Sample records for ventricular myocyte hypertrophy

  1. Left Ventricular Hypertrophy

    ... of left ventricular hypertrophy in hypertension. Accessed April 6, 2015. Podrid PJ. Left ventricular hypertrophy and arrhythmia. Accessed April 6, 2015. Chatterjee S, et ...

  2. Ventricular hypertrophy--physiological mechanisms.

    Vaughan Williams, E M


    Adult cardiac myocytes are incapable of mitosis. Dead cells are replaced by connective tissue so that after myocardial infarction (MI), function can only be restored by compensatory hypertrophy of the surviving myocardium. In physiological hypertrophy in response to exercise, high altitude, or mild hypertension, additional myoplasm expands cell diameter in an orderly fashion; Z-lines are in register and the normal ratio of volume densities of contractile elements, mitochondria, and capillaries is conserved. In hypertrophy induced by aortic or pulmonary artery banding or by experimental or congenital hypertension, the borderline between physiological and pathological hypertrophy may be crossed, causing disorganization of fibers and an unfavourable contractile element to capillary ratio. There was, therefore, a need for a graded model of hypertrophy, which involves simulating an altitude of 6,000 m at sea level by supplying rabbits with appropriate nitrogen/oxygen mixtures. In this environment, 50% right ventricular hypertrophy can be achieved without alteration of left ventricular weight or hematocrit. Longer exposures produced 100% right ventricular hypertrophy, with only moderate increases in hematocrit and left ventricular weight. It is well known that adrenergic stimulation causes cardiac hypertrophy, and it has been suggested that release of a trophic factor from sympathetic nerves, either noradrenaline or a protein, might be a necessary stimulus for growth. If so, long-term treatment of post-MI patients with beta-adrenergic blocking agents could inhibit a desirable compensatory hypertrophy of the surviving myocardium. In the above model it has been found, however, that neither beta-blockade nor chemical sympathectomy with guanethidine or 6-hydroxydopamine had any effect on the hypertrophy, nor did treatment with verapamil or nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    R.M. Saraiva


    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 response. 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.

  4. Hyperplasia of myocyte nuclei in long-term cardiac hypertrophy in rats.

    Olivetti, G; R. Ricci; Anversa, P.


    In contrast to observations made in the human heart, hyperplasia of myocyte nuclei has never been demonstrated in experimental cardiac hypertrophy. To test the hypothesis that the duration of the mechanical load more than the magnitude of ventricular hypertrophy may be the inciting stimulus for myocyte nuclei hyperplasia, constriction of the pulmonary artery was produced in rats and the hearts were examined 6 mo later. A 76% increase in right ventricular weight was measured. This hypertrophic...

  5. Mitochondria and left ventricular hypertrophy

    Haiyan Zhu; Shiwen Wang


    @@ Introduction Left ventricular hypertrophy (LVH) is one of the vicious organ damages of essential hypertension.It contributes a lot to high mortality of essential hypertension due to sudden cardiac death,ventricular arrhythmia and heart failure.Many factors involve in the pathogenesis of hypertension-induced LVH including inherited variants as well as environmental factors.

  6. Cardiac Hypertrophy Involves both Myocyte Hypertrophy and Hyperplasia in Anemic Zebrafish

    Xiaojing Sun; Tiffany Hoage; Ping Bai; Yonghe Ding; Zhenyue Chen; Ruilin Zhang; Wei Huang; Ashad Jahangir; Barry Paw; Yi-Gang Li; Xiaolei Xu


    BACKGROUND: An adult zebrafish heart possesses a high capacity of regeneration. However, it has been unclear whether and how myocyte hyperplasia contributes to cardiac remodeling in response to biomechanical stress and whether myocyte hypertrophy exists in the zebrafish. To address these questions, we characterized the zebrafish mutant tr265/tr265, whose Band 3 mutation disrupts erythrocyte formation and results in anemia. Although Band 3 does not express and function in the heart, the chroni...

  7. Oxidative stress decreases microtubule growth and stability in ventricular myocytes

    Drum, BML; Yuan, C.; Li, L; Liu, Q.; Wordeman, L; Santana, LF


    © 2016 Elsevier Ltd.Microtubules (MTs) have many roles in ventricular myocytes, including structural stability, morphological integrity, and protein trafficking. However, despite their functional importance, dynamic MTs had never been visualized in living adult myocytes. Using adeno-associated viral vectors expressing the MT-associated protein plus end binding protein 3 (EB3) tagged with EGFP, we were able to perform live imaging and thus capture and quantify MT dynamics in ventricular myocyt...

  8. Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish.

    Xiaojing Sun

    Full Text Available BACKGROUND: An adult zebrafish heart possesses a high capacity of regeneration. However, it has been unclear whether and how myocyte hyperplasia contributes to cardiac remodeling in response to biomechanical stress and whether myocyte hypertrophy exists in the zebrafish. To address these questions, we characterized the zebrafish mutant tr265/tr265, whose Band 3 mutation disrupts erythrocyte formation and results in anemia. Although Band 3 does not express and function in the heart, the chronic anemia imposes a sequential biomechanical stress towards the heart. METHODOLOGY/PRINCIPAL FINDINGS: Hearts of the tr265/tr265 Danio rerio mutant become larger than those of the sibling by week 4 post fertilization and gradually exhibit characteristics of human cardiomyopathy, such as muscular disarray, re-activated fetal gene expression, and severe arrhythmia. At the cellular level, we found both increased individual cardiomyocyte size and increased myocyte proliferation can be detected in week 4 to week 12 tr265/tr265 fish. Interestingly, all tr265/tr265 fish that survive after week-12 have many more cardiomyocytes of smaller size than those in the sibling, suggesting that myocyte hyperplasia allows the long-term survival of these fish. We also show the cardiac hypertrophy process can be recapitulated in wild-type fish using the anemia-inducing drug phenylhydrazine (PHZ. CONCLUSIONS/SIGNIFICANCE: The anemia-induced cardiac hypertrophy models reported here are the first adult zebrafish cardiac hypertrophy models characterized. Unlike mammalian models, both cardiomyocyte hypertrophy and hyperplasia contribute to the cardiac remodeling process in these models, thus allowing the effects of cardiomyocyte hyperplasia on cardiac remodeling to be studied. However, since anemia can induce effects on the heart other than biomechanical, non-anemic zebrafish cardiac hypertrophy models shall be generated and characterized.

  9. Left ventricular hypertrophy: an initial response to myocardial injury.

    Francis, G S; McDonald, K M


    The prevailing wisdom generally has been that the failing heart hypertrophies in response to increased wall stress. The increase in myocardial mass observed in heart failure is therefore a relatively late compensatory event geared to normalize wall stress. Although this is undoubtedly true, especially for heart failure resulting from a large anterior myocardial infarction accompanied by rapid left ventricular expansion, it is possible that an important form of hypertrophy occurs much earlier as an initial response to myocardial injury. One can hypothesize that the initial response to injury is a nonspecific phenotypic alteration of the cardiac myocyte to one of growth and development. Such changes may be driven by both trophic and mechanical forces and may be important in altering the architecture of the myocardial cell and surrounding cardiac interstitium. Preliminary data from a variety of models support the concept that neuroendocrine activity is an important component in the ventricular remodeling process, and that pharmacologic interventions designed to block systemic and tissue neuroendocrine activity may prevent excessive cardiac enlargement and its ultimate consequences. Because this concept has important implications for preventive cardiology, the results of several prevention trials, including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), Studies of Left Ventricular Dysfunction (SOLVD), and Survival and Ventricular Enlargement (SAVE) are awaited eagerly.

  10. Left ventricular hypertrophy : virtuous intentions, malign consequences

    Pokharel, S; Sharma, UC; Pinto, YM


    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there ar

  11. Oxidative stress decreases microtubule growth and stability in ventricular myocytes.

    Drum, Benjamin M L; Yuan, Can; Li, Lei; Liu, Qinghang; Wordeman, Linda; Santana, L Fernando


    Microtubules (MTs) have many roles in ventricular myocytes, including structural stability, morphological integrity, and protein trafficking. However, despite their functional importance, dynamic MTs had never been visualized in living adult myocytes. Using adeno-associated viral vectors expressing the MT-associated protein plus end binding protein 3 (EB3) tagged with EGFP, we were able to perform live imaging and thus capture and quantify MT dynamics in ventricular myocytes in real time under physiological conditions. Super-resolution nanoscopy revealed that EB1 associated in puncta along the length of MTs in ventricular myocytes. The vast (~80%) majority of MTs grew perpendicular to T-tubules at a rate of 0.06μm∗s(-1) and growth was preferentially (82%) confined to a single sarcomere. Microtubule catastrophe rate was lower near the Z-line than M-line. Hydrogen peroxide increased the rate of catastrophe of MTs ~7-fold, suggesting that oxidative stress destabilizes these structures in ventricular myocytes. We also quantified MT dynamics after myocardial infarction (MI), a pathological condition associated with increased production of reactive oxygen species (ROS). Our data indicate that the catastrophe rate of MTs increases following MI. This contributed to decreased transient outward K(+) currents by decreasing the surface expression of Kv4.2 and Kv4.3 channels after MI. On the basis of these data, we conclude that, under physiological conditions, MT growth is directionally biased and that increased ROS production during MI disrupts MT dynamics, decreasing K(+) channel trafficking.

  12. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

    Lai-jing SONG; Guan-lei WANG; Jie LIU; Qin-ying QIU; Jing-hua OU; Yong-yuan GUAN


    Aim:To examine how the sarcoplasmic reticulum (SR) Ca2+ content changes and the underlying mechanism in L-thyroxin-induced cardiac hypertrophy. Methods:Echocardiography was used to confirm the establishment of the cardiac hypertro-phy model. The confocal microscopy and fluorescent indicator Fluo-3 was ap-plied to examine the intracellular Ca2+ concentration ([Ca2+]I), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results:L-thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine-induced Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]I increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue. Conclusion:The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.

  13. Isorhamnetin protects rat ventricular myocytes from ischemia and reperfusion injury.

    Zhang, Najuan; Pei, Fei; Wei, Huaying; Zhang, Tongtong; Yang, Chao; Ma, Gang; Yang, Chunlei


    Ischemia/reperfusion (I/R) has been known to cause damages to ventricular myocytes. Isorhamnetin, one member of flavonoid compounds, has cardioprotective effect, the effect that suggests a possible treatment for I/R damages. In the present investigation, we found that isorhamnetin could significantly promote the viability of neonatal rat ventricular myocytes that were exposed to ischemia/reperfusion (I/R) in vitro. Ventricular myocytes were obtained from neonatal SD rats, and then were divided randomly into three groups, namely I/R-/isor-, I/R+/isor- and I/R+/isor+ group. Before the whole experiment, the most appropriate concentration of isorhamnetin (4 μM) was determined by MTT assay. Our results showed that isorhamnetin could alleviate the damages of I/R to ventricular myocytes through inhibiting lactate dehydrogenase (LDH) activity, and repressing apoptosis. Compared with the counterpart of the I/R+/isor- group, LDH activity in the isorhamnetin-treated group weakened, halving from 24.1 ± 2.3 to 11.4 ± 1.2U/L. Additionally, flow cytometry showed the apparently increased apoptosis rate induced by I/R, the result that was further confirmed by transmission electron microscope. Administration of isorhamnetin, however, assuaged the apoptosis induced by I/R. Corresponding to the reduced apoptosis rate in the I/R+/isor+ group, western blotting assay showed increased amount of Bcl-2 and p53, decreased amount of Bax, and nuclear accumulation of NF-κB/p65.

  14. Transgenic overexpression of Hdac3 in the heart produces increased postnatal cardiac myocyte proliferation but does not induce hypertrophy.

    Trivedi, Chinmay M; Lu, Min Min; Wang, Qiaohong; Epstein, Jonathan A


    Class I and II histone deacetylases (HDACs) play vital roles in regulating cardiac development, morphogenesis, and hypertrophic responses. Although the roles of Hdac1 and Hdac2, class I HDACs, in cardiac hyperplasia, growth, and hypertrophic responsiveness have been reported, the role in the heart of Hdac3, another class I HDAC, has been less well explored. Here we report that myocyte-specific overexpression of Hdac3 in mice results in cardiac abnormalities at birth. Hdac3 overexpression produces thickening of ventricular myocardium, especially the interventricular septum, and reduction of both ventricular cavities in newborn hearts. Our data suggest that increased thickness of myocardium in Hdac3-transgenic (Hdac3-Tg) mice is due to increased cardiomyocyte hyperplasia without hypertrophy. Hdac3 overexpression inhibits several cyclin-dependent kinase inhibitors, including Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, and Cdkn2c. Hdac3-Tg mice did not develop cardiac hypertrophy at 3 months of age, unlike previously reported Hdac2-Tg mice. Further, Hdac3 overexpression did not augment isoproterenol-induced cardiac hypertrophy when compared with wild-type littermates. These findings identify Hdac3 as a novel regulator of cardiac myocyte proliferation during cardiac development.

  15. Effects of Angiotensin Ⅱ on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

    Jun Yang; Wei Wu


    To study the effects of angiotensin Ⅱ,as a mediator of cardiac hypertrophy,on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy.Methods Cardiomyocytes were isolated from newborn SD rats.Angiotensin Ⅱ was added into the media to induce myocyte hypertrophy.Cultures were exposed to 10 ~6 mol/L angiotensin Ⅱ for 72 h,Cx43 expression was characterized by RT-PCR and Immunofluorescence methods.Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin Ⅱ.RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin Ⅱ for 72 h.The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle.Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin Ⅱ ( 1.0 × 10-9 ~ 1.0 × 10-6mol/L),resulting in significantly decreased Cx43 expression.Conclusions Angiotensin Ⅱ leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis.Signal transduction pathways activated by angiotensin Ⅱ under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.

  16. Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

    Amanda L. Vega


    sarcoplasmic reticulum (SR and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+] during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

  17. A unified theory of calcium alternans in ventricular myocytes

    Qu, Zhilin; Liu, Michael B.; Nivala, Michael


    Intracellular calcium (Ca2+) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca2+ cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca2+ alternans. Two mechanisms of Ca2+ alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca2+ release and uptake, and the other on refractoriness and other properties of Ca2+ sparks. Each of the two mechanisms can partially explain the experimental observations, but both have their inconsistencies with the experimental results. Here we developed an iterated map model that is composed of two coupled iterated maps, which unifies the two mechanisms into a single cohesive mathematical framework. The unified theory can consistently explain the seemingly contradictory experimental observations and shows that the two mechanisms work synergistically to promote Ca2+ alternans. Predictions of the theory were examined in a physiologically-detailed spatial Ca2+ cycling model of ventricular myocytes. PMID:27762397

  18. Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats

    CHEN Hong-juan; YAO Lei; CHEN Tu-gang; YU Min; WANG Li-hong; CHEN Jun-zhu


    Background Connexin43 (Cx43) is the predominant gap junction protein in heart and is involved in the control of cell-to-cell communication to modulate the contractility and the electrical coupling of cardiac myocytes. Left ventricular(LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies have demonstrated that statins reduced cardiac hypertrophy. However, it is unknown whether statins can affect Cx43 expression in hypertrophied left ventricular myocardium. This study was designed to assess the effects of atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive rats (SHR).Methods Nine-week old SHRs were randomly divided into two groups. Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR-A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received atorvastatin or vehicle for 8 weeks were used as controls. At the end of the experiment, we investigated LV hypertrophy and the expression of Cx43 in LV myocardium in four groups. Cx43 expression was investigated by the methods of Western blotting, immunohistochemistry, and transmission electron microscope. LV hypertrophy was accessed by pathological analysis and plasma brain natriuretic peptide (BNP) level.Results LV hypertrophy was prominent in untreated SHR. In SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was displaced from their usual locations to other sites at various distances away from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level was reduced in SHR-A, and the distribution of Cx43 gap junction became much regular and confined to intercalated disk. Statins also prevented LV hypertrophy in SHR.Conclusions These results provide novel in vivo evidence for the key role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti-hypertrophic effect of statins. Atorvastatin treatment may have beneficial effects on LV hypertrophy in spontaneously hypertensive

  19. Responses of hypertrophied myocytes to reactive species: implications for glycolysis and electrophile metabolism.

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


    During cardiac remodelling, 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 ischaemia or in the failing heart. For this, we measured energetics in control and PE (phenylephrine)-treated NRCMs (neonatal rat cardiomyocytes) under basal conditions and when stressed with HNE (4-hydroxynonenal). PE treatment caused hypertrophy as indicated by augmented atrial natriuretic peptide and increased cellular protein content. Hypertrophied myocytes demonstrated a 2.5-fold increase in ATP-linked oxygen consumption and a robust augmentation of oligomycin-stimulated glycolytic flux and lactate production. Hypertrophied myocytes displayed a protected phenotype that was resistant to HNE-induced cell death and a unique bioenergetic response characterized by a delayed and abrogated rate of oxygen consumption and a 2-fold increase in glycolysis upon HNE exposure. This augmentation of glycolytic flux was not due to increased glucose uptake, suggesting that electrophile stress results in utilization of intracellular glycogen stores to support the increased energy demand. Hypertrophied myocytes also had an increased propensity to oxidize HNE to 4-hydroxynonenoic acid and sustained less protein damage due to acute HNE insults. Inhibition of aldehyde dehydrogenase resulted in bioenergetic collapse when myocytes were challenged with HNE. The integration of electrophile metabolism with glycolytic and mitochondrial energy production appears to be important for maintaining myocyte homoeostasis under conditions of increased oxidative stress.


    符民桂; 张继峰; 许松; 庞永政; 刘乃奎; 唐朝枢


    Objective. The present study investigated the role of calcineurin in angiotensin II(AngII) induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H leucine incorporation; atrial natriuretic factor(ANF) Mrna level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13% ,57% (P< 0.05) and 228% (P< 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H leucine incorporation in AngII treated cardiomyocytes in a dose dependent manner. It was also found that CsA slightly reduced the Mrna level of ANF gene in AngII stimulated cardiomyocytes. Conclusion. During AngII induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII induced myocardial hypertrophy of rats.

  1. Arterial baroreflex function and left ventricular hypertrophy

    MIAO Chao-Yu; SU Ding-Feng


    It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.

  2. Salt and left ventricular hypertrophy: what are the links?

    Langenfeld, M R; Schmieder, R E


    Left ventricular hypertrophy is a frequent and prognostically unfavourable finding in patients with essential hypertension and has been found to be a predictor for the development of essential hypertension in normotensive subjects. Among various genetic, haemodynamic and humoral determinants, dietary salt intake has been demonstrated to influence left ventricular mass in hypertensive disease. Several cross-sectional studies have shown a close relation between dietary salt intake and parameters of left ventricular hypertrophy. Moreover, reduction of dietary sodium intake was associated with a decrease of left ventricular mass in a prospective study. The underlying mechanism of how salt intake modulates myocardial structure has not been explained yet. Three possible explanations are discussed: (1) sodium influences left ventricular mass via raised preload, (2) the sympathetic nervous system acts as a mediator, and (3) the renin-angiotensin-aldosterone system is the responsible link. Recent animal experiments and clinical studies suggest that the renin-angiotensin-aldosterone system may mediate both the cardiotrophic and the blood pressure raising effects of salt. However, not all individuals have a similar high susceptibility to blood pressure elevation develop left ventricular hypertrophy when exposed to high salt intake. We suggest that the underlying mechanism is a dysregulation of the renin-angiotensin-aldosterone system. Some individuals may have an impaired downregulation of angiotensin II synthesis when challenged with high salt intake. Accordingly, we found that relatively too high levels of angiotensin II in relation to urinary sodium excretion were associated with left ventricular hypertrophy in these individuals on high salt intake.

  3. CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.

    Tang, Fu-Cai; Wang, Hong-Yan; Ma, Ming-Ming; Guan, Tian-Wang; Pan, Long; Yao, Dun-Chen; Chen, Ya-Lan; Chen, Wei-Bei; Tu, Yong-Sheng; Fu, Xiao-Dong


    The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.

  4. Association of heart failure hospitalizations with combined electrocardiography and echocardiography criteria for left ventricular hypertrophy

    Gerdts, Eva; Okin, Peter M; Boman, Kurt;


    The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain.......The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain....

  5. Effect of Sodium Tanshinone Ⅱ A Sulfonate on Cardiac Myocyte Hypertrophy and Its Underlying Mechanism


    Objective:To investigate the effects of sodium tanshinone Ⅱ A sulfonate (STS) on the hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ) in primary cultured neonatal rat cardiac myocytes.Methods:The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) assay.As indexes for cardiocyte hypertrophy,cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation.The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction (RT-PCR).Results:STS could inhibit cardiocyte hypertrophy,increase the protein synthesis rate and enhance proto-oncogene c-los mRNA expression in cardiocytes induced by Ang Ⅱ (P<0.01),with an effect similar to that of Valsartan,the Ang Ⅱ receptor antagonist.Conclusion:STS can prevent the hypertrophy of cardiac myocytes induced by Ang Ⅱ,which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.

  6. Electrocardiographic criteria for left ventricular hypertrophy in children.

    Rijnbeek, P.R.; Herpen, G van; Kapusta, L.; Harkel, AD Ten; Witsenburg, M.; Kors, J.A.


