve the patient's quality of life, due to the improvement in ventricular ...

  20. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... that question, they are both good procedures. The gold standard therapy for heart failure is, in fact, ... to surgical ventricular reconstruction would add to the recovery period. And what we've found is that ...

  1. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... to surgical ventricular reconstruction would add to the recovery period. And what we've found is that ... to learn more. Just click on the "Request Information" button on your webcast screen and open the ...

  2. Surgical Ventricular Reconstruction

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    Full Text Available ... temporarily pace the heart during the immediate postoperative period. This is the vent that went into the ... surgical ventricular reconstruction would add to the recovery period. And what we've found is that not ...

  3. Surgical Ventricular Reconstruction

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    Full Text Available ... ventricual…left ventricular closure. And, that's a watertight seal. This really rarely bleeds. We've become so ... grade medical glue over the top to just seal some of the suture line. But you can ...

  4. Surgical Ventricular Reconstruction

    Medline Plus

    Full Text Available ... of the procedures that we perform are high risk mitral valve surgery. Previously, rather than the Dor ... MD: Excellent. Another question is whether there's a risk of the development of a ventricular aneurysm after ...

  5. Surgical Ventricular Reconstruction

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    Full Text Available ... in New York City. In just moments, you'll see an expert discussion concerning a surgical ventricular ... the operating room. And as we do, we'll begin to evolve our thinking and be at ...

  6. NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.

    Science.gov (United States)

    Gan, C T; McCann, G P; Marcus, J T; van Wolferen, S A; Twisk, J W; Boonstra, A; Postmus, P E; Vonk-Noordegraaf, A

    2006-12-01

    The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function. PMID:16971413

  7. Diabetes, gender, and left ventricular structure in African-Americans: the atherosclerosis risk in communities study

    Directory of Open Access Journals (Sweden)

    Liebson Philip R

    2006-11-01

    Full Text Available Abstract Background Cardiovascular risk associated with diabetes may be partially attributed to left ventricular structural abnormalities. However, the relations between left ventricular structure and diabetes have not been extensively studied in African-Americans. Methods We studied 514 male and 965 female African-Americans 51 to 70 years old, in whom echocardiographic left ventricular mass measurements were collected for the ARIC Study. In these, we investigated the independent association of diabetes with left ventricular structural abnormalities. Results Diabetes, hypertension and obesity prevalences were 22%, 57% and 45%, respectively. Unindexed left ventricular mass was higher with diabetes in both men (238.3 ± 79.4 g vs. 213.7 ± 58.6 g; p Conclusion In African-Americans, diabetes is associated with left ventricular hypertrophy and, with different patterns of left ventricular structural abnormalities between genders. Attenuation seen in adjusted associations suggests that the higher frequency of structural abnormalities seen in diabetes may be due to factors other than hyperglycemia.

  8. Thioredoxin and Ventricular Remodeling

    OpenAIRE

    Ago, Tetsuro; Sadoshima, Junichi

    2006-01-01

    Increasing bodies of evidence indicate that reactive oxygen species (ROS) produced by mitochondria and other sources play an essential role in mediating ventricular remodeling after myocardial infarction and the development of heart failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment of cells and inhibiting ventricular remodeling in the heart. Thioredoxin not only functions as a major antioxidant in the heart but also interacts with important signaling molecules an...

  9. Left ventricular apical diseases

    OpenAIRE

    Cisneros, Silvia; Duarte, Ricardo; Fernandez-perez, Gabriel C.; Castellon, Daniel; Calatayud, Julia; Lecumberri, In?igo; Larrazabal, Eneritz; Ruiz, Berta Irene

    2011-01-01

    There are many disorders that may involve the left ventricular (LV) apex; however, they are sometimes difficult to differentiate. In this setting cardiac imaging methods can provide the clue to obtaining the diagnosis. The purpose of this review is to illustrate the spectrum of diseases that most frequently affect the apex of the LV including Tako-Tsubo cardiomyopathy, LV aneurysms and pseudoaneurysms, apical diverticula, apical ventricular remodelling, apical hypertrophic cardiomyopathy, LV ...