    Previous studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete limits of norma

  7. Stimulation of isolated ventricular myocytes within an open architecture microarray.

    Klauke, Norbert; Smith, Godfrey L; Cooper, Jonathan M


    This paper is concerned with the physiological responses of single heart cells within microfluidic chambers, in response to stimulation by integrated microelectrodes. To enable these investigations, which included the measurement of action potential duration, intracellular Ca2+ and cell shortening, a series of microfluidic chambers (50 microm wide, 180 microm long, 400 microm high, 500 microm pitch) and connecting channels (200 microm wide, 5000 microm long, 50 microm high, 500 microm pitch) were replica-moulded into the silicone elastomer, polydimethylsiloxane (PDMS). The structures were formed against a master of posts and lines, photolithograhically patterned into the high aspect ratio photoresist SU-8. The chambers within the slab of PDMS were aligned against pairs of stimulating gold microelectrodes (50 microm long, 20 microm wide, 0.1-10 microm thick, 180 microm apart) patterned on a microscope coverslip base, thus defining cavities of approximately 4 nL volume. The assembly was filled with physiological saline and single isolated rabbit ventricular myocytes were introduced by micropipetting, thus creating limited volumes of saline above individual myocytes that could be varied between 4 nL and > or = 4 microL. The application of transient current pulses to the cells via the electrodes caused transient contractions with constant amplitude (recorded as changes in sarcomere length), confirming that excitation contraction coupling (EC coupling) remained functional in these limited volumes. Continuous monitoring of the intracellular Ca2+ (using calcium sensitive dyes) showed, that in the absence of bath perfusion, the amplitude of the transients remained constant for approximately 3 min in the 4-nL volume and approximately 20 min for the 4 microL volume. Beyond this time, the cells became unexcitable until the bath was renewed. The action potential duration (APD) was recorded at stimulation frequencies of 1 Hz and 0.5 Hz using potential sensitive dyes and was

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

    Palade Philip T


    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

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

    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)


    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, Phypertrophy 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.

  10. Effect of Transmurally Heterogeneous Myocyte Excitation-Contraction Coupling on Left Ventricular Electromechanics


    The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation-contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global hemodynamics. This...

  11. Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

    Berger, H J; Prasad, S K; Davidoff, A J; Pimental, D; Ellingsen, O; Marsh, J D; Smith, T W; Kelly, R A


    To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

  12. Study of transmembrane La3+ movement in rat ventricular myocytes by the patch-clamp technique


    We have studied transmembrane La3+ movement in rat ventricular myocytes for the first time by using the whole-cell patch-clamp recording mode. La3+ (0.01-5.0 mmol/L) could not bring out inward currents through the L-type calcium channel in rat ventricular myocytes, while it could enter the cells by the same way carried by 1μmol/L ionomycin. When the outward Na+ concentration gradient is formed, La3+ can enter the cells via Na-Ca exchange, and the exchange currentsincrease with the increase of external La3+ concentrations. But compared with Na-Ca exchange currents in the same concentration, the former is only 14%-38% of the latter. The patch-clamp experiment indicates that La3+ normally can not enter ventricular myocytes through L-type calcium channel, but it can enter the cells via Na-Ca exchange.

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

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


    Repeated administration of 3,4-methylenedioxymethamphetamine (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 alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-cysteine (NAC). The metabolites of MDMA, but not MDMA alone, significantly decreased contractility and impaired relaxation in myocytes stimulated at 1 Hz. These effects were prevented by NAC. Together, these data suggest that MDMA-induced oxidative stress in the left ventricle can be due, at least in part, to the metabolism of MDMA to redox active metabolites.

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

    Yang Zhen-Yu


    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ω-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 μmol/L to 100 μmol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 μmol/L to 1 μmol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, and its half-inhibited concentration was 5.3 μmol/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.

  15. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992-2014).

    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P


    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease.

  16. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992–2014)

    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P


    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease. PMID:27053572

  17. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

    Qiangzhe Zhang; Li Chen; Tian Tian; Xin Wang; Pu Li; Jurgen Hescheler; Guangju Ji; Yue Ma; Junjie Jiang; Pengcheng Han; Qi Yuan; Jing Zhang; Xiaoqian Zhang; Yanyan Xu; Henghua Cao; Qingzhang Meng


    Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs)are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, hut not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiologicai studies indicated that with 64.7 ± 0.88% (mean ± s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 ± 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial- and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin

  18. Second statement of the working group on electrocardiographic diagnosis of left ventricular hypertrophy

    Bacharova, Ljuba; Estes, E Harvey; Bang, Lia E


    The Working Group on Electrocardiographic Diagnosis of Left Ventricular Hypertrophy, appointed by the Editor of the Journal of Electrocardiology, presents the alternative conceptual model for the ECG diagnosis of left ventricular hypertrophy (LVH). It is stressed that ECG is a record of electrical...

  19. The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

    Yidong Wei


    Full Text Available Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb’s compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (INa, outward currents delayed rectifier outward K+ current (IK, slowly activating delayed rectifier outward K+ current (IKs, transient outward K+ current (Ito, and inward rectifier K+ current (IK1. Qiliqiangxin can decrease INa by 28.53%±5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2%±6.4% and 55.9%±5.5% summit current density of Ito. 10 and 50 mg/L Qiliqiangxin decreased IKs by 15.51%±4.03% and 21.6%±5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy.

  20. FAK-related nonkinase attenuates hypertrophy induced by angiotensin-Ⅱ in cultured neonatal rat cardiac myocytes

    Jin QIN; Zheng-xiang LIU


    Aim: To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms. Methods: A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-Ⅱ stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-κB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot. Results: Under the stimulation of angiotensin Ⅱ, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-κB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT. Conclusion: FRNK may inhibit angiotensin-Ⅱ-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-κB p65.

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

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


    systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n......In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial...... with larger left ventricular diameter and higher left ventricular mass index (both P ventricular hypertrophy was greater (84 vs. 64%; P



    Objective. To investigate the effects of coxsackievims B3 (CVB3) on ion channel currents in rat ventricular my-Methods. Rat hearts were isolated with collagenase to acquire single ventricular myocytes, L-type voltnge-depen-dent calcium channel( VDCC)current (Ica), Na + current (INa), outward potassium current (Iout), inwardly rectifying potassium current(IKI) were recorded using whole cell patch clamp techniques. Results. CVB3 infection increased Ica and Iout, while decreased IKI; but it had no obvious effect on INa. Conclusion. Tne effects of CVB3 on Ica、 Iout、 IKI may be one of the mechanisms of myocytes damage and the oc-currence of abnormal electroactivities induced by CVB3 infection.

  3. Effect of miR-29a inhibition on ventricular hypertrophy induced by pressure overload.

    Han, Wei; Han, Yancong; Liu, Xiaokun; Shang, Xiaoming


    To investigate whether inhibition of miR-29a functioning prevents the hypertension-induced ventricular hypertrophy and fibrosis. Patients diagnosed with hypertension and left ventricular hypertrophy were recruited for the study. Serum levels of miR-29a were determined by RT-PCR. Levels of serum matrix metalloproteinase-9 (MMP-9), collagen type I and III (PINP and PIIINP) were determined by double-antibody enzyme-linked immunosorbent assay. Mouse model of transverse aortic constriction (TAC) was established. 7 days after surgery, TAC mice were injected intraperitoneally with antagomir miR-29a or vehicle once a day for 3 days. After 4 weeks of surgery, animals were sacrificed and cross-sections of the hearts were stained and evaluated for hypertrophy and fibrosis. The expression of the protein markers of hypertrophy and fibrosis was determined by immunoblotting. The serum level of miR-29a in hypertensive patients with left ventricular hypertrophy was significantly higher than those in patients with hypertension alone (p hypertrophy of cardiomyocytes and the expression of ANP and β-MHC, the hypertrophy indices. Also, the ventricular fibrosis and expression of the marker proteins were blocked in antagomir treated mice. The inhibition of miR-29a was found to be effective in improving the ventricular remodeling and hypertrophy caused by pressure overload.

  4. Progressive development of pulmonary hypertension leading to right ventricular hypertrophy assessed by echocardiography in rats.

    Kato, Yosuke; Iwase, Mitsunori; Kanazawa, Hiroaki; Kawata, Natsuki; Yoshimori, Yukie; Hashimoto, Katsunori; Yokoi, Toyoharu; Noda, Akiko; Takagi, Kenzo; Koike, Yasuo; Nishizawa, Takao; Nishimura, Masahiko; Yokota, Mitsuhiro


    The present study aimed to evaluate the development of pulmonary hypertension by serial echocardiography, including measurements of pulmonary artery (PA) flow velocities, and correlate echocardiographic indices with pathological findings in rats administered monocrotaline (MCT). MCT (60 mg/kg body weight) or physiologic saline was administered to a total of 9 male Wistar rats at the age of 4 weeks (MCT group: n = 4, control group: n = 5, respectively). Echocardiography was performed serially until the age of 8 weeks. The ratio of right ventricular (RV) outflow tract dimensions to aortic dimensions increased progressively in the MCT group and became significantly greater than that of the control group after the age of 6 weeks. Peak PA velocity (Peak V) in the MCT group was significantly less than that of the control group at the ages of 7 and 8 weeks. The ratio of acceleration time to ejection time (AT/ET) in PA flow waveforms declined progressively and was significantly less than that of the control group after the age of 6 weeks. The ratio of RV weight to body weight (RVW/BW) in the MCT group was significantly greater than that of the control group. Both AT/ET ratio and Peak V were significantly inversely correlated with RVW/BW ratio. Furthermore, these echocardiographic findings were also significantly inversely correlated with the mean cross-sectional RV myocyte area. In conclusion, the progressive development of pulmonary hypertension leading to RV hypertrophy can be evaluated appropriately by echocardiography including PA flow Doppler indices in rats.

  5. An Experimental Model Using Cultured Cardiac Myocytes for a Study of the Generation of Premature Ventricular Contractions Under Ultrasound Exposure

    Kudo, Nobuki; Yamamoto, Masaya


    It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.

  6. Calcium release near L-type calcium channels promotes beat-to-beat variability in ventricular myocytes from the chronic AV block dog.

    Antoons, Gudrun; Johnson, Daniel M; Dries, Eef; Santiago, Demetrio J; Ozdemir, Semir; Lenaerts, Ilse; Beekman, Jet D M; Houtman, Marien J C; Sipido, Karin R; Vos, Marc A


    Beat-to-beat variability of ventricular repolarization (BVR) has been proposed as a strong predictor of Torsades de Pointes (TdP). BVR is also observed at the myocyte level, and a number of studies have shown the importance of calcium handling in influencing this parameter. The chronic AV block (CAVB) dog is a model of TdP arrhythmia in cardiac hypertrophy, and myocytes from these animals show extensive remodeling, including of Ca(2+) handling. This remodeling process also leads to increased BVR. We aimed to determine the role that (local) Ca(2+) handling plays in BVR. In isolated LV myocytes an exponential relationship was observed between BVR magnitude and action potential duration (APD) at baseline. Inhibition of Ca(2+) release from sarcoplasmic reticulum (SR) with thapsigargin resulted in a reduction of [Ca(2+)]i, and of both BVR and APD. Increasing ICaL in the presence of thapsigargin restored APD but BVR remained low. In contrast, increasing ICaL with preserved Ca(2+) release increased both APD and BVR. Inhibition of Ca(2+) release with caffeine, as with thapsigargin, reduced BVR despite maintained APD. Simultaneous inhibition of Na(+)/Ca(2+) exchange and ICaL decreased APD and BVR to similar degrees, whilst increasing diastolic Ca(2+). Buffering of Ca(2+) transients with BAPTA reduced BVR for a given APD to a greater extent than buffering with EGTA, suggesting subsarcolemmal Ca(2+) transients modulated BVR to a larger extent than the cytosolic Ca(2+) transient. In conclusion, BVR in hypertrophied dog myocytes, at any APD, is strongly dependent on SR Ca(2+) release, which may act through modulation of the l-type Ca(2+) current in a subsarcolemmal microdomain.

  7. Effects of Glucose on Transmembrane Ionic Current of Ventricular Myocytes in Guinea Pig

    AIJing; JIAOJun-dong; WANGHe; DUZhi-min; YANGBao-feng


    Aim To determine the effects of glucose oi1APD, IK1, IK, ICa-L of ventricular myocytes in guinea pigs. Methods Whole-cell patch-clamp technique was used to record the changed action potential ionic current induced by glucose of single cell in guinea pig ventricular myocytes, to compare the action of 0, 10 and 20 mmol·L-1 glucoses on transmembrane ionic current. Results (1) Compared with 10 mmol·L-1 glucose concentrations, 0 and 20 mmol·L-1 glucose both shortened APD of ventricular myocytes (P<0.05). (2) The inward components of IK1 density were maximal when the glucose concentration was at 10 mmol·L-1. Normalized 1-V relationships showed that both 0 and 20 mmol·L-1 glucose produced a left-shift of I-V curve. The reverse potential changed from-72.4 mV to-64.6 mV. (3) Compared with 10 mmol·L-1, both 0 and 20 mmol·L-1 glucose markedly increased the ICa-L amplitude and density. The ICa-L current density was (-8.0350.82) pA/pF (n=8) at a test potential of 10 mV when the glucose concentration was 10 mmol·L-1. But its current density decreased to (-5.45±0.67) pA/pF and (-6.50±0.56) pA/pF when glucose concentrations were 0 and 20 mmol·L-1, respectively. (4) The current densities of IK were (18.96±2.86) pA/pF, (8.66±1.87) pA/pF, and(15.32:1:3.12) pA/pF, at ±70mV for 0, 10 and 20 mmol·L-1 glucoses, respectively. Conclusion Glucose in different concentrations has different effects on APD, IK1, IK, and ICa-L of single ventricular myocyte in guinea pigs. There are similar actions of 0 and 20 mmol·L-1 glucoses on the transmembrane ionic current of ventricular myocytes in guinea pigs.

  8. Temporal evaluation of cardiac myocyte hypertrophy and hyperplasia in male rats secondary to chronic volume overload.

    Du, Yan; Plante, Eric; Janicki, Joseph S; Brower, Gregory L


    The temporal myocardial remodeling induced by chronic ventricular volume overload in male rats was examined. Specifically, left ventricular (LV) cardiomyocyte length and width, sarcomere length, and number of nuclei were measured in male rats (n = 8 to 17) at 1, 3, 5, 7, 21, 35, and 56 days after creation of an infrarenal aortocaval fistula. In contrast to previously published reports of progressive increases in cardiomyocyte length and cross-sectional area at 5 days post-fistula and beyond in female hearts, cardiomyocyte length and width did not increase significantly in males during the first 35 days of volume overload. Furthermore, a significant decrease in cardiomyocyte length relative to age-matched controls, together with a reduced number of sarcomeres per cell, was noted in male hearts at 5 days post-fistula. There was a concurrent increase in the percentage of mononucleated cardiomyocytes from 11.6% to 18% at 5 days post-fistula. These initial differences could not be attributed to cardiomyocyte proliferation, and treatment with a microtubule stabilizing agent prevented them from occurring. The subsequent significant increase in LV weight without corresponding increases in cardiomyocyte dimensions is indicative of hyperplasia. Thus, these findings indicate hyperplasia resulting from cytokinesis of cardiomyocytes is a key mechanism, independent of hypertrophy, that contributes to the significant increase in LV mass in male hearts subjected to chronic volume overload.

  9. Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

    Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L


    OBJECTIVE: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. METHODS: Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH...

  10. Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

    Sandager Petersen, Søren; Reinholdt Pedersen, Line; Pareek, Manan


    OBJECTIVE: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. METHODS: We tested cross-sectional associations...

  11. Left Ventricular Hypertrophy Evaluation in Obese Hypertensive Patients: Effect of Left Ventricular Mass Index Criteria

    Eduardo Cantoni Rosa


    Full Text Available PURPOSE: To evaluate left ventricular mass (LVM index in hypertensive and normotensive obese individuals. METHODS: Using M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA and for height² (LVM/h². The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI: or = 30kg/m². RESULTS: The BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height² provides significantly increased values for high BMI subgroups in normotensive and hypertensive populations. CONCLUSION: Left ventricular hypertrophy (LVH has been underestimated in the obese with the use of LVM/BSA because this index considers obesity as a physiological variable. Indexing by height² allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

  12. Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M


    We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).......We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH)....

  13. Asymmetric left ventricular hypertrophy associated with morbid obesity mimicking familial hypertrophic cardiomyopathy.

    Wong, Raymond Ching-Chiew; Tan, Kong Bing


    Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM.

  14. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog.

    LeGrice, I J; Smaill, B H; Chai, L Z; Edgar, S G; Gavin, J B; Hunter, P J


    We have studied the three-dimensional arrangement of ventricular muscle cells and the associated extracellular connective tissue matrix in dog hearts. Four hearts were potassium-arrested, excised, and perfusion-fixed at zero transmural pressure. Full-thickness segments were cut from the right and left ventricular walls at a series of precisely located sites. Morphology was visualized macroscopically and with scanning electron microscopy in 1) transmural planes of section and 2) planes tangential to the epicardial surface. The appearance of all specimens was consistent with an ordered laminar arrangement of myocytes with extensive cleavage planes between muscle layers. These planes ran radially from endocardium toward epicardium in transmural section and coincided with the local muscle fiber orientation in tangential section. Stereological techniques were used to quantify aspects of this organization. There was no consistent variation in the cellular organization of muscle layers (48.4 +/- 20.4 microns thick and 4 +/- 2 myocytes across) transmurally or in different ventricular regions (23 sites in 6 segments), but there was significant transmural variation in the coupling between adjacent layers. The number of branches between layers decreased twofold from subepicardium to midwall, whereas the length distribution of perimysial collagen fibers connecting muscle layers was greatest in the midwall. We conclude that ventricular myocardium is not a uniformly branching continuum but a laminar hierarchy in which it is possible to identify three axes of material symmetry at any point.

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

    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


    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 (1μM) 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 (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM 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.

  16. Left ventricular hypertrophy in children, adolescents and young adults with sickle cell anemia

    Gustavo Baptista de Almeida Faro


    Full Text Available OBJECTIVE: The aims of this study were to estimate the frequency of left ventricular hypertrophy and to identify variables associated with this condition in under 25-year-old patients with sickle cell anemia.METHODS: A cross-sectional study was performed of children, adolescents and young adults with sickle cell anemia submitted to a transthoracic Doppler echocardiography. The mass of the left ventricle was determined by the formula of Devereux et al. with correction for height, and the percentile curves of gender and age were applied. Individuals with rheumatic and congenital heart disease were excluded. The patients were divided into two groups according to the presence or absence of left ventricular hypertrophy and compared according to clinical, echocardiographic and laboratory variables.RESULTS: A total of 37.6% of the patients had left ventricular hypertrophy in this sample. There was no difference between the groups of patients with and without hypertrophy according to pathological history or clinical characteristics, except possibly for the use of hydroxyurea, more often used in the group without left ventricular hypertrophy. Patients with left ventricular hypertrophy presented larger left atria and lower hemoglobin and hematocrit levels, reticulocyte index and a higher albumin:creatinine ratio in urine.CONCLUSION: Left ventricular hypertrophy was observed in more than one-third of the young patients with sickle cell anemia with this finding being inversely correlated to the hemoglobin and hematocrit levels, and reticulocyte index and directly associated to a higher albumin/creatinine ratio. It is possible that hydroxyurea had had a protective effect on the development of left ventricular hypertrophy.


    V. N. Poptsov


    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. The Effect and Mechanism of Forsinopril on Ventricular Hypertrophy of SHR and Left Ventricular Pressure overloading Rat

    黄恺; 戴闺柱


    The effects and mechanism of long-term angiotensin converting enzyme inhibitor (ACEI)Forsinopril on left ventricular hypertrophy of spontaneous hypertension rat (SHR) and left ventricular pressure overloading rat were studied. The left ventricular index (left ventricle weight/body weight) was used to evaluate left ventricular hypertrophy and the in situ hybridization to investigate the TGF-β1 gene expression in left ventricle. The results showed that Forsinopril significantly decreased the left ventricular index of both SHR and left ventricle pressure overloading rat. Forsinopril reduced the integral photic density of TGF-β1 gene statement from 2. 836± 0. 314 to 1.91 ± 0. 217(P<0.01, n=8 ) of SHR rat and from 3. 071±0. 456 to 2. 37640. 379 (P<0.01, n=8) of left ventricular pressure overloading rat respectively. It was concluded that Forsinopril could prevent the occurrence of left ventricular hypertrophy and reduce the TGF-β1 gene expression in left ventricle of both SHR and left ventricular pressure overloading rat significantly.

  19. Gene Product Expression of Cyclin D2 and p16 During the Transition from Cardiac Myocyte Hyperplasia to Hypertrophy


    The current study was to investigate mRNA expression of cyclin D2 and p16 during the transition from cardiac myocyte hyperplasia to hypertrophy. Cultured cardiac myocytes (CM) and fibroblasts (FC) obtained from 1-day-old Sparague-Dawley rats were used in this study. We have determined (1) hyperplasia by cell growth curve and fluorescence activated cell sorting (FACS); and (2) ultrastructure by electron microscope observation; and (3) expressions of cyclin D2 mRNA and p16 mRNA by using in situ hybridization and image analysis. The results were shown (1) Results of cell growth curve and FACS analysis showed CM could proliferate in the first 3 cultured days (4 days in postnatal development). But the ability decreased quickly, concomitant with the differentiation. (2) The ultrastructure of CM showed the large amount of myofilaments and mitochondrion and FC showed moderate amount of rough endoplasmic reticulum. (3) The expression of cyclin D2 mRNA in 3-, 4-, 5-day CM group was 0.89 times(p<0.05), 0.80 times (p<0.05)and 0.56 times (p<0.01)of that in 1-day group respectively. P16 mRNA in 2-, 3-, 4-, 5-day CM group were 1.63 times(p<0.01),1.72 times(p<0.01),1.99 times (p<0.01)and 2.84 times (p<0.01) of that in 1-day group respectively. It can be concluded that cultured neonatal rat cardiac myocytes could proliferate during the first 3 cultured days, but the ability of proliferation decreased, from the fourth day, concomitant with differentiation. Cyclin D2 and p16 have the key roles during the transition from myocyte hyperplasia to hypertrophy.

  20. Determinants of Left Ventricular Mass and Hypertrophy in Hemodialysis Patients Assessed by Cardiac Magnetic Resonance Imaging

    Patel, Rajan K.; Oliver, Scott; Mark, Patrick B.; Powell, Joanna R.; Emily P. McQuarrie; Traynor, James P.; Dargie, Henry J.; Jardine, Alan G.


    Background and objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for premature cardiovascular death in hemodialysis (HD) patients and one of the three forms of uremic cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a volume-independent technique to assess cardiac structure. We used CMR to assess the determinants of left ventricular mass (LVM) and LVH in HD patients.

  1. Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes

    Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B. Cicero; Zarzoso, Manuel; Ramirez, Rafael J.; Sener, Michelle F.; Mundada, Lakshmi V.; Klos, Matthew; Devaney, Eric J.; Vikstrom, Karen L.; Herron, Todd J.; Jalife, José


    Applications of human induced pluripotent stemcell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricularmyocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. PMID:24095945

  2. Factors influencing left ventricular hypertrophy in children and adolescents with or without family history of premature myocardial infarction

    Seyyed Mohsen Hosseini


    Result : The results showed that among the studied variables, gender, age, body mass index, and blood pressure were associated with the left ventricular hypertrophy. Conclusion: Considering the results and previous studies in this field, it was observed that left ventricular hypertrophy exists at early ages, which is very dangerous and can lead to heart diseases at early ages. Factors such as being overweight, having high blood pressure, and being male cause left ventricular hypertrophy and lead to undiagnosable heart diseases.

  3. Effect of hydrogen peroxide on persistent sodium current in guinea pig ventricular myocytes

    Ji-hua MA; An-tao LUO; Pei-hua ZHANG


    Aim: To study the effect of hydrogen peroxide (H2O2) on persistent sodium current (INa.P) in guinea pig ventricular myocytes.Methods: The whole-cell, cell-attached, and inside-out patch-clamp techniques were applied on isolated ventricular myocytes from guinea pig.Results: H2O2 (0.1 mmol/L, 0.5 mmol/L and 1.0mmol/L) increased the amplitude of whole-cell INa.P in a concentration-dependent mmol/L) increased persistent sodium channel activity in cell-attached and insideout patches.The mean open probability was increased from control values of 0.015±0.004 and 0.012±0.003 to 0.106±0.011 and 0.136±0.010, respectively (P<0.01 vs control).They were then decreased to 0.039±0.024 and 0.027±0.006,respectively, after the addition of 1 mmol/L GSH (P<0.01 vs H2O2).The time when open probability began to increase and reached a maximum was shorter in insideout patches than that in cell-attached patches (4.8± 1.0 min vs 11.5±3.9 min, P<0.01;9.6±1.6 min vs 18.7±4.7 min, P<0.01).Conclusion: H2O2 increased the INa.P of guinea pig ventricular myocytes in a concentration-dependent manner, possibly by directly oxidating the cell membrane.

  4. Ca2+ paradox injury mediated through TRPC channels in mouse ventricular myocytes.

    Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi


    BACKGROUND AND PURPOSE The Ca(2+) paradox is an important phenomenon associated with Ca(2+) overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca(2+) paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performed on fluo-3 loaded quiescent mouse ventricular myocytes using confocal laser scanning microscope. KEY RESULTS The Ca(2+) paradox was readily evoked by restoration of the extracellular Ca(2+) following 10-20 min of nominally Ca(2+)-free superfusion. The Ca(2+) paradox was significantly reduced by blockers of transient receptor potential canonical (TRPC) channels (2-aminoethoxydiphenyl borate, Gd(3+), La(3+)) and anti-TRPC1 antibody. The sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine application, gradually declined during Ca(2+)-free superfusion, which was further accelerated by metabolic inhibition. Block of SR Ca(2+) leak by tetracaine prevented Ca(2+) paradox. The Na(+) /Ca(2+) exchange (NCX) blocker KB-R7943 significantly inhibited Ca(2+) paradox when applied throughout superfusion period, but had little effect when added for a period of 3 min before and during Ca(2+) restoration. The SR Ca(2+) content was better preserved during Ca(2+) depletion by KB-R7943. Immunocytochemistry confirmed the expression of TRPC1, in addition to TRPC3 and TRPC4, in mouse ventricular myocytes. CONCLUSIONS AND IMPLICATIONS These results provide evidence that (i) the Ca(2+) paradox is primarily mediated by Ca(2+) entry through TRPC (probably TRPC1) channels that are presumably activated by SR Ca(2+) depletion; and (ii) reverse mode NCX contributes little to the Ca(2+) paradox, whereas inhibition of NCX during Ca(2+) depletion improves SR Ca(2+) loading, and is associated with reduced incidence of Ca(2+) paradox in mouse ventricular myocytes.

  5. Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

    Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank


    Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

  6. [Left ventricular hypertrophy in hypertensive patients. Ultrasonic and physiopathology: therapeutic implications].

    Herpin, D; Raynier, P; Ciber, M; Amiel, A; Boutaud, P; Demange, J


    Hypertensive left ventricular hypertrophy can easily be diagnosed by echocardiography. It occurs in 30-50 per cent of hypertensive patients and has recently been shown to be a potent and independent predictor of morbidity and mortality, increasing the risk of sudden death, arrhythmia and severe coronary events. The condition usually presents as concentric left ventricular hypertrophy with symmetrically or asymmetrically thickened ventricular walls, but it may also be found with a dilated cavity. Its presence is a definite indication for active medical treatment. Guidelines for the choice of a particular antihypertensive drug are not yet available. Regression of the hypertrophy seems to be a rational goal of the treatment, but the beneficial effects of such a regression on left ventricular relaxation need further evaluation.

  7. Contribution of NHE-1 to cell length cardiac shortening of normal and failing rabbit myocytes

    M.M.G.J. van Borren; J.G. Zegers; A. Baartscheer; J.H. Ravesloot


    At the same intracellular pH (pH(i)) Na+/H+ exchange (NHE-1) fluxes of ventricular myocytes of hypertrophied failing hearts (HFH) are increased. We assessed how NHE-1 affected cell length shortening. pH(i) was measured fluorimetrically in resting and twitching (1 - 3 Hz)normal and HFH rabbit myocyte

  8. Consequences of reversal of hypertensive cardiac hypertrophy by captopril on left ventricular pumping ability and performance.

    Saragoça, M A; Cezaretti, M L; Bessa, A M; Casarini, D; Almeida, J B; Amorim, M P; Ramos, O L


    Left ventricular hypertrophy can be reversed by treatment of hypertension with captopril but the consequences of this regression are not yet fully described. We studied the maximal capacity of the hypertrophied and hypertrophy-reversed ventricle to generate pressure during transient total occlusion of the aorta, and also the left ventricular end-diastolic pressure required to meet this maximal effort. Two-kidney, one clip Goldblatt (renal hypertensive rats; RHR) hypertension was induced in 17 Wistar rats, eight of which were treated with captopril (RHR-C: 50 mg/kg given orally) from the fourth to the eighth week. Sham-operated controls (SC) remained untreated, or were treated with similar doses of captopril (SC-C). Significantly lower heart weights were found in RHR-C than in RHR (2.88 +/- 0.15 versus 2.38 +/- 0.04; P less than 0.001). During transient total occlusion of the aorta, the maximal intraventricular pressure developed in RHR-C was not significantly different from that in RHR, but left ventricular end-diastolic pressure was significantly less in RHR-C than in RHR (21.4 +/- 2.2 versus 34.3 +/- 3.8; P less than 0.01). The analysis of pressure-volume characteristics of the hypertrophied left ventricles and those in which hypertrophy was reversed revealed similar compliances between these two groups. Our data suggest that there was a mechanical improvement in the heart function after reversal of left ventricular hypertrophy.

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

    Sánchez-Chapula, J.


    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...

  10. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes.

    Hume, J R; Uehara, A


    Single myocardial cells were enzymatically dispersed from guinea-pig atria and ventricles. At 25 degrees C, atrial cell action potentials differed significantly from ventricular cell action potentials in duration (atrial = 141 ms, ventricular = 497 ms) and over-shoot (atrial = +36 mV, ventricular = +42 mV). Action potentials of atrial and ventricular cells responded differently to changes in external K+ concentration ([K+]o). Elevation of [K+]o from 6 to 11 mM depolarized atrial cells but produced no significant change in action potential duration; similar changes in [K+]o depolarized ventricular cells and produced a significant shortening of the action potential duration. Voltage-clamp experiments were performed to investigate the ionic basis underlying the different action potential configurations of single atrial and ventricular myocytes. A single-micropipette voltage-clamp technique was used, employing either extremely small-tip diameter pipettes, without internal cell dialysis (Hume & Giles, 1983), or larger tip diameter pipettes, with internal dialysis (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Two significant differences in background K+ conductance in single atrial and ventricular myocytes were observed: (i) the isochronal (5 s) current-voltage relationship of single ventricular myocytes exhibited a region of prominent negative slope conductance and elevation of [K+]o produced cross-over; a negative slope conductance region was absent in atrial cells and elevation of [K+]o produced very little cross-over of isochronal current-voltage relationships, and (ii) hyperpolarizing voltage pulses applied from holding potentials of -50 mV elicited inward current in ventricular cells which decayed with time; similar voltage-clamp pulses in atrial cells elicited inward currents which fail to decay. Single K+ channel current measurements confirmed the existence of different resting K+ channel properties in single atrial and ventricular myocytes. Resting K

  11. The Role of Obesity in the Development of Left Ventricular Hypertrophy Among Children and Adolescents.

    Brady, Tammy M


    Both obesity and hypertension have increased substantially among children over the last several decades. At the same time, mounting evidence has pointed to the role of these and other cardiovascular disease risk factors on the development of end organ damage such as left ventricular hypertrophy in children. While traditionally thought to occur in response to an increased afterload as in systemic hypertension, evidence demonstrates that obesity is associated with left ventricular hypertrophy independent of blood pressure. Both hemodynamic and non-hemodynamic factors contribute to the pathogenesis of obesity-related left ventricular remodeling. However, more contemporary research suggests that adiposity and blood pressure have a greater effect on left ventricular geometry when present together than when present alone. Normalization of left ventricular mass in obese hypertensive individuals requires achievement of both normotension and weight loss. Additional strategies are needed to promote the cardiovascular health of children, with greater emphasis placed on obesity prevention.

  12. Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

    Anderson, Robert H; Ho, Siew Yen; Sanchez-Quintana, Damian; Redmann, Klaus; Lunkenheimer, Paul P


    There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

  13. Tetrahydroacridine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes

    Wei WANG; Yi-ping WANG; Guo-yuan HU


    AIM: To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na+ channels in cardiac tissues.METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltagedependent Na+ current was recorded using whole cell voltage-clamp technique. RESULTS: (1) Tacrine reversibly inhibited Na+ current with an IC50 value of 120 μmol/L (95 % confidence range: 108-133 μmol/L). (2) The inhibitory effects of tacrine on Na+ current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 μmol/L caused a negative shift (about 10 mV) in the voltage-dependence of steady-state inactivation of Na+ current, and retarded its recovery from inactivation, but did not affect its activation curve. (4) Intracellular application of tacrine significantly inhibited Na+ current. CONCLUSION: In addition to blocking other voltage-gated ion channels,tacrine blocked Na+ channels in guinea-pig ventricular myocytes. Tactine acted as inactivation stabilizer of Na+channels in cardiac tissues.

  14. Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

    Lu-feng CHENG; Dong YAN; Subat TURDI; Parhat KERRAM


    Aim: To study the effects of haloperidol on sodium currents (INa) in guinea pig ventricular myocytes. Method: Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on INa, in individual ventricular myocytes.Results: Haloperidol (0.1-3 μmol/L) inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 μmol/L. The inhibition rate of haloperidol (0.3 μmol/L) on INa was 22.14%±0.02%, and the maximum conductance was reduced.Haloperidol significantly reduced the midpoints for the activation and inactiva-tion of INa by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%±1.4% (n=6); however, haloperidol at 0.03 μmol/L enhanced INa conductance. The mid-points for the activation and inactivation of INa were shifted by 1.38 and 5.69 mV,respectively, at this concentration of haloperidol.Conclusion: Haloperidol dis-played a biphasic effect on INa in guinea pig cardiac myocytes. High concentra-tions of haloperidol inhibited INa, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.

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

    Wachtell, K; Smith, G; Gerdts, E;


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

  16. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C


    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...... with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility....

  17. Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index

    Richard E. Tracy


    Full Text Available Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH. This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

  18. Laminar arrangement of ventricular myocytes influences electrical behavior of the heart.

    Hooks, Darren A; Trew, Mark L; Caldwell, Bryan J; Sands, Gregory B; LeGrice, Ian J; Smaill, Bruce H


    The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery.

  19. The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy

    Bacharova, Ljuba; Estes, Harvey E; Schocken, Douglas D


    The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended...... that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed....

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

    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia Gry


    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...... for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs....

  1. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Baptista, Ana, E-mail:; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)


    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

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

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


    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.

  3. Effect of resveratrol on L-type calcium current in rat ventricular myocytes

    Li-ping ZHANG; Jing-xiang YIN; Zheng LIU; Yi ZHANG; Qing-shan WANG; Juan ZHAO


    Aim: To study the effect of resveratrol on L-type calcium current (ICa-L) in isolated rat ventricular myocytes and the mechanisms underlying these effects. Methods:ICa-L was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. Results: Resveratrol (10-40 μmol/L) reduced the peak amplitude of ICa-L and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 μmol/L)decreased the peak amplitude of ICa-L from -14.2± 1.5 pA/pF to -10.5± 1.5 pA/pF (P<0.05), -7.5±2.4 pA/pF (P<0.01), and -5.2±1.2 pA/pF (P<0.01), respectively.Resveratrol (40 μmol/L) shifted the steady-state activation curve of ICa-L to the right and changed the half-activation potential (V0.5) from -19.4±0.4 mV to -15.4±1.9 mV (P<0.05). Resveratrol at a concentration of 40 μmol/L did not affect the steady-state inactivation curve of ICa-L, but did markedly shift the timedependent recovery curve of ICa-L to the right, and slow down the recovery of ICa-L from inactivation. Sodium orthovanadate (Na3VO4; 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). Conclusion: Resveratrol inhibited ICa- L mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.

  4. H⁺-activated Na⁺ influx in the ventricular myocyte couples Ca²⁺-signalling to intracellular pH.

    Garciarena, Carolina D; Youm, Jae Boum; Swietach, Pawel; Vaughan-Jones, Richard D


    Acid extrusion on Na(+)-coupled pH-regulatory proteins (pH-transporters), Na(+)/H(+) exchange (NHE1) and Na(+)-HCO3(-) co-transport (NBC), drives Na(+) influx into the ventricular myocyte. This H(+)-activated Na(+)-influx is acutely up-regulated at pHipH-transporter) with gap-junctions at intercalated discs. Overall Na(+)-influx via NBC is considerably lower, but much is co-localised with L-type Ca(2+)-channels in transverse-tubules. Through a functional coupling with Na(+)/Ca(2+) exchange (NCX), H(+)-activated Na(+)-influx increases sarcoplasmic-reticular Ca(2+)-loading and release during intracellular acidosis. This raises Ca(2+)-transient amplitude, rescuing it from direct H(+)-inhibition. Functional coupling is biochemically regulated and linked to membrane receptors, through effects on NHE1 and NBC. It requires adequate cytoplasmic Na(+)-mobility, as NHE1 and NCX are spatially separated (up to 60μm). The relevant functional NCX activity must be close to dyads, as it exerts no effect on bulk diastolic Ca(2+). H(+)-activated Na(+)-influx is up-regulated during ischaemia-reperfusion and some forms of maladaptive hypertrophy and heart failure. It is thus an attractive system for therapeutic manipulation. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".

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

    Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard


    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 (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......, 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...

  6. Dissociation enzyme effects on the biophysical properties of calcium current in acutely isolated rat ventricular myocytes

    Julio Álvarez


    Full Text Available Proteolytic enzymes such as collagenase, trypsin and pronase E are widely used to acutely dissociate adult cardiomyocytes. There is some evidence that enzyme treatment can alter ionic channels. The aim of the present investigation was to compare the characteristics of the L-type Ca2+ current (ICaL of rat ventricular cardiomyocytes dissociated with two enzyme combinations: collagenase + trypsin (C+T and collagenase + pronase E (C+P. ICaL density (pA/pF was significantly lower (~ 2 pA/pF in myocytes isolated with the C+P combination. However, its inactivation time course was barely affected. As well, the voltage dependency of ICaL kinetics was not affected by the C+P treatment. Our results suggest that, compared to the C+T, treatment with the C+P enzyme combination could decrease the number of functional (expressed channels in the sarcolemma.

  7. T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

    Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin


    In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF.

  8. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes.

    Chen, Kui-Hao; Liu, Hui; Yang, Lei; Jin, Man-Wen; Li, Gui-Rong


    SKF-96365 (1-(beta-[3-(4-methoxy-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) is a general TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in cardiovascular system. Recent reports showed that SKF-96365 induced a reduction in cardiac conduction. The present study investigates whether the reduced cardiac conduction caused by SKF-96365 is related to the blockade of voltage-gated sodium current (I Na) in rat ventricular myocytes using the whole-cell patch voltage-clamp technique. It was found that SKF-96365 inhibited I Na in rat ventricular myocytes in a concentration-dependent manner. The compound (1 μM) negatively shifted the potential of I Na availability by 9.5 mV, increased the closed-state inactivation of I Na, and slowed the recovery of I Na from inactivation. The inhibition of cardiac I Na by SKF-96365 was use-dependent and frequency-dependent, and the IC₅₀ was decreased from 1.36 μM at 0.5 Hz to 1.03, 0.81, 0.61, 0.56 μM at 1, 2, 5, 10 Hz, respectively. However, the selective TRPC3 antagonist Pyr3 decreased cardiac I Na by 8.5% at 10 μM with a weak use and frequency dependence. These results demonstrate that the TRPC channel antagonist SKF-96365 strongly blocks cardiac I Na in use-dependent and frequency-dependent manners. Caution should be taken for interpreting the alteration of cardiac electrical activity when SKF-96365 is used in native cells as a TRPC antagonist.

  9. Association of arterial stiffness and electrocardiography-determined left ventricular hypertrophy with left ventricular diastolic dysfunction.

    Po-Chao Hsu

    Full Text Available OBJECTIVES: Increased arterial stiffness is associated with left ventricular diastolic dysfunction (LVDD, but this association may be influenced by left ventricular (LV performance. Left ventricular hypertrophy (LVH is not only a significant determinant of LV performance, but is also correlated with LVDD. This study is designed to compare LV diastolic function among patients divided by brachial-ankle pulse wave velocity (baPWV and electrocardiography (ECG-determined LVH and to assess whether increased baPWV and ECG-determined LVH are independently associated with LVDD. METHODS: This cross-sectional study enrolled 270 patients and classified them into four groups according to the median value of baPWV and with/without ECG-determined LVH. The baPWV was measured using an ABI-form device. ECG-determined LVH was defined by Sokolow-Lyon criterion. LVDD was defined as impaired relaxation, pseudonormal, and restrictive mitral inflow patterns. Groups 1, 2, 3, and 4 were patients with lower baPWV and without ECG-determined LVH, lower baPWV but with ECG-determined LVH, higher baPWV but without ECG-determined LVH, and higher baPWV and with ECG-determined LVH respectively. RESULTS: Early diastolic mitral velocity (Ea was gradually decreased from group 1 to group 4 (p≦0.027. Patients in group 4 had the highest prevalence of LVDD (all p<0.001. After multivariate analysis, both baPWV and ECG-determined LVH were independent determinants of Ea (β = -0.02, P<0.001; β = -1.77, P<0.001 respectively and LVDD (odds ratio = 1.02, P = 0.011 and odds ratio = 3.53, P = 0.013 respectively. CONCLUSION: Our study showed the group with higher baPWV and ECG-determined LVH had the lowest Ea and highest prevalence of LVDD. In addition, both baPWV and ECG-determined LVH were independently associated with Ea and LVDD. Hence, assessment of arterial stiffness by baPWV and LVH by ECG may be useful in identifying the high risk group of LVDD.

  10. Marked left ventricular hypertrophy mimicking hypertrophic cardiomyopathy associated with steroid therapy for congenital adrenal hyperplasia.

    Scirè, Giuseppe; D'Anella, Giorgio; Cristofori, Laura; Mazzuca, Valentina; Cianfarani, Stefano


    We describe a child treated with high-dose steroid therapy for congenital adrenal hyperplasia who showed marked left ventricular hypertrophy mimicking hypertrophic cardiomyopathy associated with steroid therapy for congenital adrenal hyperplasia. Cardiomyopathy reversed completely when an appropriate steroid therapeutic regimen was established.

  11. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, O


    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...

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

    Westerhout, Cynthia M; Lauer, Michael S; Fu, Yuling


    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...

  13. Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

    Klatt, Niklas; Scherschel, Katharina; Schad, Claudia


    Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental...