  10. Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    SANDOR GYÖRKE

    2004-01-01

    Full Text Available Calsequestrin (CASQ2 is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR. Mutations in the cardiac calsequestrin gene (CASQ2 have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca2+ in cardiac muscle. CASQ2 serves as a reservoir for Ca2+ that is readily accessible for Ca2+-induced Ca2+ release (CICR and also as an active Ca2+ buffer that modulates the local luminal Ca-dependent closure of the SR Ca2+ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca2+ stores. Abnormal restitution of the Ca2+ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

  11. Verrucotoxin inhibits KATP channels in cardiac myocytes through a muscarinic M3 receptor-PKC pathway.

    Science.gov (United States)

    Wang, Jian-Wu; Yazawa, Kazuto; Hao, Li-Ying; Onoue, Yoshio; Kameyama, Masaki

    2007-06-01

    Verrucotoxin is the major component of venom from the stonefish (Synanceia verrucosa). Stings from the dorsal spines of the stonefish produce intensive pain, convulsions, hypotension, paralysis, respiratory weakness and collapse of the cardiovascular system, occasionally leading to death. It has been reported that verrucotoxin might modulate ATP-sensitive K+ (KATP) current in frog atrial fibers. However, the mechanism by which verrucotoxin acts on KATP current remains unclear. In this study, we examined whether verrucotoxin inhibited KATP current in guinea pig ventricular myocytes, using the patch clamp method. Verrucotoxin suppressed KATP current induced by pinacidil (KATP channel opener) in a concentration-dependent manner, with a half maximum concentration of 16.3 microg/ml. The effect of verrucotoxin on KATP current was suppressed by atropine (1 microM), a muscarinic receptor antagonist, or by 4-diphenylacetoxy-N-methylpiperidine (100 nM), a muscarinic M3 receptor antagonist. Furthermore, the effect of verrucotoxin on KATP current was attenuated by the protein kinase C (PKC) inhibitor chelerythrine (10 microM) and calphostin C (10 microM), yet not by the cAMP-dependent protein kinase (PKA) inhibitor H-89 (0.5 microM). These results suggest that verrucotoxin inhibits KATP current through the muscarinic M3 receptor-PKC pathway. These findings enhance our understanding of the toxic effects of verrucotoxin from the stonefish. PMID:17362922

  12. Dyad content is reduced in cardiac myocytes of mice with impaired calmodulin regulation of RyR2.

    Science.gov (United States)

    Lavorato, Manuela; Huang, Tai-Qin; Iyer, Venkat Ramesh; Perni, Stefano; Meissner, Gerhard; Franzini-Armstrong, Clara

    2015-04-01

    In cardiac muscle, calmodulin (CaM) regulates the activity of several membrane proteins involved in Ca(2+) homeostasis (CaV1.2; RyR2, SERCA2, PMCA). Three engineered amino acid substitutions in the CaM binding site of the cardiac ryanodine receptor (RyR2) in mice (Ryr2 (ADA/ADA) ) strongly affect cardiac function, with impaired CaM inhibition of RyR2, reduced SR Ca(2+) sequestration, and early cardiac hypertrophy and death (Yamaguchi et al., J Clin Invest 117:1344-1353, 2007). We have examined the ultrastructure and RyR2 immunolocalization in WT and Ryr2 (ADA/ADA) hearts at ~10 days after birth. The myocytes show only minor evidence of structural damage: some increase in intermyofibrillar space, with occasional areas of irregular SR disposition and an increase in frequency of smaller myofibrils, despite an increase of about 15 % in average myocyte cross sectional area. Z line streaming, a sign of myofibrillar stress, is limited and fairly rare. Immunolabeling with an anti-RyR2 antibody shows that RyR-positive foci located at the level of the Z lines are less frequent in mutant hearts. A dramatic decrease in the frequency and size of dyads, accompanied by a decrease in occupancy of the gap by RyR2, but without obvious alterations in location and general structure is a notable ultrastructural feature. The data suggest that the uneven distribution of dyads or calcium release sites within the cells resulting from an overall reduction in RyR2 content may contribute to the poor cardiac performance and early death of Ryr2 (ADA/ADA) mice. An unusual fragmentation of mitochondria, perhaps related to imbalances in free cytoplasmic calcium levels, accompanies these changes. PMID:25694159