  14. Left ventricular hypertrophy screening using a hand-held ultrasound device

    E.C. Vourvouri (Eleni); D. Poldermans (Don); A.F.L. Schinkel (Arend); L.Y. Koroleva; F. Sozzi (Fabiola); G.E. Parharidis; J.J. Bax (Jeroen); J.R.T.C. Roelandt (Jos)


    textabstractAIMS: To test the diagnostic potential of a hand-held ultrasound device for screening for left ventricular hypertrophy in a hypertensive population using a standard echocardiographic system as a reference. METHODS: One hundred consecutive hypertensive patients were enro

  15. Characteristics of the inward-rectifying potassium current in mouse ventricular myocytes and its relation to early after-depolarization

    周盈颖; 郝雪梅; 范劲松; 刘泰(木逢)


    The properties of the inward-rectifying potassium current (IK1) were studied in the single myocytes isolated from adult mouse ventricles by the whole-cell patch-damp technique for the first time. Most of the properties of IK1 including channel conductances, activation, inactivation, rectification and external K+ sensitivity in mouse ventricular myocyte were similar to those in other species, but the current-voltage (1-V) curve of mouse ventricular myocyte showed no negative slope, i.e the slope in the range of membrane potential 50 mV positive to the reversal potential (VRev) was virtually flat and remained at a low current level ((59±39) pA). Under the superfusion of Tyrode’s solution with 3mmol/L K+ and 3mmol/L Cs+, IK1 in the above region nearly decreased to zero, and then the early after-depolarization (EAD) occurred. The results suggest that this distinctive characteristic of IK1 in mouse ventricular myocyte may relate to the high susceptibility to EA0 in mouse myocardium. The inhibition of IK1 se

  16. Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans.

    Leenen, F H; Smith, D L; Farkas, R M; Reeves, R A; Marquez-Julio, A


    Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.

  17. Differences of promethazine and terfenadine on ion channels in guinea pig ventricular myocytes

    LI Xue-wen; NIU Shuan-cheng; ZHANG Xuan-ping; L(U) Ji-yuan; BAI Feng; ZHANG Ling; WU Bo-wei


    @@ Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias1 and experimental arrhythmias.2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes (TdP) like ventricular arrhythmia.3 This may be due to the blockage on rectifier postassium current (Ik) of terfenadine, resulting in the prolongation of the action potential duration (APD) and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the Ik and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.

  18. The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

    Xu, Hao; Zhao, Manxi; Liang, Shenghui; Huang, Quanshu; Xiao, Yunchuan; Ye, Liang; Wang, Qinyi; He, Longmei; Ma, Lanxiang; Zhang, Hua; Zhang, Li; Jiang, Hui; Ke, Xiao; Gu, Yuchun


    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases. PMID:27762288

  19. Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

    Walsh Michael


    Full Text Available Abstract Background Left ventricular (LV hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. Methods This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month. Agreement was assessed using Lin's concordance correlation coefficient (CCC and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC. Results Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80 predictive power for LV hypertrophy. Conclusions A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

  20. Ultrasonic evaluation of the relationship between left ventricular hypertrophy or left ventricular geometry and endothelial function in patients with essential hypertension

    Jing Dong; Pingyang Zhang; Xuehong Feng; Chong Wang; Pei Wang


    Objective: To assess the relationship between left ventricular hypertrophy (LVH) or left ventricular geometry (LVG) and endothelial function in patients with essential hypertension (EH). Methods: Seventy-six patients and 30 normal subjects were first examined by echocardiography. Brachial artery dilatation induced by reactive hyperemia (DIRH) or nitroglycerin (DING) was detected using high-resolution ultrasonography. Results: DIRH was lower in patients with hypertension than in the controls, and the decrease in DIRH was greater in the patients with LVH than that in patients without LVH (4.36±2.54% vs 8.56+1.87 %; P 0.05). While there was no significant difference in DIRH between the patients with normal left ventricular geometry or cardiac remodeling, the patients showing either eccentric or concentric left ventricular hypertrophy had lower DIRH than the patients with normal left ventricular geometry or cardiac remodeling. The DIRH was the lowest in patients with concentric hypertrophy. Although bivariate analysis showed that the left ventricular mass index (LVMI) correlated well with the brachial artery dilatation induced by reactive hyperemia, diastolic blood pressure and mean blood pressure (r=-0.61, P < 0.0001; r=0.27, P < 0.05; r=0.31, P < 0.05, respectively), a multivariate stepwise regression demonstrated that LVMI correlated only with the brachial artery dilatation induced by reactive hyperemia. Conclusion: Left ventricular hypertrophy was related to endothelial dysfunction in essential hypertension. The endothelial dysfunction might be basic and important in the progression of left ventricular hypertrophy.

  1. The evaluation of left ventricular hypertrophy in hypertensive patients with subclinical hyperthyroidism.

    Tamer, Ismet; Sargin, Mehmet; Sargin, Haluk; Seker, Mesut; Babalik, Erhan; Tekce, Mustafa; Yayla, Ali


    The aim of this prospective cross-sectional study was to investigate the hypertrophic effects of endogenous subclinical hyperthyroidism on myocardium and early development of left ventricular hypertrophy (LVH) in essential hypertensive patients accompanied by endogenous subclinical hyperthyroidism. A total of 31 consecutive patients with stage I hypertension were included in the study. Sixteen of them also had endogenous subclinical hyperthyroidism that they were unaware before. The patients and the controls formed out of ten healthy subjects all underwent an investigation of thyroid functions and cardiologic evaluation. The mean wall thickness of the left ventricle in the stage I hypertensive group with endogenous subclinical hyperthyroidism (group I) was significantly increased as compared with both hypertensive patients without thyroid disease (group II) and the control subjects. The mean left ventricle mass was also significantly higher in group I than group II. Both of the patients' groups had an increased prevalence of LVH as compared with the controls. In this study, hypertensive patients with subclinical hyperthyroidism presented more increase in left ventricular mass, suggesting that subclinical hyperthyroidism may contribute to left ventricular hypertrophy forming a natural progression to hypertension. The hypertensive population should always be screened for endogenous subclinical hyperthyroidism, and should be examined for the criteria of left ventricular hypertrophy by echocardiography in early stages.

  2. The Relation Between Hypertrophied Myocardium and Ventricular Fibrillation Threshold in Spontaneously Hypertensive Rats

    Huang Zhibin; Wu Wei; Deng Yijun; Fang Chang; Wei Yulin; Zhou Shuxian; Wang Jingfeng


    Objectives To investigate the relation between hypertrophied myocardium and ventricular fibrillation threshold in spontaneously hypertensive rats (SHR). Methods 20 male SHR were randomly divided into two groups: 10 week group (n=10) and 18 week group (n=10). 10week male Wistar rats were controlled group (n=10). The systolic blood pressure (SBP), heart mass index (HMI), ventricular effective refractory period (VERP) and ventricular fibrillation threshold(VFT) were measured respectively.Results ① The SBP and HMI of SHR were significantly higher than those of Wistar rats(P<0.001).The VFT of SHR were significantly lower than that of Wistar rats (P < 0.001). ②In SHR, the SBP and HMI of 18 week SHR were significantly higher than those of 10 week SHR (P < 0.001). The VFT of 18 week SHR were significantly lower than that of 10 week SHR (P<0.001). ③There were no significant difference of VERP among 10 week SHR, 18 week SHR and Wistar rats(P > 0.05). ④There was no relationship between HMI and VFT or SBP in Wistar rats. There was significant relationship between HMI and VFT or SBP in different age spontaneously hypertensive rats. ⑤HMI, age and species of animal were the major influent factors of VFT. Conclusions The VFT of hypertrophied myocardium decreased. The higher the degree of hypertrophy of myocardium and the higher the systolic blood pressure were, the lower the ventricular fibrillation threshold was.

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

    Vildbrad, Mads D; Andersen, Asger; Holmboe, Sarah;


    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....... 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...

  4. Xanthohumol Modulates Calcium Signaling in Rat Ventricular Myocytes: Possible Antiarrhythmic Properties.

    Arnaiz-Cot, Juan Jose; Cleemann, Lars; Morad, Martin


    Cardiac arrhythmia is a major cause of mortality in cardiovascular pathologies. A host of drugs targeted to sarcolemmal Na(+), Ca(2+), and K(+) channels has had limited success clinically. Recently, Ca(2+) signaling has been target of pharmacotherapy based on finding that leaky ryanodine receptors elevate local Ca(2+) concentrations causing membrane depolarizations that trigger arrhythmias. In this study, we report that xanthohumol, an antioxidant extracted from hops showing therapeutic effects in other pathologies, suppresses aberrant ryanodine receptor Ca(2+) release. The effects of xanthohumol (5-1000 nM) on Ca(2+) signaling pathways were probed in isolated rat ventricular myocytes incubated with Fluo-4 AM using the perforated patch-clamp technique. We found that 5-50 nM xanthohumol reduced the frequency of spontaneously occurring Ca(2+) sparks (>threefold) and Ca(2+) waves in control myocytes and in cells subjected to Ca(2+) overload caused by the following: 1) exposure to low K(+) solutions, 2) periods of high frequency electrical stimulation, 3) exposures to isoproterenol, or 4) caffeine. At room temperatures, 50-100 nM xanthohumol reduced the rate of relaxation of electrically- or caffeine-triggered Ca(2+)transients, without suppressing ICa, but this effect was small and reversed by isoproterenol at physiologic temperatures. Xanthohumol also suppressed the Ca(2+) content of the SR and its rate of recirculation. The stabilizing effects of xanthohumol on the frequency of spontaneously triggered Ca(2+) sparks and waves combined with its antioxidant properties, and lack of significant effects on Na(+) and Ca(2+) channels, may provide this compound with clinically desirable antiarrhythmic properties.

  5. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

    Dweck Marc R


    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR is the gold standard non-invasive method for determining left ventricular (LV mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male with aortic stenosis (aortic valve area 0.93±0.32cm2 were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43 and pattern (P=0.22 of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02. Six patterns of LV adaption were observed: normal ventricular geometry (n=11, concentric remodeling (n=11, asymmetric remodeling (n=11, concentric hypertrophy (n=34, asymmetric hypertrophy (n=14 and LV decompensation (n=10. Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration Reference Number: NCT00930735

  6. Effects of Losartan on L-type Calcium Current in Hypertrophied RatMyocytes

    FuLiying; LiYang; ChengLan; WangFang; XiaGuojin; YaoWeixing


    Objective To investigate the alterations of L-type calcium current (IcaL) in abdominal aorticligation-induced hypertrophied rat hearts and the effect of losartan on these alterations. METHODS Cardiachypertrophy was induced by abdominal aortic ligation in rats. To record IcaL, whole-cell patch-clamp technique wasused. RESULTS Membrane capacitance was larger in hypertrophied cells (148±29 pF) than in sham-operated cells(102±14 pF, P<0.01) and losartan-treated cells (118±27, P<0.01). The maximal peak IcaL Was increased from-835±124 pA in sham-operated cells to -1404+_417 pA in hypertrophied cells (P<0.01), the corresponding IcaL density was increased from -7.5±1.8 pA.pF1 to -10.5±2.2 pA.pF1 (P<0.01), while they were reduced to -956-2:170pF (P<0.01) and -8.2±1.6 pA.pF1 (P<0.05) respectively in losartan-treated cells. The membrane potential of halfmaximal activation of the hypertrophied cells (-20.6±1.0 mV) shifted to more negative potentials than sham-operatedcells (-15.6±1.6 mV, P<0.01) and lorsartan-treated cells (-17.4±1.0 mV, P<0.01). The slope of the activation curveof hypertrophied cells (5.7±0.4) was decreased slightly than sham-operated cells (6.4±0.5, P<0.05). The membranepotential of half maximal inactivation of hypertrophied cells (-27.6±1.9 mV) shifted to more positive potentials thansham-operated cells (-31.4±2.2 mV, P<0.05). The slope of inactivation curves were not different in the three groups.

  7. Wnt5a attenuates hypoxia-induced pulmonary arteriolar remodeling and right ventricular hypertrophy in mice.

    Jin, Yuling; Wang, Wang; Chai, Sanbao; Liu, Jie; Yang, Ting; Wang, Jun


    Hypoxic pulmonary hypertension (HPH), which is characterized by pulmonary arteriolar remodeling and right ventricular hypertrophy, is still a life-threatening disease with the current treatment strategies. The underlying molecular mechanisms of HPH remain unclear. Our previously published study showed that Wnt5a, one of the ligands in the Wnt family, was critically involved in the inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of β-catenin/cyclin D1 in vitro. In this study, we investigated the possible functions and mechanisms of Wnt5a in HPH in vivo. Recombinant mouse Wnt5a (rmWnt5a) or phosphate buffered saline (PBS) was administered to male C57/BL6 mice weekly from the first day to the end of the two or four weeks after exposed to hypoxia (10% O2). Hypoxia-induced pulmonary hypertension was associated with a marked increase in β-catenin/cyclin D1 expression in lungs. Right ventricular systolic pressure and right ventricular hypertrophy index were reduced in animals treated with rmWnt5a compared with PBS. Histology showed less pulmonary vascular remodeling and right ventricular hypertrophy in the group treated with rmWnt5a than with PBS. Treatment with rmWnt5a resulted in a concomitant reduction in β-catenin/cyclin D1 levels in lungs. These data demonstrate that Wnt5a exerts its beneficial effects on HPH by regulating pulmonary vascular remodeling and right ventricular hypertrophy in a manner that is associated with reduction in β-catenin/cyclin D1 signaling. A therapy targeting the β-catenin/cyclin D1 signaling pathway might be a potential strategy for HPH treatment.

  8. Mechanism for Muscarinic Inhibitory Regulation of the L-type Ca2 + Current in Cardiac Ventricular Myocytes

    蒋彬; 杨向军; 惠杰; 蒋廷波; 宋建平; 刘志华


    @@ Objective The autonomic nervous system plays a key role in regulating cardiac function by modifying heart rate, contractility and impulse. The parasympathetic neurotransmitter acetyl-choline and muscarinic agonist carbachol (Cch) inhibit excitation-contraction coupling in cardiac ventricular myocytes. Muscarinic agonists suppress adenylyl cyclase (AC) acitivity and,by reducing activation of the cAMP/protein kinase A (PKA)cascade, inhibit the L-type Ca2+ current (ICa(L) ). They also increase the content of cGMP by stimulating guanylyl cyclase (GC) activity. The role of nitric oxide (NO)/cGMP in muscarinic inhibition has undergone considerable scrutiny. The role of the NO/cGMP pathway in the inhibition of ICa(L) by Cch was examined in guinea-pig ventricular myocytes.

  9. Metoprolol treatment lowers thrombospondin-4 expression in rats with myocardial infarction and left ventricular hypertrophy.

    Mustonen, Erja; Leskinen, Hanna; Aro, Jani; Luodonpää, Marja; Vuolteenaho, Olli; Ruskoaho, Heikki; Rysä, Jaana


    Thrombospondins are matrix proteins linked to extracellular matrix remodelling but their precise role in the heart is not known. In this study, we characterised left ventricular thrombospondin-1 and -4 expression in rats treated with a beta-blocker metoprolol during the remodelling process in response to pressure overload and acute myocardial infarction. Left ventricular thrombospondin-1 and thrombospondin-4 mRNA levels increased 8.4-fold (p infarction, respectively. Metoprolol infusion by osmotic minipumps (1.5 mg/kg/hr) for 2 weeks after myocardial infarction decreased thrombospondin-1 and thrombospondin-4 mRNA levels (55% and 50%, respectively), improved left ventricular function, and attenuated left ventricular remodelling with reduction of left ventricular atrial natriuretic peptide and brain natriuretic peptide gene expression. Thrombospondin-1 and -4 mRNA levels correlated positively with echocardiographic parameters of left ventricular remodelling as well as with atrial natriuretic peptide and brain natriuretic peptide gene expression. Moreover, there was a negative correlation between left ventricular ejection fraction and thrombospondin-1 mRNA levels. In 12-month-old spontaneously hypertensive rats with left ventricular hypertrophy, metoprolol decreased left ventricular thrombospondin-4 levels and attenuated remodelling while thrombospondin-1, atrial natriuretic peptide and brain natriuretic peptide mRNA levels as well as left ventricular function remained unchanged. In metoprolol-treated spontaneously hypertensive rats, thrombospondin-4 gene expression correlated with parameters of left ventricular remodelling, while no correlations between thrombospondins and natriuretic peptides were observed. These results indicate that thrombospondin-1 expression is linked exclusively to left ventricular remodelling process post-infarction while thrombospondin-4 associates with myocardial remodelling both after myocardial infarction and in hypertensive heart disease

  10. Modulation of KATP currents in rat ventricular myocytes by hypoxia and a redox reaction

    Xi-sheng YAN; Ji-hua MA; Pei-hua ZHANG


    Aim:The present study investigated the possible regulatory mechanisms of redox agents and hypoxia on the K_(ATP) current (I_(KATP)) in acutely isolated rat ventricular myocytes.Methods: Single-channel and whole-cell patch-clamp techniques were used to record the K_(ATP) current (I_(KATP)) in acutely isolated rat ven-tricular myocytes.Results: Oxidized glutathione (GSSG, 1 mmol/L) increased the I_(KATP), while reduced glutathione (GSH, 1 mmol/L) could reverse the increased I_(KATP) during normoxia. To further corroborate the effect of the redox agent on the KATP channel, we employed the redox couple DTT (1 mmol/L)/H_2O_2 (0.3, 0.6, and 1 mmol/L) and repeated the previous processes, which produced results similar to the previous redox couple GSH/GSSG during normoxia. H_2O_2 increased the I_(KATP) in a concentration dependent manner, which was reversed by DTT (1 mmol/L). In addition, our results have shown that 15 min of hypoxia increased the I_(KATP), while GSH (1 mmol/L) could reverse the increased I_(KATP). Furthermore, in order to study the signaling pathways of the I_(KATP) augmented by hypoxia and the redox agent, we applied a protein kinase C(PKC) inhibitor bisindolylmaleimide VI (BIM), a protein kinase G(PKG) inhibitor KT5823, a protein kinase A (PKA) inhibitor H-89, and Ca(2+)/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibitors KN-62 and KN-93. The results indicated that BIM, KT5823, KN-62, and KN-93, but not H-89, inhibited the IKATPaugmented by hypoxia and GSSG; in addition, these results sug-gest that the effects of both GSSG and hypoxia on K_(ATP) channels involve the activation of the PKC, PKG, and CaMK Ⅱ pathways, but not the PKA pathway.Conclusion: The present study provides electrophysiological evidence that hypoxia and the oxidizing reaction are closely related to the modulation of I_(KATP).

  11. Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes

    LI Ning; MA Ke-juan; WU Xiang-feng; SUN Qi; ZHANG Yi-hui; PU Jie-lin


    Background Shensong Yangxin (SSYX) is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current (INa), L-type calcium current (ICa,L), transient outward potassium current (Ito), delayed rectifier current (IK), and inward rectifier potassium currents (IK1) in isolated ventricular myocytes.Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes.Results SSYX decreased peak INa by (44.84±7.65)% from 27.21±5.35 to 14.88±2.75 pA/pF (n=5, P<0.05). The medicine significantly inhibited the ICa,L. At concentrations of 0.25, 0.50, and 1.00 g/100 mi, the peak ICa,L was reduced by(19.22±1.10)%, (44.82±6.50)% and (50.69±5.64)%, respectively (n=5, all P<0.05). SSYX lifted the Ⅰ-Ⅴ curve of both INa and ICa,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of Ito by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of IK was decreased by (30.77±1.11)% (n=5,P<0.05) at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of IK was also inhibited. Similar to the effect on IK, the SSYX inhibited IK1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property.Conclusions The experiments revealed that SSYX could block multiple ion channels such as INa ICa,L, Ik, Ito and IK1,which may change the action potential duration and contribute to some of its antiarrhythmic effects.

  12. Effects of Matrine on Aconitine-Induced Electrophysiological Changes in Rat Ventricular Myocytes

    SHANHong-li; YANGBao-feng; ZHOUYu-hong; WANGHe; LIBao-xin


    Aim To explore the reason that the antiarrhythmic effect of the extract of traditional Chinese medicinal herb, matrine, is weaker than quinidine and verapamil by comparision of the effect and efficacy of matrine on various kinds of transmembrane ionic currents with those of quinidine and verapamil; and to demonstrate the best targets for antiarrhythinic drugs. Methods Whole-cell patch-clamp techniques were used to record the action potential and ionic currents in single cells of rat ventrictdar myocytes. Aconitine was used to induce the changes of ionic currents, then study the effects of matrine and quinidine, verapamil on aconitine-induced imbalanced channel currents and action potential. Results Aconitine 1μmol·L-1 induced significant changes in transmembrane currents and action potential in single cells of rat ventricular myocytes. APD was significantly prolonged by aconitine. Simtdtaneously, aconitine increased sodium, L-type calcium and in-ward rectifier potassium currents. Matrine 100μmol·L-1 reversed the aconitine-induced changes of sodium current (INa)from (-70.2±10.5) pA/pF to (-39.6±4.0) pA/pF (n=5, P<0.05 vs aconitine) ; L-type calcium current (ICa-L)from (20.4±3.8) pA/pF to (-12.9±2.9) pA/pF (n=6, P<0.01); the inward rectifier potassium current (IK1) from (-32.2±1.08) pA/pF to (-24.0±3.4) pA/pF (n=6, P<0.01 ), and action potential duration. The reversal effectsof quinidine and verapamil on aconitine-induced changes of APD and ionic currents were more marked than matrine. Conclusion Aco-nitine significantly disturbs the normal equilibrium of ion channels in ventricular myecytes. It induces changes of INa, ICa-L, IK1 and prolongation of action potential duration. Matrine at concentration 50 or 100μmol·L-1 statistically significantly suppresses aconitine-induced changes of APD and ionic currents. The potency and efficacy of inhibitory effect of matrine are markedly weaker than those of commonly used verapamil and quinidine.

  13. Characteristics of the Nonselective Cation Current (NSCCs) in Rabbit Left Ventricular Epicardial, Midmyocardial and Endocardial Myocytes

    Min Zong; Xinchun Yang; Xiulan Liu; Liang Shi; Taifeng Liu


    Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine,feline,rat,guinea pig,and human hearts.This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca ) and late INa in M region (deep subepicardial to midmyocardial).Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes.Methods We examined the characteristics of NSCCs in epicardial,M region,and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques.The permeability to Na+,K + ,Li + ,Cs + but not to Cl-indicating that it was a nonselective cation current.Gd3+ (0.1 mmol/1) and La3+ (0.1 mmol/1) can block the current markedly.Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells.NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells.With repolarization to-80 mV,INs current density was (-0.44 ±0.05) PA/PF in endocardial cells,(-0.12 ±0.05) PA/PF in M cells and (-0.28 ±0.07) PA/PF in epicardial cells;and with repolarization to + 30 mV,INs current density was ( 1.09 ± 0.29) PA/PF in endocardial cells,(0.38 ± 0.09) PA/PF in M cells and (0.91 ± 0.32) PA/PF in epicardial cells.Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial,endocardial myocytes and M cells.These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.

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

    Wachtell, K.; Devereux, R.B.; Lyle, P.A.;


    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...

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

    Chiranjivi Potu


    Full Text Available 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 (RWT can be used to identify different left ventricular geometrical patterns. Various indexation methods normalised for LVM have been shown to offer prognostic significance. There was no prior study on the prevalence of LVH and geometric patterns in hypertensive patients in Jamaica using multiple partition values. Our study was designed to estimate the prevalence of LVH and geometrical patterns in a hypertensive Caribbean population in Jamaica using 10 different published cut-off values.

  16. Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in Spontaneously Hypertensive Rats

    韩少杰; 郑智; 任大宏


    Summary: Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy(LVH) and its possible mechanism-inhibiting the action of cardiac aldosterone in spontaneouslyhypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRswere used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pres-sure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stainedwith HE method and VanGieson method. Collagen volume fraction was determined in the left ven-tricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measuredby radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited high-er SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P<0. 05).After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, andaldosterone concentration in SHR were decreased as compared with control group (P<0. 05) ex-cept SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ven-tricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. Themechanism was probably related with the inhibition of the cardiac aldosterone action.

  17. Lung function and left ventricular hypertrophy in morbidly obese candidates for bariatric surgery

    Müller, Paulo de Tarso; Domingos, Hamilton; Patusco, Luiz Armando Pereira; Rapello, Gabriel Victor Guimarães


    Objective: To look for correlations between lung function and cardiac dimension variables in morbidly obese patients, in order to test the hypothesis that the relative size of the small airways is independently correlated with left ventricular hypertrophy. Methods: This was a retrospective study involving 192 medical records containing a clinical protocol employed in candidates for bariatric surgery between January of 2006 and December of 2010. Results: Of the 192 patients evaluated, 39 (10 males and 29 females) met the inclusion criteria. The mean BMI of the patients was 49.2 ± 7.6 kg/m2, and the mean age was 35.5 ± 7.7 years. The FEF25-75/FVC, % correlated significantly with left ventricular posterior wall thickness and relative left ventricular posterior wall thickness, those correlations remaining statistically significant (r = −0.355 and r = −0.349, respectively) after adjustment for weight, gender, and history of systemic arterial hypertension. Stepwise multivariate linear regression analysis showed that FVC and FEV1 were the major determinants of left ventricular mass (in grams or indexed to body surface area). Conclusions: A reduction in the relative size of the small airways appears to be independently correlated with obesity-related cardiac hypertrophy, regardless of factors affecting respiratory mechanics (BMI and weight), gender, or history of systemic arterial hypertension. However, FEV1 and FVC might be important predictors of left ventricular mass in morbidly obese individuals. PMID:26578134


    Evgenia Innokentyevna Markelova


    Full Text Available Objective — to evaluate potential input of different factors in the development of left ventricular hypertrophy (LVH in patients with gout. Material and methods. 57 male patients with gout were included into the study. Echocardiography was performed in M- and B-modes and left ventricular myocardial mass index (LVMMI was calculated for each patient. LVH was defined as LVMMI >115 g/m 2. Results. LVH was detected in 23 (40,4% out of 57 patients. LVH was associated with advanced age, arterial hypertension, obesity, hyperuricemia and increased C-reactive protein levels.

  19. Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

    Benoist, David; Stones, Rachel; Drinkhill, Mark; Bernus, Olivier; White, Ed


    Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time R...

  20. Ca(2+)-activated chloride channel activity during Ca(2+) alternans in ventricular myocytes.

    Kanaporis, Giedrius; Blatter, Lothar A


    Cardiac alternans, defined beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias. We investigated mechanisms of cardiac alternans in single rabbit ventricular myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. A strong correlation between beat-to-beat alternations of AP morphology and CaT alternans was observed. During CaT alternans application of voltage clamp protocols in form of pre-recorded APs revealed a prominent Ca(2+)-dependent membrane current consisting of a large outward component coinciding with AP phases 1 and 2, followed by an inward current during AP repolarization. Approximately 85% of the initial outward current was blocked by Cl(-) channel blocker DIDS or lowering external Cl(-) concentration identifying it as a Ca(2+)-activated Cl(-) current (ICaCC). The data suggest that ICaCC plays a critical role in shaping beat-to-beat alternations in AP morphology during alternans.

  1. Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

    Hong-Bo Liu; Chun-Hua Lin; Guang-Yu Zhou; Guo-Zhen Chen; Wei-Yan Cai


    Objective:To investigate the effects ofXinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.Methods:SixtyWistar rats were randomly divided into four groups.The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method.Rats inA andB groups were intragastrically administered with physiological saline, whileC andD groups were administered withXinjikang and metoprolol, respectively.The changes in blood pressure,E/A ratio, myocardial pathological morphology, myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment. Results:There were statistically significant differences inE/A ratio betweenC group after treatment and model group(P0.05); after treatment the myocardial lipoperoxides and superoxide dismustase contents inC andD groups were improved significantly compared with model group(P<0.05).Conclusions:Xinjikang can improve myocardial injury, restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.

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

    Celso Ferreira Filho


    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 β1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  3. The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi [Gunma Prefectural Cardiovascular Center (Japan)] (and others)


    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with {sup 123}I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting {sup 201}Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced {sup 201}Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

  4. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

    Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin


    The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (ICa,L) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). ICa,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased ICa,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced ICa,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, ICa,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases.

  5. Effects of remifentanil on intracellular Ca2+ and its transients induced by electrical stimulation and caffeine in rat ventricular myocytes

    ZHANG Ye; Michael G. Irwin; LI Rui; CHEN Zhiwu; Tak-Ming Wong


    Background Preconditioning with remifentanil confers cardioprotection. Since Ca2+ overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca2+ ([Ca2+]I) and its transients induced by electrical stimulation and caffeine, which reflects Ca2+ handling by Ca2+ handling proteins, in rat ventricular myocytes. Methods Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca]I was determined by spectrofluorometry. Remifentanil at 0.1-1000 μg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca2+]I, and the amplitude, time resting and 50% decay (t50) of both transients induced by electrical stimulation (E[Ca2+]I) and caffeine (C[Ca2+]I) were determined.Results Remifentanil (0.1-1000.0 μg/L) decreased the [Ca2+]I in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t50 of both transients dose-dependently.Conclusion Remifentanil reduced the [Ca2+]I and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

  6. Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

    Nie Xin; Shi Yiwei; Yu Wenyan; Xu Jianying; Hu Xiaoyun; Du Yongcheng


    Background Phosphatase and tensin homologue on chromosome ten (PTEN) acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10% oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.

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

    Bonomini, M. P.; Ingallina, F.; Barone, V.; Valentinuzzi, M. E.; Arini, P. D.


    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 = δ + β (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 specifity 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.

  8. Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

    Narita, Michihiro; Kurihara, Tadashi [Sumitomo Hospital, Osaka (Japan)


    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress {sup 99m}Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest {sup 123}I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and {sup 123}I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by {sup 123}I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in {sup 123}I-BMIPP). Eighteen normotensive patients with apical defect by {sup 123}I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by {sup 123}I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by {sup 123}I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and {sup 123}I-BMIPP imaging are useful for the identification of these patients. (author)

  9. β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model.

    Negroni, Jorge A; Morotti, Stefano; Lascano, Elena C; Gomes, Aldrin V; Grandi, Eleonora; Puglisi, José L; Bers, Donald M


    A five-state model of myofilament contraction was integrated into a well-established rabbit ventricular myocyte model of ion channels, Ca(2+) transporters and kinase signaling to analyze the relative contribution of different phosphorylation targets to the overall mechanical response driven by β-adrenergic stimulation (β-AS). β-AS effect on sarcoplasmic reticulum Ca(2+) handling, Ca(2+), K(+) and Cl(-) currents, and Na(+)/K(+)-ATPase properties was included based on experimental data. The inotropic effect on the myofilaments was represented as reduced myofilament Ca(2+) sensitivity (XBCa) and titin stiffness, and increased cross-bridge (XB) cycling rate (XBcy). Assuming independent roles of XBCa and XBcy, the model reproduced experimental β-AS responses on action potentials and Ca(2+) transient amplitude and kinetics. It also replicated the behavior of force-Ca(2+), release-restretch, length-step, stiffness-frequency and force-velocity relationships, and increased force and shortening in isometric and isotonic twitch contractions. The β-AS effect was then switched off from individual targets to analyze their relative impact on contractility. Preventing β-AS effects on L-type Ca(2+) channels or phospholamban limited Ca(2+) transients and contractile responses in parallel, while blocking phospholemman and K(+) channel (IKs) effects enhanced Ca(2+) and inotropy. Removal of β-AS effects from XBCa enhanced contractile force while decreasing peak Ca(2+) (due to greater Ca(2+) buffering), but had less effect on shortening. Conversely, preventing β-AS effects on XBcy preserved Ca(2+) transient effects, but blunted inotropy (both isometric force and especially shortening). Removal of titin effects had little impact on contraction. Finally, exclusion of β-AS from XBCa and XBcy while preserving effects on other targets resulted in preserved peak isometric force response (with slower kinetics) but nearly abolished enhanced shortening. β-AS effects on XBCa and XBcy

  10. Ettects of simvastatin on ion channel currents in ventricular myocytes from rabbit with acute myocardial infarction

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang


    Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acutemyocardial infarction( as to explore the ionic mechanism of statin treatment for antiarrhythmia.Methods Fourty-five NewZeland rabbits were randomly divided into three groups:AMI group,simvastatin intervention group(statin group)and sham-operatedcontrol group (CON).Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oralisolated enzymatically from the epicardial zone of the infractcd region.Whole cell patch clamp technique was used to record mmbranewas significantly decreased in AMI group(-23.26+5.1 8)compared with CON(-42.78±5.48,P<0.05),while it was significantlyincreased in Stating roup(-39.23±5.45)compared with AMI group(P<0.01);The peak Ica-L current density(at 0 mV) was significantlydecreased in AMI group(-3.23±0.91)compared with CON(-4.56±1.01,P<0.05),while it was significantly increased in Statin group(-4.18±0.95)compared with AMI group(P<0.05);The Ito current density(at+60 mV)was significantly decreased in AMI group(10.41±1.93)compared with CON(17.41±3.13,P<0.01),while it was significantly increased in Statin group(16.21±2.42)compared withattenuate this change without lowering the serum cholesterol level,suggesting that simvastatin reverse this electrical remodeling thuscontributing to the ionic mechanism of statin treatment for antiarrhythmia.

  11. A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.

    Vladimir E Bondarenko

    Full Text Available The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca(2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol. The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca(2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca(2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca(2+]i transients; changes in intracellular and transmembrane Ca(2+ fluxes; and [Na(+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca(2+]i transients. In particular, the model includes two subpopulations of the L-type Ca(2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca(2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of

  12. Ca2+ sparks evoked by depolarization of rat ventricular myocytes involve multiple release sites

    ZANGWei-Jin; YUXiao-Jiang; ZANGYi-Min


    AIM:To investigate the fundamental nature of calcium release events (Ca2+‘sparks’) evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling. METHODS: High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca2+ sparks and sparks evoked by depolarization. RESULTS: 1)Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35mV appeared to arise at single sites spacing about 1.80μm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at halfmaximal amplitude:FWHM) followed single Gaussian distributions with means of 2.6μm. 2)Different to this,transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9μm for spontaneous sparks and ith means of 1.9 and 3.1 μm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca2+ sparks evoked by depolarization are not ′unitary′ events, but often involve multiple sites of origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca2+ released during sparks directly triggered by influx through L-type Ca2+ channels may, in turn, trigger neighboring sites. The restricted involvement of only a few transverse release sites preserves the essential feature of the ‘local control’ theory of E-C coupling.

  13. [Structural and metabolic aspects of heterogenicity of the ventricular cardiac myocytes in coronary insufficiency].

    Gavrish, A S; Blagodarov, V N; Verbitskiĭ, V V; Danilishina, M V


    The paper shows comparative analysis of structural-metabolic changes of the ventricular cardiac hystiocytes during transitional restriction of blood supply, which leads to relapsing myocardium hypoperfusion, ischemia and even to cardiac infarction. We have established that an increase of the myocardium arrhythmogenicity, damage of myocardium electrophysiological activity and coronary deficiency are caused by pathologically intensified structural-metabolic heterogeneity of cardiomyocites. The chronic ischemic heart disease is worsening the situation by gradual accumulation of the metastructure changes of heart's working cells. It is possible to connect adaptable hypertrophy of cardiomyocites with compensatory redistribution of loading among them, what is accompanied with the deep reorganization of their metabolism and metastructure under the influence of neurohumoral factors, inadequate transport-trophic maintenance of the function, nonequal edema and fibrosis of the interstitium. The data obtained describe the formation of "prereadiness" of the myocardium to the fatal rhythm disturbance determined by interconnected structural-metabolic changes. Each of these pathological changes separately doesn't induce an impairment of myocardium electric stability but represents a necessary part in origin and development of the pathological process.

  14. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.


    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  15. Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats

    WANG Sheng; FEI Ke; XU Ya-wei; WANG Liang-xu; Chen Yan-qin


    Background Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. Methods Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. Results LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dtmax. Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. Conclusions Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.

  16. Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.

    Luo, Antao; Ma, Jihua; Song, Yejia; Qian, Chunping; Wu, Ying; Zhang, Peihua; Wang, Leilei; Fu, Chen; Cao, Zhenzhen; Shryock, John C


    An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, but the densities of INa.L and thus the potential relative contributions of this current to sodium ion (Na(+)) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch-clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in left atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 μM) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.

  17. Evaluation of left ventricular eccentric hypertrophy by /sup 201/Tl-myocardial scintigraphy

    Yamazaki, Junichi; Kawamura, Yasuaki; Okuzumi, Ichio; Morishita, Takeshi; Koyama, Nobuya; Komatsu, Hisashi; Ohsawa, Hidefumi; Yabe, Yoshimasa


    In order to elucidate the mechanism of left ventricular eccentric hypertrophy in conditions of volume overload, Tl-201 myocardial scintigraphy was performed in patients with aortic valve regurgitation and mitral valve regurgitation. There was a good relationship between the severity of Tl-defects, as determined by Tl-201 myocardial scintigraphy, and the changes in the T wave on the ECG on the one hand and the NYHA functional classification of heart diseases. In 17 of 18 patients where LVDd increased with increasing severity of Tl-defects and the defects were moderate to severe, LVDd was 65 mm or larger. There was a significant negative correlation between the washout rate for the whole circumference of the left ventricle, as determined by exercise Tl-201 SPECT, and LVDd (r=-0.603, p<0.01). The phenomenon of redistribution as determined by exercise Tl-201 myocardial scintigraphy was observed relatively early. Our results suggest that mechanical volume overload and ischemic changes are involved in left ventricular wall damage in left ventricular eccentric hypertrophy. For patients with moderate to severe Tl-defects valve replacement is indicated, no matter whether they may have heart failure or arrhythmia.

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

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


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

  19. Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy.

    Stanley, William C; Cox, James W; Asemu, Girma; O'Connell, Kelly A; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hoag, Stephen W; Rastogi, Sharad; Sabbah, Hani N; Daneault, Caroline; des Rosiers, Christine


    Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.

  20. Block of the delayed rectifier current (IK) by the 5-HT3 antagonists ondansetron and granisetron in feline ventricular myocytes.

    de Lorenzi, F G; Bridal, T R; Spinelli, W


    1. We investigated the effects of two 5-HT3 antagonists, ondansetron and granisetron, on the action potential duration (APD) and the delayed rectifier current (IK) of feline isolated ventricular myocytes. Whole-cell current and action potential recordings were performed at 37 degrees C with the patch clamp technique. 2. Ondansetron and granisetron blocked IK with a KD of 1.7 +/- 1.0 and 4.3 +/- 1.7 microM, respectively. At a higher concentration (30 microM), both drugs blocked the inward rect...

  1. Left ventricular hypertrophy and insulin resistance in adults from an urban community in The Gambia: cross-sectional study.

    Bernard Cudjoe Nkum

    Full Text Available OBJECTIVE: To determine the association between left ventricular hypertrophy and insulin resistance in Gambians. DESIGN: Cross-sectional study. SETTING: Outpatient clinics of Royal Victoria Teaching Hospital and Medical Research Council Laboratories in Banjul. PARTICIPANTS: Three hundred and sixteen consecutive patients were enrolled from outpatient clinics. The data of 275 participants (89 males were included in the analysis with a mean (± standard deviation age of 53.7 (±11.9 years. INTERVENTIONS: A questionnaire was filled and anthropometric measurements were taken. 2-D guided M-mode echocardiography, standard 12-1ead electrocardiogram, fasting insulin and the oral glucose tolerance test were performed. MAIN OUTCOME MEASURES: The Penn formula was used to determine the left ventricular mass index, 125 g/m2 in males and 110 g/m2 in females as the cut-off for left ventricular hypertrophy. Using the fasting insulin and fasting glucose levels, the insulin resistance was estimated by the homeostatic model assessment formula. Logistic regression analysis was used to determine the association between left ventricular hypertrophy and insulin resistance. RESULTS: The mean Penn left ventricular mass index was 119.5 (±54.3 and the prevalence of Penn left ventricular mass index left ventricular hypertrophy was 41%. The mean fasting glucose was 5.6 (±2.5 mmol/l, fasting insulin was 6.39 (±5.49 μU/ml and insulin resistance was 1.58 (±1.45. There was no association between Penn left ventricular mass index left ventricular hypertrophy and log of insulin resistance in univariate (OR = 0.98, 95% CI = 0.80-1.19, p = 0.819 and multivariate logistic regression (OR = 0.93, 95% CI = 0.76-1.15, p = 0.516 analysis. CONCLUSION: No association was found in this study between left ventricular hypertrophy and insulin resistance in Gambians and this does not support the suggestion that insulin is an independent determinant of left ventricular


    Mykytyuk, M R


    Examined 76 (26 men and 50 women) patients with active acromegaly aged 20 to 70 years, average age (48.22 ± 12.19). Echocardiographic signs of hypertrophy of the left ventricular (LVH) revealed by 63.2% of patients, including 46%--concentric LVH. Found that high levels of pituitary growth hormone (GH) and insulin like growth factor-1 (IGF-1) were independent predictors of LVH. Influence of GH and IGF-1 on the formation of LVH-mediated through anthropometric parameters and levels of systolic and diastolic blood pressure, which are predictors in patients with acromegaly LVH.

  3. Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

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


    BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two...... of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy......, potentially contributing to the reported adverse prognosis of metabolic syndrome....

  4. Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

    Zhe ZHANG; Hui-cai GUO; Li-nan ZHANG; Yong-li WANG


    Aim: The present study investigated the effect of adenosine on Na+-K+ pumps in acutely isolated guinea pig (C, avia sp.) ven-tricular myocytes.Methods: The whole-cell, patch-damp technique was used to record the Na+-K+ pump current (Ip) in acutely isolated guinea pig ventricular myocytes.Results: Adenosine inhibited the high DHO-affinity pump current (Ih) in a concentration-dependent manner, which was blocked by the selective adenosine A1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists stau-rosporine, GF 109203X or the specific δ isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A1 receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114. In contrast, the selec-tive A2A receptor agonist CGS21680 and A3 receptor agonist Cl-IB-MECA did not affect lb. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Further-more, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced Ih inhibition.Conclusion: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of Ih via adenosine A1 receptors and the PKC-δ isoform.

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

    Wachtell, Kristian; Palmieri, Vittorio; Gerdts, Eva;


    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...... 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...

  6. Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy

    Larstorp, Anne Cecilie K; Ariansen, Inger; Gjesdal, Knut


    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......, 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...

  7. Management implications of massive left ventricular hypertrophy in hypertrophic cardiomyopathy significantly underestimated by echocardiography but identified by cardiovascular magnetic resonance.

    Maron, Martin S; Lesser, John R; Maron, Barry J


    Cardiovascular magnetic resonance (CMR) is a high spatial resolution, 3-dimensional tomographic imaging technique which may identify regions of massive left ventricular hypertrophy (particularly when confined to the anterolateral free wall) in which the extent of wall thickness is underestimated with traditional 2-dimensional echocardiography in patients with hypertrophic cardiomyopathy (HC). This observation may have potential implications on management strategies as extreme left ventricular hypertrophy is a primary risk factor for sudden death in HC and therefore supports an expanding role for CMR in the evaluation of HC patients.