  13. Heat stress inhibits skeletal muscle hypertrophy

    OpenAIRE

    Frier, Bruce C.; Locke, Marius

    2007-01-01

    Heat shock proteins (Hsps) are molecular chaperones that aid in protein synthesis and trafficking and have been shown to protect cells/tissues from various protein damaging stressors. To determine the extent to which a single heat stress and the concurrent accumulation of Hsps influences the early events of skeletal muscle hypertrophy, Sprague-Dawley rats were heat stressed (42°C, 15 minutes) 24 hours prior to overloading 1 plantaris muscle by surgical removal of the gastrocnemius muscle. The...

  14. Neuronal Hypertrophy in Asymptomatic Alzheimer Disease

    Science.gov (United States)

    Iacono, Diego; O’Brien, Richard; Resnick, Susan M.; Zonderman, Alan B.; Pletnikova, Olga; Rudow, Gay; An, Yang; West, Mark J.; Crain, Barbara; Troncoso, Juan C.

    2008-01-01

    The pathologic changes of Alzheimer disease (AD) evolve very gradually over decades before the disease becomes clinically manifest. Thus, it is not uncommon to find substantial numbers of A? plaques and neurofibrillary tangles in autopsy brains of older subjects with documented normal cognition, a state that we define as asymptomatic AD (ASYMAD). The goal of this study is to understand the morphometric substrate of ASYMAD subjects compared with mild cognitive impairment and definite AD cases. We used designed-based stereology to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in 4 cerebral regions: anterior cingulate gyrus, posterior cingulate gyrus, primary visual cortex, and CA1 of hippocampus. We examined and compared autopsy brains from 4 groups (n = 15 each) of participants in the Baltimore Longitudinal Study of Aging: ASYMAD, mild cognitive impairment, AD, and age-matched controls. We found significant hypertrophy of the neuronal cell bodies, nuclei, and nucleoli of CA1 of hippocampus and anterior cingulate gyrus neurons in ASYMAD subjects compared with control and mild cognitive impairment cases. In the posterior cingulate gyrus and primary visual cortex, the hypertrophy was limited to the nuclei and nucleoli. The hypertrophy of cortical neurons and their nuclei and nucleoli in ASYMAD may represent an early reaction to the presence of neurotoxic A? or tau, or a compensatory mechanism that prevents the progression of the disease into dementia. PMID:18520776

  15. Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

    Science.gov (United States)

    Dalpiaz, P. L. M.; Lamas, A. Z.; Caliman, I. F.; Ribeiro, R. F.; Abreu, G. R.; Moyses, M. R.; Andrade, T. U.; Gouvea, S. A.; Alves, M. F.; Carmona, A. K.; Bissoli, N. S.

    2015-01-01

    Background There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). Methodology / Principal Findings Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. Conclusion Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components. PMID:26010093

  16. Restrictive and hypertrophic cardiomyopathies in Noonan syndrome: the overlap syndromes.

    OpenAIRE

    Wilmshurst, P. T.; Katritsis, D.

    1996-01-01

    A woman with Noonan syndrome had clinical and haemodynamic features of restrictive cardiomyopathy. There was no ventricular hypertrophy on echocardiography but myocardial biopsies showed myocyte hypertrophy without pathological disarray. This case illustrates the overlap of the cardiac phenotypes of Noonan syndrome, restrictive cardiomyopathy, and hypertrophic cardiomyopathy.

  17. Left ventricular function in right ventricular overload

    International Nuclear Information System (INIS)

    This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more seveft ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

  18. Fibulin-2 deficiency attenuates angiotensin II-induced cardiac hypertrophy by reducing transforming growth factor-? signalling.