  8. Prevalencia de hipertrofia ventricular izquierda en pacientes diabéticos Prevalence of left ventricular hypertrophy in diabetic patients

    Diego Valarezo-Sevilla


    Full Text Available Con el objetivo de establecer la prevalencia de hipertrofia ventricular izquierda (HVI en pacientes con diabetes mellitus tipo 2 (DM, se realizó un estudio transversal en estos pacientes, estableciendo sus características antropométricas, presión arterial y control metabólico. Para evaluar la presencia de HVI se empleó ecocardiografía transtorácica. El estudio incluyó 91 pacientes, en los cuales la prevalencia de HVI fue de 63,7%, siendo más frecuente en mujeres que en varones (p=0,001. Adicionalmente, se encontró un 46,2% de pacientes con disfunción diastólica del ventrículo izquierdo. Se concluye que existe una importante prevalencia de HVI en pacientes diabéticos sin antecedentes de causas definidas de hipertrofia. No se encontró relación con sexo, control metabólico, IMC y tiempo de diagnósticoIn order to establish the prevalence of left ventricular hypertrophy (LVH in patients with type 2 diabetes mellitus, (DM a cross-sectional study was conducted in these patients studying their anthropometric characteristics, blood pressure and metabolic control. To evaluate the presence of LVH, a trans-thoracic echocardiogram was used. The study included 91 patients, finding a 63.7% prevalence of HVI, with women being more affected than men (p=0.001. Additionally, 46.2% of patients were found to have diastolic dysfunction of the left ventricle. We conclude that there is an important prevalence of LVH in diabetic patients without defined causes of hypertrophy. There was no association with sex, metabolic control, BMI and time of diagnosis

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

    Yoga Yuniadi


    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

  10. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease

    Nan Wu


    Full Text Available Aims. Left ventricular hypertrophy (LVH and albuminuria are both markers for cardiovascular diseases (CVDs in patients with type 2 diabetes mellitus (T2DM. We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; P<0.001. Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; P<0.001, age (P<0.001, systolic blood pressure (P=0.0578, and the use of ACEI/ARB drug (P<0.001 were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464 and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993 compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%, followed by eccentric hypertrophy (21.0%. Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD.

  11. Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy

    Bang, Casper N; Okin, Peter M; Køber, Lars


    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...... 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...

  12. Clinical value of regression of electrocardiographic left ventricular hypertrophy after aortic valve replacement.

    Yamabe, Sayuri; Dohi, Yoshihiro; Higashi, Akifumi; Kinoshita, Hiroki; Sada, Yoshiharu; Hidaka, Takayuki; Kurisu, Satoshi; Shiode, Nobuo; Kihara, Yasuki


    Electrocardiographic left ventricular hypertrophy (ECG-LVH) gradually regressed after aortic valve replacement (AVR) in patients with severe aortic stenosis. Sokolow-Lyon voltage (SV1 + RV5/6) is possibly the most widely used criterion for ECG-LVH. The aim of this study was to determine whether decrease in Sokolow-Lyon voltage reflects left ventricular reverse remodeling detected by echocardiography after AVR. Of 129 consecutive patients who underwent AVR for severe aortic stenosis, 38 patients with preoperative ECG-LVH, defined by SV1 + RV5/6 of ≥3.5 mV, were enrolled in this study. Electrocardiography and echocardiography were performed preoperatively and 1 year postoperatively. The patients were divided into ECG-LVH regression group (n = 19) and non-regression group (n = 19) according to the median value of the absolute regression in SV1 + RV5/6. Multivariate logistic regression analysis was performed to assess determinants of ECG-LVH regression among echocardiographic indices. ECG-LVH regression group showed significantly greater decrease in left ventricular mass index and left ventricular dimensions than Non-regression group. ECG-LVH regression was independently determined by decrease in the left ventricular mass index [odds ratio (OR) 1.28, 95 % confidence interval (CI) 1.03-1.69, p = 0.048], left ventricular end-diastolic dimension (OR 1.18, 95 % CI 1.03-1.41, p = 0.014), and left ventricular end-systolic dimension (OR 1.24, 95 % CI 1.06-1.52, p = 0.0047). ECG-LVH regression could be a marker of the effect of AVR on both reducing the left ventricular mass index and left ventricular dimensions. The effect of AVR on reverse remodeling can be estimated, at least in part, by regression of ECG-LVH.

  13. [Left-ventricular hypertrophy as a cardiac risk factor: role of the renin-angiotensin-aldosterone system].

    Erne, P


    Left-ventricular hypertrophy is the result of cardiac adaptation to global or regional overstress and represents an important cardiovascular risk factor, increasing the risk for development of congestive heart failure and incidence of sudden death. This review describes the pathophysiological and biochemical mechanisms involved in the development of left-ventricular hypertrophy and cardiac fibrosis with particular emphasis on the role of angiotensin II and aldosterone. Central to the cascade of cardiac fibrosis is the increased production or reduced degradation of collagen proteins in fibroblasts. Collagen proteins are proteins needed for the alignment of cellular compartments and the development of forces, contraction and relaxation of the heart. If overexpressed, an important rise of wall stiffness is observed in addition to a reduced capacity to provide oxygen to the cardiac tissue. This latter explains why in areas of histologically hypertrophied heart muscle atrophied muscle cells are observed. The characterization of the second-messenger systems involved in the regulation of cardiac cells as well as the identification of angiotensin-II receptor subtype and angiotensin IV is described. Both of these receptors are present on cardiac fibroblasts and stimulate these to collagen production, which can be inhibited by antagonists or the generation of angiotensin II by ACE inhibitors. In some forms of left-ventricular hypertrophy and in patients with congestive heart failure in addition to elevated angiotensin-II levels, increased aldosterone levels are observed. Aldosterone raises upon stimulation by angiotensin II and upon reduction of angiotensin-II generation subsequent to ACE inhibition through an escape mechanism. The contribution of aldosterone to left-ventricular hypertrophy and cardiac fibrosis can be prevented and reduced by the administration of its antagonist, spironolactone. Further and larger clinical trials are needed and in progress to evaluate if the

  14. Calcium release near l-type calcium channels promotes beat-to-beat variability in ventricular myocytes from the chronic AV block dog

    Antoons, G.; Johnson, Daniel M; Dries, Eef; Santiago, Demetrio J; Ozdemir, Semir; Lenaerts, Ilse; Beekman, Jet D M; Houtman, Marien J C; Sipido, Karin R; Vos, Marc A


    Beat-to-beat variability of ventricular repolarization (BVR) has been proposed as a strong predictor of Torsades de Pointes (TdP). BVR is also observed at the myocyte level, and a number of studies have shown the importance of calcium handling in influencing this parameter. The chronic AV block (CAV

  15. Serum cystatin C concentration as an independent marker for hypertensive left ventricular hypertrophy

    Xin Li; Hang Zhu; Peng Li; Qian Xin; Jie Liu; Wei Zhang; You-Hong Xing; Hao Xue


    Background Serum cystatin C levels can be used to predict morbidity and mortality in patients with cardiovascular disease. However, the clinical relevance of serum cystatin C levels in patients with hypertensive left ventricular hypertrophy (LVH) has rarely been investigated. We designed the present study to investigate whether serum cystatin C levels are associated with cardiac structural and functional alterations in hypertensive patients. Methods We enrolled 823 hypertensive patients and classified them into two groups:those with LVH (n=287) and those without LVH (n=536). All patients underwent echocardiography and serum cystatin C testing. We analyzed the relationship be-tween serum cystatin C levels and LVH. Results Serum cystatin C levels were higher in hypertensive patients with LVH than in those without LVH (P<0.05). Using linear correlation analysis, we found a positive correlation between serum cystatin C levels and interven-tricular septal thickness (r=0.247, P<0.01), posterior wall thickness (r=0.216, P<0.01), and left ventricular weight index (r=0.347, P<0.01). When analyzed by multiple linear regression, the positive correlations remained between serum cystatin C and interventricular septal thickness (β=0.167, P<0.05), posterior wall thickness (β=0.187, P<0.05), and left ventricular weight index (β=0.245, P<0.01). Con-clusion Serum cystatin C concentration is an independent marker for hypertensive LVH.

  16. Decreases of voltage-dependent K+ currents densities in ventricular myocytes of guinea pigs by chronic oxidant stress

    De-li DONG; Yan LIU; Yu-hong ZHOU; Wei-hua SONG; He WANG; Bao-feng YANG


    AIM: To determine the changes of delayed rectifier K+ currents (Ik) and inward rectifier K+ currents (Ik1) in the ventricular myocytes of guinea pigs during the gradual apoptotic process by the chronic oxidant stress treatment.METHODS: H2O250 μmol/L (24 h) was used for inducing apoptosis in the cardiomyocytes culture of neonatal rats and to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by TUNEL methods and voltage-dependent K+ currents were recorded by patch-clamp techniques. RESULTS: H2O250 μmol/L (24 h) induced cell apoptosis in the cardiomyocytes culture of neonatal rats. This concentration was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the voltage-dependent K+currents densities (Ik, Ik1) were down-regulated. The densities of the delayed rectifier K+ currents (Ik) in 50 μmol/L H2O2 group were 2.52±0.57 pA/pF vs 5.73±1.84 pA/pF in the control group at +50 mV (n=8, P<0.01). The densities of the inward rectifier K+ currents (Ik1) in 50 μmol/L H2O2 group were -13.9±2.70 pA/pF, 2.52±0.57 pA/pF vs -59.7± 11.9 pA/pF, 5.73± 1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and -40 mV (n=8, P<0.05), respectively. The extent of inward rectifier property of Ik1 was weakened by 50μmol/L H2O2 treatment. CONCLUSION: The densities of Ik, Ik1 in the cardiomyocytes of guinea pigs were downregulated and the inward rectifier property of Ik1 was weakened during the gradual apoptotic process after 50 μmol/L H2O2 treatment for 24 h.

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

    Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi


    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...

  18. Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

    XUE Hao; WANG Shu-xia; WANG Xiao-jian; XIN Ying; WANG Hu; SONG Xiao-dong; SUN Kai; WANG Yi-bo; HUI Ru-tai


    Background Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.Methods Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n=2120 and n=324).Results We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI))0.58 (0.358-0.863), P=0.035; OR (95% CI)=0.477 (0.225-0.815), P<0.05,respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P<0.01).Conclusion These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

  19. Positron emission tomographic evaluation of regulation of myocardial perfusion in physiological (elite athletes) and pathological (systemic hypertension) left ventricular hypertrophy

    Kjaer, Andreas; Meyer, Christian; Wachtell, Kristian


    Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age-match...

  20. [An unusual case of transient ST-segment elevation during hypertensive crisis in a patient with left ventricular hypertrophy].

    Cappelletti, Alberto; Maggio, Silvia; Maranta, Francesco; Mazzavillani, Monica; Margonato, Alberto; Camici, Paolo G


    We report the case of a 73-year-old patient with severe left ventricular hypertrophy presenting with acute ST-segment elevation mimicking acute myocardial infarction on ECG during a hypertensive crisis. Unexpectedly, emergency coronary angiography showed no evidence of coronary thrombosis or spasm. Electrocardiographic alterations gradually resolved after lowering blood pressure.

  1. Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats.

    Zhang, Cheng-Xi; Pan, Si-Nian; Meng, Rong-Sen; Peng, Chao-Quan; Xiong, Zhao-Jun; Chen, Bao-Lin; Chen, Guang-Qin; Yao, Feng-Juan; Chen, Yi-Li; Ma, Yue-Dong; Dong, Yu-Gang


    1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent studies suggest that pharmacological activation of AMPK inhibits cardiac hypertrophy. In the present study, we examined whether long-term treatment with metformin could attenuate ventricular hypertrophy in a rat model. The potential involvement of nitric oxide (NO) in the effects of metformin was also investigated. 2. Ventricular hypertrophy was established in rats by transaortic constriction (TAC). Starting 1 week after the TAC procedure, rats were treated with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were used to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10⁻⁶ mol/L) for 24 h under serum-free conditions in the presence or absence of metformin (10⁻³ mol/L), compound C (10⁻⁶ mol/L), L-NAME (10⁻⁶ mol/L) or their combination. The rate of incorporation of [³H]-leucine was determined, western blotting analyses of AMPK-eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were undertaken and the concentration of NO in culture media was determined. 4. Transaortic constriction resulted in significant haemodynamic dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident. Treatment with metformin improved haemodynamic function and significantly attenuated ventricular hypertrophy. Most of the effects of metformin were abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on haemodynamic function and ventricular hypertrophy in TAC rats. 5. In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME. The improvement in cardiac structure and

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

    Buxton, I.L.O.; Brunton, L.L.


    When incubated with purified cardiomyocytes from adult rat ventricle, the 1-antagonist (TH)prazosin binds to a single class of sites with high affinity. Competition for (TH)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 (TH)yohimbine results in no measurable specific binding. Agonist competition for (TH)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 (TH)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 W 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 the US -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.

  3. Correlation Study of PtfV1 with Heart-Qi Deficiency Syndrome in Patients with Hypertensive Left Ventricular Hypertrophy

    杨传华; 陆峰


    @@ It is generally believed that the change of p-wave terminal force in lead V1 (PtfV1) is associated with the inner diameter of left atrium, left ventricular compliance,and ventricular diastolic function. The increase of negative value of PtfV1 in essential hypertensive (EH) patients with left ventricular hypertrophy (LVH) indicates the cardiac function may be damaged. In order to explore the relationship between Heart-Qi Deficiency Syndrome (HQDS) of TCM and PtfV1 level in hypertensive LVH patients, correlation analysis of scores of Heart-Qi Deficiency Syndrome and negative value of PtfV1 was made by the authors.

  4. Nanoscale distribution of ryanodine receptors and caveolin-3 in mouse ventricular myocytes: dilation of t-tubules near junctions.

    Wong, Joseph; Baddeley, David; Bushong, Eric A; Yu, Zeyun; Ellisman, Mark H; Hoshijima, Masahiko; Soeller, Christian


    We conducted super-resolution light microscopy (LM) imaging of the distribution of ryanodine receptors (RyRs) and caveolin-3 (CAV3) in mouse ventricular myocytes. Quantitative analysis of data at the surface sarcolemma showed that 4.8% of RyR labeling colocalized with CAV3 whereas 3.5% of CAV3 was in areas with RyR labeling. These values increased to 9.2 and 9.0%, respectively, in the interior of myocytes where CAV3 was widely expressed in the t-system but reduced in regions associated with junctional couplings. Electron microscopic (EM) tomography independently showed only few couplings with caveolae and little evidence for caveolar shapes on the t-system. Unexpectedly, both super-resolution LM and three-dimensional EM data (including serial block-face scanning EM) revealed significant increases in local t-system diameters in many regions associated with junctions. We suggest that this regional specialization helps reduce ionic accumulation and depletion in t-system lumen during excitation-contraction coupling to ensure effective local Ca²⁺ release. Our data demonstrate that super-resolution LM and volume EM techniques complementarily enhance information on subcellular structure at the nanoscale.

  5. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C;


    with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8...... mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged......The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...

  6. Transcriptional network analysis for the regulation of left ventricular hypertrophy and microvascular remodeling.

    Moreno-Moral, Aida; Mancini, Massimiliano; D'Amati, Giulia; Camici, Paolo; Petretto, Enrico


    Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.

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

    Tillmanns Harald H


    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 α-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.

  8. Cardiac morphology in left ventricular hypertrophy using thallium-201 myocardial scintigraphy

    Torii, Yukio; Adachi, Haruhiko; Katsume, Hiroshi; Ochiai, Masakazu; Ijichi, Hamao


    To evaluate cardiac morphology in the patients with various cases of hypertrophy, we measured left ventricular (LV) size using thallium-201 myocardial scintigraphy in 29 normal subjects and in 90 patients. Cardiac shape and dimension were assessed by measuring the wall thickness and external length in the short and long axis of LV image in LAO projection. In aortic stenosis and hypertensive heart disease the shape was spherical and the wall was thickened. In both mitral (MR) and aortic (AR) regurgitations, LV dilatation were shown; spherical shape in chronic MR but ellipsoid shape in acute MR and AR. Decreased LV size but normal shape was observed in mitral stenosis and cor pulmonale. In hypertrophic cardiomyopathy the LV wall was asymmetrically hypertrophied, while in congestive cardiomyopathy the wall is thin with marked LV dilatation and the shape was spherical. We concluded that the heart had characteristic configuration which might reflect cardiac performance or compensate for the load to the heart, and that thallium-201 myocardial scintigraphy is useful in the evaluation of cardiac morphology as well as in diagnosis of myocardial ischemia. (author).

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

    Elena Ulasova


    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.

  10. Effects of Ginkgolide B on action potential and calcium,potassium current in guinea pig ventricular myocytes

    Xiao-yan QI; Zhi-xiong ZHANG; You-qiu XU


    AIM: To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (ICa-L) in guinea pig ventricular myocytes. METHODS: Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, ICa-L were recorded by whole-cell patch-clamp technique in either current or voltage clamp mode. RESULTS: GB shortened APD in a concentration-dependent manner. GB 0.1, 1, and 10 μmol/L shortened APD50 by 7.9 % (n=5, P>0.05), 18.4 % (n=5, P<0.01), and 28.9 % (n=6, P<0.01), respectively; APD90 by 12.4 % (n=5, P>0.05), 17.6 % (n=5, P<0.01), 26.4 % (n=5, P<0.01),respectively. GB increased IK in a concentration-dependent manner. GB 0.1, 1, and l0 μmol/L increased IK by 20.1% (n=6, P<0.05), 43.1% (n=6, P<0.01), 55.6 % (n=6, P<0.05); increased IKtail by 10.7 % (n=6, P<0.05),25.1% (n=6, P<0.05), and 37.7 % (n=6, P<0.05), respectively at testing potential of +50 mV and shift the I-V curve of Ik upward. But GB had no significant effect on ICa-L at above concentrations. CONCLUSION: GB significantly shortened APD in a concentration-dependent manner which mainly due to increase of IK.

  11. Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes

    Xiong WANG; Bo-wei WU; Dong-mei WU


    Aim: To compare the effects of AMP579 and adenosine on L-type Ca2+ current (ICa- L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on ICa-L. Methods: ICa-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10 nmol/L to 50 μmol/L) showed no effect on basal ICa- L, but it inhibited the ICa-L induced by isoproterenol 10 nmol/L in a concen tration-dependent manner with the IC50 of 13.06 μmol/L. Similar to adenosine,AMP579 also showed an inhibitory effect on the ICa-L induced by isoproterenol.AMP579 and adenosine (both in 10 μmol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal ICa-L in a concentration-dependent manner with IC50 (1.17 μmol/L).PD116948 (30 μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal ICa-L. However, GF109203X (0.4 μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal ICa-L. So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A1 receptor. Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the ICa-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal ICa-L at downstream-mechanism.

  12. Effects of β2-Adrenergic Antagonist on Cytosolic Ca2+ in Ventricular Myocytes from Infarcted Rat Heart

    Yang Hui; Wu Wei; Zeng Chong; Deng Chunyu; Fang Chang; Chen Shanming


    Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca2 +([Ca2+]i) in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated.Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction (MI) and [Ca2+]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absenceof beta1-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1,2- adrenergic antagonists propranolol was examined.Results The followings were found that ICI11 8, 551 had no significant effects on the rise of [Ca2+]i induced by isoproterenol in normal ventricular myocytes (P >0.05), ICI118, 551 only significantly attenuated the rise of [Ca2+]i induced by isoproterenol at four weeks and eight weeks after MI (24.5% ±5.7% vs 57.8% ±13.2%, P< 0.01; 12.2%±7.9% vs 44.6%±11.3%, P<0.01). Atenolol had suppressive effects only in the control group and the post-MI group of two weeks (P<0.05), and propranolol had suppressive effects in the control and all the three post-MI groups (P<0.01).Conclusions Beta2-adrenergic antagonist ICI118,551 may exert negative effects on Ca2+ overload initiated by sympathetic stimulation after MI.

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

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


    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.

  14. Azimilide causes reverse rate-dependent block while reducing both components of delayed-rectifier current in canine ventricular myocytes.

    Gintant, G A


    Most class III antiarrhythmic drugs reduce the rapidly activating component of delayed-rectifier current (IKr) without affecting the slowly activating component (IKs). Recently the novel antiarrhythmic agent azimilide (NE-10064) was reported to enhance IKs at low (nanomolar) concentrations and to block both IKr and IKs at higher (micromolar) concentrations. Further to understand the electrophysiologic effects of azimilide, we compared its effects on IKr and IKs (by using whole cell clamp techniques) and action potentials (microelectrode and perforated-patch techniques) on canine ventricular myocytes. A lower azimilide concentration (50 nM) did not enhance IKs. In contrast, a therapeutic azimilide concentration (2 microM) was equieffective in reducing IKr (300-ms isochrones) and IKs (3-s isochrones) by approximately 40% during depolarizing test pulses, as well as reducing IKr (38% decrease) and IKs (33% decrease) tail currents on repolarization. Block of IKs was independent of voltage at positive test potentials. In action-potential studies, 50 nM azimilide had no effect on the action-potential duration (APD), whereas 2 microM azimilide delayed repolarization and caused reverse rate-dependent effects on the APD. Whereas the extent of APD prolongation by azimilide was not correlated with the drug-free APD, azimilide preferentially exaggerated the APD-rate relationship of myocytes displaying the steepest APD-rate relationship under drug-free conditions. In conclusion, therapeutic concentrations of azimilide that cause comparable reduction of canine ventricular IKr and IKs exert reverse rate-dependent effects, which are dependent on the steepness of the APD-rate relationship.

  15. Effects of the venom of the spider Ornithoctonus hainana on neonatal rat ventricular myocytes cellular and ionic electrophysiology.

    Zhang, Yiya; Liu, Jinyan; Liu, Zhonghua; Wang, Meichi; Wang, Jing; Lu, Shanshan; Zhu, Li; Zeng, Xiongzhi; Liang, Songping


    Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with specific pharmacological properties. However, few peptides from spider venoms were detected as cardiac channel antagonists. In order to explore the effects of the venom of Ornithoctonus hainana on the action potential and ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch clamp technique was used to record action potential duration (APD), sodium current (INa), L calcium current (ICaL), rapidly activating and inactivating transient outward currents (Ito1), rapid (IKr) and slow (IKs) components of the delayed rectifier currents and the inward rectifier currents (IK1). Our results showed that 100 μg/mL venom obviously prolonged APDs. Significantly, the venom could inhibit INa and ICaL effectively, while no evident inhibitory effects on cardiac K(+) channels (Ito1, Iks, Ikr and Ik1) were observed, suggesting that the venom represented a multifaceted pharmacological profile. The effect of venom on Na(+) and Ca(2+) currents of ventricular myocytes revealed that the hainan venom as a rich resource of cardiac channel antagonists might be valuable tools for the investigation of both channels and drug development.

  16. Cardiac output and associated left ventricular hypertrophy in pediatric chronic kidney disease.

    Weaver, Donald J; Kimball, Thomas R; Koury, Phillip R; Mitsnefes, Mark M


    A significant number of children with chronic kidney disease (CKD) have eccentric left ventricular hypertrophy (LVH), suggesting the role of preload overload. Therefore, we hypothesized that increased cardiac output (CO) might be a contributing factor for increased left ventricular mass index (LVMI) in these children. Patients aged 6-20 years with CKD stages 2-4 were enrolled. Echocardiograms were performed to assess LV function and geometry at rest and during exercise. Heart rate, stroke volume, and CO were also assessed at rest and during exercise. Twenty-four-hour ambulatory blood pressure (AMBP) monitoring was performed. Of the patients enrolled in this study, 17% had LVH. Increased stroke volume and CO were observed in patients with LVH compared to patients without LVH. Univariate analysis revealed significant positive associations between LVMI and CO, stroke volume, body mass index, pulse pressure from mean 24-h AMBP, and mean 24-h systolic BP load. No association with heart rate, age, parathyroid hormone, glomerular filtration rate, or anemia was observed. Only CO (beta = 1.98, p = 0.0005) was independently associated with increased LVMI in multivariate modeling (model R (2) = 0.25). The results of this study suggest that increased CO might predispose to increased LVMI in pediatric patients with CKD. Adaptations may be required to meet increased metabolic demand in these patients.

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

    Randon R.B.


    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.

  18. Modeling and visualization of the activation wavefront propagation to improve understanding the QRS complex changes indicating left ventricular hypertrophy.

    Svehlikova, Jana; Zelinka, Jan; Bacharova, Ljuba; Tysler, Milan


    Activation wavefront propagation was computed and visualized in a geometrical heart model for pathological cases of reduced velocity of propagation, left ventricular hypertrophy and their combination. Selected parameters of a multiple dipole equivalent heart generator were computed and compared for three heart geometries and several degrees and extents of reduction of propagation velocity. First, the influence of geometrical changes modeling the left ventricular hypertrophy at reference propagation velocity was compared with reduction of the propagation velocity in the reference heart geometry. Reduced propagation velocity yielded similar or greater changes of the magnitude of the (electrical) heart vector representing the activation wavefront than the geometrical changes. Observations of the wavefront propagation with reduced velocity revealed longer presence of a large extent of the wavefront during depolarization which resulted in increased magnitude of the heart vector. The duration of depolarization was significantly prolonged only when the propagation velocity was decreased to 25% of its normal value. Changes of the direction of the maximal heart vector were dependent on the position of the region where the propagation velocity was reduced. Then the combination of the left ventricular hypertrophy and reduced propagation velocity was studied. Such combination enhanced the enlargement of the electrical heart vector and significantly prolonged the duration of depolarization. The influence of reduced activation velocity on the observed parameters was greater than the effect of the enlargement of the left ventricular mass. The presented study showed that intramyocardial conduction disturbances might cause increase of the actual surface area of propagation wavefront leading to changes of the amplitudes of ECG signals comparable with the changes resulting from the left ventricular hypertrophy. Intramyocardial conduction disturbances, as well as the modeled 50

  19. Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

    Shu-ichi Fujita

    Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

  20. Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes.

    Kistamas, K; Szentandrassy, N; Hegyi, B; Vaczi, K; Ruzsnavszky, F; Horvath, B; Banyasz, T; Nanasi, P P; Magyar, J


    The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 μM) decreased, while Ca(2+) ionophore A23187 (1 μM) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 μM ryanodine and 1 μM cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 μM SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect.

  1. [Left ventricular function in hypertension without left ventricular hypertrophy: echographic study with modelisation of left ventricular-aortic coupling].

    Bonnet, B; Jourdan, F; du Cailar, G; Mimran, A; Fesler, P


    Because the functional interaction between the LV and arterial systems, termed ventricular-arterial coupling, is recognized as a key determinant of LV performance, the objective of the present study was to assess the impact of uncomplicated HT without LVH on LV performance using simultaneously echocardiography and carotid tonometry. LV maximal power (PmaxVG), cardiac power output (CPO), LV efficiency (CPO/PmaxVG), input aortic and output LV elastance (Ea and Ees) were assessed in 20 normotensive control subjects (NT) and 10 patients with untreated HT. PmaxVG was calculated according to the integral of the product of LV wall stress with strain rate (as an index of gradient velocity). Cyclic variation of wall thickness and SR were measured by speckel-tracking. Ea and Ees were derived and modelized from the pressure-volume curve. No difference in age, BMI and sex ratio was observed between NT and HT. Systolic BP (160±18 vs. 119±10mmHg), LV mass (99±15 vs. 76±12g/m(2)), PWV (9.7±2 vs. 6.9±1m/s) were significantly higher (P<0.01) in HT when compared to NT. In HT increased of CPO and Ea was compensated by an increase of LV (15±4 vs. 12±3%, P<0.02) and Ees (5.5±2 vs. 4.5±1.5mmHg/mL), which are significantly elevated in HT (P<0.05). No difference was observed in Ea/Ees between NT and HT. In conclusion at the early phase of HT, in patients without LVH, LV performance and ventricular-arterial coupling were adapted to post-load elevation. This adaptation may be the result of an increased of LV contractility.

  2. Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

    Nayak, Alok Ranjan; Shajahan, T K; Panfilov, A V; Pandit, Rahul


    Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac

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

    Michael eNivala


    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.

  4. Role of SERCA and the sarcoplasmic reticulum calcium content on calcium waves propagation in rat ventricular myocytes.

    Salazar-Cantú, Ayleen; Pérez-Treviño, Perla; Montalvo-Parra, Dolores; Balderas-Villalobos, Jaime; Gómez-Víquez, Norma L; García, Noemí; Altamirano, Julio


    In Ca(2+)-overloaded ventricular myocytes, SERCA is crucial to steadily achieve the critical sarcoplasmic reticulum (SR) Ca(2+) level to trigger and sustain Ca(2+) waves, that propagate at constant rate (ʋwave). High luminal Ca(2+) sensitizes RyR2, thereby increasing Ca(2+) sparks frequency, and the larger RyR2-mediated SR Ca(2+) flux (dF/dt) sequentially activates adjacent RyR2 clusters. Recently, it was proposed that rapid SERCA Ca(2+) reuptake, ahead of the wave front, further sensitizes RyR2, increasing ʋwave. Nevertheless, this is controversial because rapid cytosolic Ca(2+) removal could instead impair RyR2 activation. We assessed whether rapid SR Ca(2+) uptake enhances ʋwave by changing SERCA activity (ҡDecay) over a large range (∼175%). We used normal (Ctrl) and hyperthyroid rat (HT; reduced phospholamban by ∼80%) myocytes treated with thapsigargin or isoproterenol (ISO). We found that ʋwave and dF/dt had a non-linear dependency with ҡDecay, while Ca(2+) waves amplitude was largely unaffected. Furthermore, SR Ca(2+) also showed a non-linear dependency with ҡDecay, however, the relationships ʋwave vs. SR Ca(2+) and ʋwave vs. dF/dt were linear, suggesting that high steady state SR Ca(2+) determines ʋwave, while rapid SERCA Ca(2+) uptake does not. Finally, ISO did not increase ʋwave in HT cells, therefore, ISO-enhanced ʋwave in Ctrl depended on high SR Ca(2+).

  5. Mitogen-activated protein kinase signal pathways play an important role in right ventricular hypertrophy of tetralogy of Fallot

    ZHANG Hong-shan; WU Qing-yu; XU Ming; ZHOU Yu-xiang; SHUI Chao-xiang


    Background Tetralogy of Fallot (TOF) is the most common malformation of children with an incidence of approximately 10% of congenital heart disease patients.There can be a wide spectrum to the severity of the anatomic defects,which include ventricular septal defect,aortic override,right ventricular outflow tract obstruction,and right ventricular hypertrophy.We examined the relationship between right ventricular hypertrophy in patients with TOF and the gene expression of factors in the mitogen-activated protein kinase (MAPK) signal pathway.Methods To gain insight into the characteristic gene(s) involved in molecular mechanisms of right ventricular hypertrophy in TOF,differential mRNA and micro RNA expression profiles were assessed using expression-based micro array technology on right ventricular biopsies from young TOF patients who underwent primary correction and on normal heart tissue.We then analyzed the gene expression of the MAPK signal pathway using reverse transcription-polymerase chain reaction (RT-PCR) in normals and TOF patients.Results Using the micro RNA chip V3.0 and human whole genome oligonucleotide microarray V1.0 to detect the gene expression,we found 1068 genes showing altered expression of at least two-fold in TOF patients compared to the normal hearts,and 47 micro RNAs that showed a significant difference of at least two-fold in TOF patients.We then analyzed these mRNAs and micro RNAs by target gene predicting software Microcosm Targets version 5.0,and determined those mRNA highly relevant to the right ventricular hypertrophy by RT-PCR method.There were obvious differences in the gene expression of factors in the MAPK signal pathway when using RT-PCR,which was consistent to the results of the cDNA microarray.Conclusion The upregulation of genes in the MAPK signal pathway may be the key events that contribute to right ventricular hypertroohv and stunted angiogenesis in patients with TOF.

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

    Diederichsen, Søren Zöga; Gerke, Oke; Olsen, Michael Hecht


    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...

  7. Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study

    Larstorp, A C K; Okin, P M; Devereux, R B;


    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 losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point...

  8. Barnidipine or Lercanidipine on Echocardiographic Parameters in Hypertensive, Type 2 Diabetics with Left Ventricular Hypertrophy: A Randomized Clinical Trial

    Giuseppe Derosa; Amedeo Mugellini; Fabrizio Querci; Ivano Franzetti; Rosa Maria Pesce; Angela D’Angelo; Pamela Maffioli


    The aim of this study was to evaluate the effects of lercanidipine or barnidipine on echocardiographic parameters, in hypertensive, type 2 diabetics with left ventricular hypertrophy. One hundred and forty-four patients were randomized to lercanidipine, 20 mg/day, or barnidipine, 20 mg/day, in addition to losartan, 100 mg/day, for 6 months. We evaluated: blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid profile, creatinine, estimated glomerular filtration rate (...

  9. Enhancement of contraction and L-type Ca(2+) current by murrayafoline-A via protein kinase C in rat ventricular myocytes.

    Chidipi, Bojjibabu; Son, Min-Jeong; Kim, Joon-Chul; Lee, Jeong Hyun; Toan, Tran Quoc; Cuong, Nguyen Manh; Lee, Byung Ho; Woo, Sun-Hee


    We previously reported that murrayafoline-A (1-methoxy-3-methyl-9H-carbazole, Mu-A) increases the contractility of ventricular myocytes, in part, via enhancing Ca(2+) influx through L-type Ca(2+) channels, and that it increases the Ca(2+) transients by activation of protein kinase C (PKC). In the present study, we further examined the cellular mechanisms for the enhancement of contractility and L-type Ca(2+) current (ICa,L) by Mu-A. Cell shortening and ICa,L were measured in rat ventricular myocytes using a video edge detection method and perforated patch-clamp technique, respectively. We found that the positive inotropic effect of Mu-A was not affected by pre-exposure to the β-adrenoceptor antagonist propranolol, the protein kinase A (PKA) inhibitors KT5720 or H-89, or the phospholipase C inhibitor U73122. Interestingly, the Mu-A-mediated increases in cell shortening and in the rate of contraction were completely suppressed by pre-treatment with the PKC inhibitor GF109203X. The stimulatory effect of Mu-A on ICa,L was not altered by inhibition of PKA (KT5720), G-protein coupled receptors (suramin), or α1-adrenoceptor (prazosin). However, pre-exposure to the PKC inhibitor, GF109203X or chelerythrine, abolished the Mu-A-induced increase in ICa,L. Pre-exposure to the Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 slightly reduced the stimulatory effects on contraction and ICa,L by Mu-A. Phosphorylation of PKC was enhanced by Mu-A in ventricular myocytes. These data suggest that Mu-A increases contraction and ICa,L via PKC in rat ventricular myocytes, and that the PKC-mediated responses in the presence of Mu-A may be partly mediated by CaMKII.

  10. Sophocarpine attenuates the Na(+)-dependent Ca2(+) overload induced by Anemonia sulcata toxin-increased late sodium current in rabbit ventricular myocytes.

    Zhang, Shuo; Ma, Ji-Hua; Zhang, Pei-Hua; Luo, An-Tao; Ren, Zhi-Qiang; Kong, Ling-Hao


    Many studies indicate that an increase in late sodium current (I(Na.L)) of cardiomyocytes causes intracellular Na overload and subsequently raises the reverse Na/Ca exchanger current (INCX), ultimately resulting in intracellular Ca overload. Therefore, using drugs to inhibit the increased INa.L under various pathological conditions can lower intracellular Ca overload. This study was intended to explore the effect of sophocarpine (SOP) on the increase in INa.L, INCX, calcium transient and contraction in rabbit ventricular myocytes induced by Anemonia sulcata toxin II (ATX II), an opener of sodium channel, with the application of whole-cell patch-clamp techniques, the video-based motion edge detection system, and the intracellular calcium concentration determination system. The results indicate that tetrodotoxin (TTX, 4 μM ) obviously decreased INa.L and INCX enlarged by ATX II (30 nM), and SOP (20, 40, and 80 μM) also inhibited both the parameters concentration dependently in rabbit ventricular myocytes. However, transient sodium current remained unaffected by the above-mentioned concentrations of ATX II, TTX, and SOP. In addition, SOP also reversed diastolic calcium concentration, calcium transient amplitude, and ventricular muscle contractility augmented by ATX II. Its effects were similar to those of TTX, a specific inhibitor of the sodium channel. In conclusion, SOP inhibits INa.L, INCX, diastolic Ca concentration, and contractility in rabbit ventricular myocytes, which suggests that relief of intracellular Ca overload through inhibiting INa.L is likely to become a new therapeutic mechanism of SOP against arrhythmia and myocyte damage associated with intracellular Ca overload.


    E. I. Tarlovskaya


    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.

  12. The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy

    Guo, Xiying; Fan, Chaomei; Tian, Lei; Zhang, Xiuling; Zhao, Xing; Wang, Fengqi; Zhu, Hongguang; Lin, Aiqing; Wu, Xia; Li, Yishi


    Introduction Severe right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH. Methods HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared. Results Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients. Conclusions HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations. PMID:28323875

  13. Effects of Simvastatin on Ion Channel Currents in Ventricular Myocytes from Acute Infarcted Heart of Normocholesterolemic Rabbits

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang


    Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rab-bit heart suffering from acute myocardial infarction (AMI), so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups: AMI group, simv-astatin intervention group (Statin group) and sham-operated control group (CON). Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg-1 · d-1 (Statin group) or placebo (AMI group) for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, inclu-ding sodium current (Ina), L-type calcium current (Ica-L) and transient outward potassium current (Ito). Results ① There was not significant difference in serum cholesterol concentration among three groups. ② The peak Ina current den-sity (at -30 mV) was significantly decreased in AMI group (-25.26±5. 28, n = 13), comparing with CON (-42. 78±5.48, n = 16), P < 0. 05, while it was significantly increased in Statin group (-39. 83±5. 65 pA/pF, n = 12) comparing with AMI group, P <0. 01; The peak I Ca-L current density (at 0 mV) was significantly decreased in AMI group (- 3.43±0. 92 pA/pF, n = 13) comparing with CON (- 4. 56±1.01 pA/pF, n = 15), P < 0. 05, while it was significantly increased in Statin group (-4. 18±0. 96 pA/pF, n = 12) comparing with AMI group, P <0. 05; The Ito current density (at + 60 mV) was significantly decreased in AMI group (11.41±1.94 pA/pF, n = 13) compa-ring with CON (17. 41±3. 13 pA/pF, n = 15), P <0. 01, while it was significantly increased in Statin group (16. 11±2. 43 pA/pF, n = 14) comparing with AMI group, P < 0. 01. Conclusions AMI induces significant down-regula-tion of Ina, I Ca-L and Ito. Pretreatment with

  14. Effect of exercise training on Ca{sup 2+} release units of left ventricular myocytes of spontaneously hypertensive rats

    Carneiro-Júnior, M.A. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Amadeu, M.A.; Oliveira, E.M. [Universidade de São Paulo, Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de Educação Física e Esportes, São Paulo, SP (Brazil); Felix, L.B. [Universidade Federal de Viçosa, Departamento de Engenharia Elétrica, Viçosa, MG (Brazil); Cruz, J.S. [Universidade Federal de Minas Gerais, Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Belo Horizonte, MG (Brazil); Mill, J.G. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Natali, A.J.; Prímola-Gomes, T.N. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil)


    In cardiomyocytes, calcium (Ca{sup 2+}) release units comprise clusters of intracellular Ca{sup 2+} 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 training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca{sup 2+} 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 Ca{sup 2+} 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 ΔF/F{sub 0}), 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 Ca{sup 2+} sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F{sub 0}, 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

  15. AKAP150 participates in calcineurin/NFAT activation during the down-regulation of voltage-gated K(+) currents in ventricular myocytes following myocardial infarction.

    Nieves-Cintrón, Madeline; Hirenallur-Shanthappa, Dinesh; Nygren, Patrick J; Hinke, Simon A; Dell'Acqua, Mark L; Langeberg, Lorene K; Navedo, Manuel; Santana, Luis F; Scott, John D


    The Ca(2+)-responsive phosphatase calcineurin/protein phosphatase 2B dephosphorylates the transcription factor NFATc3. In the myocardium activation of NFATc3 down-regulates the expression of voltage-gated K(+) (Kv) channels after myocardial infarction (MI). This prolongs action potential duration and increases the probability of arrhythmias. Although recent studies infer that calcineurin is activated by local and transient Ca(2+) signals the molecular mechanism that underlies the process is unclear in ventricular myocytes. Here we test the hypothesis that sequestering of calcineurin to the sarcolemma of ventricular myocytes by the anchoring protein AKAP150 is required for acute activation of NFATc3 and the concomitant down-regulation of Kv channels following MI. Biochemical and cell based measurements resolve that approximately 0.2% of the total calcineurin activity in cardiomyocytes is associated with AKAP150. Electrophysiological analyses establish that formation of this AKAP150-calcineurin signaling dyad is essential for the activation of the phosphatase and the subsequent down-regulation of Kv channel currents following MI. Thus AKAP150-mediated targeting of calcineurin to sarcolemmal micro-domains in ventricular myocytes contributes to the local and acute gene remodeling events that lead to the down-regulation of Kv currents.

  16. Intraspecific scaling laws are preserved in ventricular hypertrophy but not in heart failure.

    Gong, Yanjun; Feng, Yundi; Chen, Xudong; Tan, Wenchang; Huo, Yunlong; Kassab, Ghassan S


    It is scientifically and clinically important to understand the structure-function scaling of coronary arterial trees in compensatory (e.g., left and right ventricular hypertrophy, LVH and RVH) and decompensatory vascular remodeling (e.g., congestive heart failure, CHF). This study hypothesizes that intraspecific scaling power laws of vascular trees are preserved in hypertrophic hearts but not in CHF swine hearts. To test the hypothesis, we carried out the scaling analysis based on morphometry and hemodynamics of coronary arterial trees in moderate LVH, severe RVH, and CHF compared with age-matched respective control hearts. The scaling exponents of volume-diameter, length-volume, and flow-diameter power laws in control hearts were consistent with the theoretical predictions (i.e., 3, 7/9, and 7/3, respectively), which remained unchanged in LVH and RVH hearts. The scaling exponents were also preserved with an increase of body weight during normal growth of control animals. In contrast, CHF increased the exponents of volume-diameter and flow-diameter scaling laws to 4.25 ± 1.50 and 3.15 ± 1.49, respectively, in the epicardial arterial trees. This study validates the predictive utility of the scaling laws to diagnose vascular structure and function in CHF hearts to identify the borderline between compensatory and decompensatory remodeling.

  17. Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy.

    Hoh Boon-Peng

    Full Text Available Left ventricular hypertrophy (LVH is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

  18. Blood pressure circadian rhythm and heart rate turbulence in hypertensive patients: relationship with left ventricular hypertrophy

    Mei Zhu; Mohan Liu; Xinhong Guo; Shiwen Wang


    Objective To investigate the relationship of blood pressure circadian rhythm with myocardial hypertrophy and the changes of autonomic nerve function in patients with essential hypertension (EH). Methods Eighty-two female patients with essential hypertension (EH) underwent 24-hours ambulatory blood pressure monitorings (ABPM), dynamic electrocardiogram (Holter) and echocardiography examination. Patients were classified into non-dipping group (n=40) and dipping group (n=42) according to the result of ABPM. Left ventricular mass index (LVMI), heart rate variability (HRV) in time domain (including SDNN, SDANN, rMSSD, PNN50) and heart rate turbulence (HRT) parameters (including turbulence onset [TO] and turbulence slope [TS]) were measured. Results Compared with those in dipping group, patients in non-dipping group have higher incidence of LVH (19.0% vs 52.5%, P<0.01), greater mean LVMI (112.39±12.79 g/m2 vs 121.98±13.35 g/m2, P<0.01), decreased PNN50 and rMSSD. TS value was decreased while TO was increased in non-dipping group compared with those in dipping group (both P <0.01); patients with LVH showed decreased TS and increased TO, compared with those without LVH. Conclusion In female patients with EH, non-dipping blood pressure circadian is associated with higher incidence of LVH. The HRV and HRT were more remarkably blunted in non-dipping patients, as well as those with LVH.