    Science.gov (United States)

    Zhang, Hangxiang; Wu, Jing; Dong, Hailong; Khan, Shaukat A; Chu, Mon-Li; Tsuda, Takeshi

    2014-02-01

    AngII (angiotensin II) is a potent neurohormone responsible for cardiac hypertrophy, in which TGF (transforming growth factor)-? serves as a principal downstream mediator. We recently found that ablation of fibulin-2 in mice attenuated TGF-? signalling, protected mice against progressive ventricular dysfunction, and significantly reduced the mortality after experimental MI (myocardial infarction). In the present study, we investigated the role of fibulin-2 in AngII-induced TGF-? signalling and subsequent cardiac hypertrophy. We performed chronic subcutaneous infusion of AngII in fibulin-2 null (Fbln2-/-), heterozygous (Fbln2+/-) and WT (wild-type) mice by a mini-osmotic pump. After 4 weeks of subpressor dosage of AngII infusion (0.2 ?g/kg of body weight per min), WT mice developed significant hypertrophy, whereas the Fbln2-/- showed no response. In WT, AngII treatment significantly up-regulated mRNAs for fibulin-2, ANP (atrial natriuretic peptide), TGF-?1, Col I (collagen type I), Col III (collagen type III), MMP (matrix metalloproteinase)-2 and MMP-9, and increased the phosphorylation of TGF-?-downstream signalling markers, Smad2, TAK1 (TGF-?-activated kinase 1) and p38 MAPK (mitogen-activated protein kinase), which were all unchanged in AngII-treated Fbln2-/- mice. The Fbln2+/- mice consistently displayed AngII-induced effects intermediate between WT and Fbln2-/-. Pressor dosage of AngII (2 mg/kg of body weight per min) induced significant fibrosis in WT but not in Fbln2-/- mice with comparable hypertension and hypertrophy in both groups. Isolated CFs (cardiac fibroblasts) were treated with AngII, in which direct AngII effects and TGF-?-mediated autocrine effects was observed in WT. The latter effects were totally abolished in Fbln2-/- cells, suggesting that fibulin-2 is essential for AngII-induced TGF-? activation. In conclusion our data indicate that fibulin-2 is essential for AngII-induced TGF-?-mediated cardiac hypertrophy via enhanced TGF-? activation and suggest that fibulin-2 is a potential therapeutic target to inhibit AngII-induced cardiac remodelling. PMID:23841699

  19. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in female than male non-hypertrophied hearts. Glucose oxidation was lower in female than male hearts and was unaffected by hypertrophy or ischemia. Consequently, non-oxidative catabolism of glucose after ischemia was lowest in male non-hypertrophied hearts and comparably elevated in hypertrophied hearts of both sexes. These differences in non-oxidative glucose catabolism were inversely related to post-ischemic functional recovery. Conclusion Gender does not significantly influence post-ischemic function of hypertrophied hearts, even though female sex is detrimental to post-ischemic function in non-hypertrophied hearts. Differences in glucose catabolism may contribute to hypertrophy-induced and gender-related differences in post-ischemic function.

  20. Right ventricular endomyocardial fibrosis.

    Science.gov (United States)

    Santra, Gouranga; Sinha, Pradip Kumar; Phaujdar, Sibaji; De, Dibyendu

    2012-03-01

    Endomyocardial fibrosis is a variety of restrictive cardiomyopathy, in which endocardium of one or both ventricles is thickened markedly with involvement of underlying myocardium. Partial obliteration of ventricular cavities by fibrous tissue and thrombus causes diastolic dysfunction with increased resistance to ventricular filling. Systolic function is well preserved till late stages. Biventricular or isolated left ventricular involvement is common. Isolated right ventricular involvement is relatively uncommon. Case reports on endomyocardial fibrosis have declined in literature. In India, endomyocardial fibrosis is mainly reported from Kerala. A case of right ventricular endomyocardial fibrosis from West Bengal is reported here. Isolated right sided endomyocardial fibrosis, massive right atrial enlargement, complete disorganization of tricuspid valve, massive pericardial effusion, normal absolute eosinophil count and its sporadic occurrence outside 15 degrees of the equatorial belt were interesting features in this case of endomyocardial fibrosis. X-ray features were typical of pericardial effusion masking underlying endomyocardial fibrosis. Endomyocardial fibrosis is a neglected research field. It needs more attention from biomedical researchers. PMID:22799123