  19. Dynamical mechanisms of phase-2 early afterdepolarizations in human ventricular myocytes: insights from bifurcation analyses of two mathematical models.

    Kurata, Yasutaka; Tsumoto, Kunichika; Hayashi, Kenshi; Hisatome, Ichiro; Tanida, Mamoru; Kuda, Yuhichi; Shibamoto, Toshishige


    Early afterdepolarization (EAD) is known as a cause of ventricular arrhythmias in long QT syndromes. We theoretically investigated how the rapid (IKr) and slow (IKs) components of delayed-rectifier K(+) channel currents, L-type Ca(2+) channel current (ICaL), Na(+)/Ca(2+) exchanger current (INCX), Na(+)-K(+) pump current (INaK), intracellular Ca(2+) (Cai) handling via sarcoplasmic reticulum (SR), and intracellular Na(+) concentration (Nai) contribute to initiation, termination, and modulation of phase-2 EADs, using two human ventricular myocyte models. Bifurcation structures of dynamical behaviors in model cells were explored by calculating equilibrium points, limit cycles (LCs), and bifurcation points as functions of parameters. EADs were reproduced by numerical simulations. The results are summarized as follows: 1) decreasing IKs and/or IKr or increasing ICaL led to EAD generation, to which mid-myocardial cell models were especially susceptible; the parameter regions of EADs overlapped the regions of stable LCs. 2) Two types of EADs (termination mechanisms), IKs activation-dependent and ICaL inactivation-dependent EADs, were detected; IKs was not necessarily required for EAD formation. 3) Inhibiting INCX suppressed EADs via facilitating Ca(2+)-dependent ICaL inactivation. 4) Cai dynamics (SR Ca(2+) handling) and Nai strongly affected bifurcations and EAD generation in model cells via modulating ICaL, INCX, and INaK Parameter regions of EADs, often overlapping those of stable LCs, shifted depending on Cai and Nai in stationary and dynamic states. 5) Bradycardia-related induction of EADs was mainly due to decreases in Nai at lower pacing rates. This study demonstrates that bifurcation analysis allows us to understand the dynamical mechanisms of EAD formation more profoundly.

  20. Differentially expressed phosphoproteins in diazoxide-pretreated ventricular myocytes by two-dimensional electrophoresis and mass spectrometry in vitro

    LI Hong; XIAO Ying-bin; GAO Yu-qi; YANG Tian-de


    Objective:To analyze and identify differentially expressed phosphoproteins associated with mitochondrial KATP channel opening. Methods: Adult rat ventricular myocytes were isolated, cultured,and identified, and pretreated without or with 100μmol/L diazoxide for 10 min. Phosphoproteins prepared and enriched from the control and diazoxide-pretreated cells were separated by two-dimensional gel electrophoresis (2-DE) followed by sliver staining. The obtained interesting phosphoproteins were further identified by mass spectrometry. Results: Associated with diazoxide preconditioning, the proteins of chaperonin containing TCP-1 and hypothetical protein XP_ 346548 were phosphorylated significantly (P<0. 01), while the 94-kDa glucose-regulated protein, calpactin I heavy chain and ferritin were dephosphorylated markedly (P<0. 01). Conclusion: These findings suggest that cardiomyocytes undergo significant posttranslational modification via phosphorylation in a multitude of proteins in order to respond diazoxide preconditioning, and these phosphorylated protein may mediate the downstream signaling of cardioprotection by mitochondrial KATP channel opening induced by ischemic preconditioning.

  1. Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

    Delin Wu


    Full Text Available Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA. However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (IK, the rapidly activating (IKr and slowly activating (IKs components of IK, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record IK (IKr, IKs and the HERG K+ current. Results. GA (1, 5, and 10 μM inhibited IK (IKr, IKs and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of IK (IKr, IKs and HERG K+ channel.

  2. Constitutive Intracellular Na+ Excess in Purkinje Cells Promotes Arrhythmogenesis at Lower Levels of Stress Than Ventricular Myocytes From Mice With Catecholaminergic Polymorphic Ventricular Tachycardia

    Willis, B. Cicero; Pandit, Sandeep V.; Ponce-Balbuena, Daniela; Zarzoso, Manuel; Guerrero-Serna, Guadalupe; Limbu, Bijay; Deo, Makarand; Camors, Emmanuel; Ramirez, Rafael J.; Mironov, Sergey; Herron, Todd J.; Valdivia, Héctor H.


    Background— In catecholaminergic polymorphic ventricular tachycardia (CPVT), cardiac Purkinje cells (PCs) appear more susceptible to Ca2+ dysfunction than ventricular myocytes (VMs). The underlying mechanisms remain unknown. Using a CPVT mouse (RyR2R4496C+/Cx40eGFP), we tested whether PC intracellular Ca2+ ([Ca2+]i) dysregulation results from a constitutive [Na+]i surplus relative to VMs. Methods and Results— Simultaneous optical mapping of voltage and [Ca2+]i in CPVT hearts showed that spontaneous Ca2+ release preceded pacing-induced triggered activity at subendocardial PCs. On simultaneous current-clamp and Ca2+ imaging, early and delayed afterdepolarizations trailed spontaneous Ca2+ release and were more frequent in CPVT PCs than CPVT VMs. As a result of increased activity of mutant ryanodine receptor type 2 channels, sarcoplasmic reticulum Ca2+ load, measured by caffeine-induced Ca2+ transients, was lower in CPVT VMs and PCs than respective controls, and sarcoplasmic reticulum fractional release was greater in both CPVT PCs and VMs than respective controls. [Na+]i was higher in both control and CPVT PCs than VMs, whereas the density of the Na+/Ca2+ exchanger current was not different between PCs and VMs. Computer simulations using a PC model predicted that the elevated [Na+]i of PCs promoted delayed afterdepolarizations, which were always preceded by spontaneous Ca2+ release events from hyperactive ryanodine receptor type 2 channels. Increasing [Na+]i monotonically increased delayed afterdepolarization frequency. Confocal imaging experiments showed that postpacing Ca2+ spark frequency was highest in intact CPVT PCs, but such differences were reversed on saponin-induced membrane permeabilization, indicating that differences in [Na+]i played a central role. Conclusions— In CPVT mice, the constitutive [Na+]i excess of PCs promotes triggered activity and arrhythmogenesis at lower levels of stress than VMs. PMID:27169737

  3. Effects and mechanism of different adrenergic receptor antagonists on left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats

    HU Qin; LI Long-gui; ZHANG Yun


    To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the ef-fects of three kinds of adrenergic receptor blockers: Carvedilol (CAR), Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypearophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA) was used in this study. Thirty two male istar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER.emodynamics, ventric-ular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ /Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ/Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ/Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was indepen-dent of beta-adrenergic receptor antagonist.


    Aleksandra Zebrowska


    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

  5. Physiological and pathological left ventricular hypertrophy of comparable degree is associated with characteristic differences of in vivo hemodynamics.

    Oláh, Attila; Németh, Balázs Tamás; Mátyás, Csaba; Hidi, László; Lux, Árpád; Ruppert, Mihály; Kellermayer, Dalma; Sayour, Alex Ali; Szabó, Lilla; Török, Marianna; Meltzer, Anna; Gellér, László; Merkely, Béla; Radovits, Tamás


    Left ventricular (LV) hypertrophy is a physiological or pathological response of LV myocardium to increased cardiac load. We aimed at investigating and comparing hemodynamic alterations in well-established rat models of physiological hypertrophy (PhyH) and pathological hypertrophy (PaH) by using LV pressure-volume (P-V) analysis. PhyH and PaH were induced in rats by swim training and by abdominal aortic banding, respectively. Morphology of the heart was investigated by echocardiography. Characterization of cardiac function was completed by LV P-V analysis. In addition, histological and molecular biological measurements were performed. Echocardiography revealed myocardial hypertrophy of similar degree in both models, which was confirmed by post-mortem heart weight data. In aortic-banded rats we detected subendocardial fibrosis. Reactivation of fetal gene program could be observed only in the PaH model. PhyH was associated with increased stroke volume, whereas unaltered stroke volume was detected in PaH along with markedly elevated end-systolic pressure values. Sensitive indexes of LV contractility were increased in both models, in parallel with the degree of hypertrophy. Active relaxation was ameliorated in athlete's heart, whereas it showed marked impairment in PaH. Mechanical efficiency and ventriculo-arterial coupling were improved in PhyH, whereas they remained unchanged in PaH. Myocardial gene expression of mitochondrial regulators showed marked differences between PaH and PhyH. We provided the first comparative hemodynamic characterization of PhyH and PaH in relevant rodent models. Increased LV contractility could be observed in both types of LV hypertrophy; characteristic distinction was detected in diastolic function (active relaxation) and mechanoenergetics (mechanical efficiency), which might be explained by mitochondrial differences.

  6. The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.

    Hui Pang

    Full Text Available 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 and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson's trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2 and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2 protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA content and increased superoxide dismutase (SOD activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM

  7. ECG is an inefficient screening-tool for left ventricular hypertrophy in normotensive African children population

    Giuseppe Di Gioia


    Full Text Available Background Left ventricular hypertrophy (LVH is a marker of pediatric hypertension and predicts development of cardiovascular events. Electrocardiography (ECG screening is used in pediatrics to detect LVH thanks to major accessibility, reproducibility and easy to use compared to transthoracic echocardiography (TTE, that remains the standard technique. Several diseases were previously investigated, but no data exists regarding our study population. The aim of our study was to evaluate the relationship between electrocardiographic and echocardiographic criteria of LVH in normotensive African children. Methods We studied 313 children (mean age 7,8 ± 3 yo, in north-Madagascar. They underwent ECG and TTE. Sokolow-Lyon index was calculated to identify ECG-LVH (>35 mm. Left ventricle mass (LVM with TTE was calculated and indexed by height2.7 (LVMI2.7 and weight (LVMIw. We report the prevalence of TTE-LVH using three methods: (1 calculating percentiles age- and sex- specific with values >95th percentile identifying LVH; (2 LVMI2.7 >51 g/m2.7; (3 LVMIw >3.4 g/weight. Results 40 (13% children showed LVMI values >95th percentile, 24 children (8% an LVMI2.7 >51 g/m2.7 while 19 children (6% an LVMIw >3.4 g/kg. LVH-ECG by Sokolow-Lyon index was present in five, three and three children respectively, with poor values of sensitivity (ranging from 13 to 16%, positive predictive value (from 11 to 18% and high values of specificity (up to 92%. The effects of anthropometrics parameters on Sokolow-Lyon were analyzed and showed poor correlation. Conclusion ECG is a poor screening test for detecting LVH in children. In clinical practice, TTE remains the only tool to be used to exclude LVH.

  8. The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.

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


    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 and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson's trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition

  9. Circulating level of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis.

    Zhongxiu Chen

    Full Text Available Excessively high left ventricle mass is an independent predictor of adverse prognosis. MicroRNAs (miRs play crucial roles in the regulation of left ventricle hypertrophy (LVH. However, few circulating miRs have been established as predictors of LVH in aortic stenosis (AS patients. In this study, we aimed to investigate whether circulating levels of miR-1, miR-133, and miR-378 predict LVH in patients with AS.One-hundred twelve patients with moderate to severe AS and 40 healthy controls were included in the study. Levels of miR-1, miR-133, and miR-378 in the plasma were measured by qPCR. Compared with healthy controls, AS patients had significantly lower circulating levels of miR-1, miR-133, and miR-378. AS patients with LVH had significantly lower miR-378 but not miR-1 and miR-133 compared with those without LVH. Linear regression analysis showed circulating miR-378 had strong correlation with left ventricular mass index (r = 0.283, p = 0.002 and logistic regression showed that lower miR-378 was an independent predictor for LVH in patients with AS (p = 0.037, OR 4.110, 95% CI 1.086 to 15.558.Circulating levels of miR-1, miR-133 and miR-378 were decreased in AS patients, and miR-378 predicts LVH independent of the pressure gradient. Further prospective investigations are needed to elucidate whether these circulating miRs affect clinical outcome.

  10. Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy.

    Caselli, Stefano; Maron, Martin S; Urbano-Moral, Josè A; Pandian, Natesa G; Maron, Barry J; Pelliccia, Antonio


    Identification of hypertrophic cardiomyopathy (HC) in young athletes is challenging when left ventricular (LV) wall thickness is between 13 and 15 mm. The aim of this study was to revise the ability of simple echocardiographic and clinical variables for the differential diagnosis of HC versus athlete's heart. Twenty-eight athletes free of cardiovascular disease were compared with 25 untrained patients with HC, matched for LV wall thickness (13 to 15 mm), age, and gender. Clinical, electrocardiographic, and echocardiographic variables were compared. Athletes had larger LV cavities (60 ± 3 vs 45 ± 5 mm, p 40 mm excluded HC with sensitivity of 92% and specificity of 71% (p <0.001). Athletes showed higher e' velocity by tissue Doppler imaging than patients with HC (12.5 ± 1.9 vs 9.3 ± 2.3 cm/second, p <0.001), with values <11.5 cm/second yielding sensitivity of 81% and specificity of 61% for the diagnosis of HC (p <0.001). Absence of diffuse T-wave inversion on electrocardiography (specificity 92%) and negative family history for HC (specificity 100%) also proved useful for excluding HC. In conclusion, in athletes with LV hypertrophy in the "gray zone" with HC, LV cavity size appears the most reliable criterion to help in diagnosis, with a cut-off value of <54 mm useful for differentiation from athlete's heart. Other criteria, including LV diastolic dysfunction, absence of T-wave inversion on electrocardiography, and negative family history, further aid in the differential diagnosis.

  11. Computational analysis of the regulation of Ca2+ dynamics in rat ventricular myocytes

    Bugenhagen, Scott M.; Beard, Daniel A.


    Force-frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca2+ signaling plays an important role in shaping the force-frequency relationship, and understanding the properties of the force-frequency relationship in vivo requires an understanding of Ca2+ dynamics under physiologically relevant conditions. Ca2+ signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca2+ dynamics via β-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca2+ signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca2+ dynamics are not currently well understood. In order to better understand Ca2+ dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include β-adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) β-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that

  12. Impact of 1, 25-(OH)2D3 on Left Ventricular Hypertrophy in Type 2 Diabetic Rats

    Ying Fan; Shan-xiao Zhang; Meng Ren; Li-feng Hong; Xiao-ni Yan


    Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups:untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.

  13. Loss of the eIF2α kinase GCN2 protects mice from pressure overload induced congestive heart failure without affecting ventricular hypertrophy

    Lu, Zhongbing; Xu, Xin; Fassett, John; Kwak, Dongmin; Liu, Xiaoyu; Hu, Xinli; Wang, Huan; Guo, Haipeng; Xu, Dachun; Yan, Shuo; McFalls, Edward O.; Lu, Fei; Bache, Robert J.; Chen, Yingjie


    In response to a number of stresses, including nutrient deprivation, General Control Nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2 alpha (eIF2αSer51). Energy starvation is known to exacerbate congestive heart failure (CHF) and eIF2αSer51 phosphorylation is increased in the failing heart. However, the impact of GCN2 during the evolution of CHF has not been tested. In this study we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with Transverse Aortic Constriction (TAC) in Wild Type (WT) and GCN2 knockout (GCN2−/−) mice. Under basal conditions, GCN2−/− had normal LV structure or function but following TAC, demonstrated less contractile dysfunction, less increase of lung weight, less increase of lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with WT mice, despite an equivalent degree of LV hypertrophy. As expected, GCN2−/− attenuated TAC induced cardiac eif2αSer51 phosphorylation and preserved Sarcoplasmic reticulum Ca2+ ATPase (Serca2a) expression compared with WT mice. Interestingly, expression of the anti-apoptotic protein Bcl-2 was significantly elevated in GCN2−/− hearts, while in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development. PMID:24166753

  14. Effect of cardiac glycosides on action potential characteristics and contractility in cat ventricular myocytes: role of calcium overload.

    Ruch, Stuart R; Nishio, Manabu; Wasserstrom, J Andrew


    There is increasing evidence that cardiac glycosides act through mechanisms distinct from inhibition of the sodium pump but which may contribute to their cardiac actions. To more fully define differences between agents indicative of multiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides (ouabain, ouabagenin, dihydroouabain, actodigin, digoxin, and resibufogenin). AP shortening was observed only with ouabain and actodigin. There was extensive inotropic variability between agents, with some giving full inotropic effects before automaticity occurred whereas others produced minimal inotropy before toxicity. AP shortening was not a result of alterations in calcium current or the inward rectifier potassium current, but correlated with an increase in steady-state outward current (Iss), which was sensitive to KB-R7943, a Na+-Ca2+ exchange (NCX) inhibitor. Interestingly, Iss was observed following exposure to ouabain and dihydroouabain, suggesting that an additional mechanism is operative with dihydroouabain that prevents AP shortening. Further investigation into differences in inotropy between ouabagenin, dihydroouabain and ouabain revealed almost identical responses under AP voltage clamp. Thus all agents appear to act on the sodium pump and thereby secondarily increase the outward reverse mode NCX current, but the extent of AP duration shortening and positive inotropy elicited by each agent is limited by development of their toxic actions. The quantitative differences between cardiac glycosides suggest that mechanisms independent of sodium pump inhibition may result from an altered threshold for calcium overload possibly involving direct or indirect effects on calcium release from the sarcoplasmic reticulum.

  15. Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI.

    Bastiaan J van Nierop

    Full Text Available BACKGROUND: Left ventricular (LV and right ventricular (RV function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure. METHODS: MRI was used to quantify RV and LV function and morphology in healthy (n = 4 and sham operated (n = 3 C57BL/6 mice, and animals with a mild (n = 5 and a severe aortic constriction (n = 10. RESULTS: Mice subjected to a mild constriction showed increased LV mass (P0.05. Animals with a severe constriction progressively developed LV hypertrophy (P<0.001, depressed LVEF (P<0.001, followed by a declining RVEF (P<0.001 and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05. CONCLUSIONS: Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.


    S. K. Kukushkin


    Full Text Available Moscow Aim – to study the prevalence of arterial hypertension (AH and left ventricular hypertrophy among male liquidators (ML of Chernobyl accident consequences and a group of unorganized males (UM from one of the Moscow regions. Materials and methods. The results of examining a random representative sample of three hundred and ninety-five 35–64-year-old Mos-cow Registry MLs of Chernobyl accident consequences (n = 395; 79 % response rate were analyzed. A random sample of males from one of the Moscow regions (n = 382; 70 % response rate was used to make up an age-matched comparison group.Results. The age-adjusted prevalence rate (AAPR of AH according to the expanded WHO criteria (> 140/90 Hg mm was substantially higher among MLs than among UMs (64.9 and 54.7 %, respectively; p < 0.01. The prevalence of AH was associated with the men’s age in both populations. Thus, this among MLs and UMs in the 35–44 year age group was 54.6 and 47.2 %, respectively and in the 55–64 year age group 80 and 62.2 % (i.e. the incidence of AH increased by 1.3 (р < 0.01 and 1.2 (р < 0.05 times, respectively. Conclusion. AAPR of AH among the liquidators was significantly higher than that in the control group (64.9 % versus 54.7 %, respectively. In the compared groups, that of left ventricular hypertrophy did not differ and was 25 and 25.6 %, respectively; significant differences were found in the degree of left ventricular hypertrophy: certain (concentric left ventricular hypertrophy was more common in the liquidators than in the comparison group (12.9 % versus 7.4 %, respectively. In the ML group compared to the control group, there was much higher awareness of having AH (59.1 % versus 46 %, respectively, drug treatment was performed in 38.7 % versus 7.9 %; effective BP control in the patients was 13.1 % versus 4.7 %, respectively.

  17. Physiological left ventricular hypertrophy or hypertrophic cardiomyopathy in an elite adolescent athlete: role of detraining in resolving the clinical dilemma

    Basavarajaiah, S; Wilson, M; Junagde, S; Jackson, G; Whyte, G; Sharma, S


    The differentiation of physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) can prove challenging for even the most experienced cardiologists. The case is presented of a 17 year old elite swimmer who had electrocardiographic and echocardiographic features that were highly suggestive of HCM. However, indices of diastolic function were normal and cardiopulmonary exercise testing revealed high peak oxygen consumption in keeping with physiological LVH. To resolve the diagnostic dilemma, the patient underwent detraining for eight weeks, after which, there was complete resolution of the changes seen on electrocardiogram and echocardiogram, indicating physiological LVH rather than HCM. PMID:16864569

  18. Negative inotropic effect of a CB2 agonist A-955840 in isolated rabbit ventricular myocytes is independent of CB1 and CB2 receptors.

    Su, Zhi; Preusser, Lee; Diaz, Gilbert; Green, Jonathon; Liu, Xiaoqin; Polakowski, James; Dart, Michael; Yao, Betty; Meyer, Michael; Limberis, James T; Martin, Ruth L; Cox, Bryan F; Gintant, Gary A


    A-955840, a selective CB2 agonist, has been shown to elicit concentration-dependent decreases in cardiac contractility in the anesthetized dog (decreased maximal velocity of left ventricular pressure development [LV dP/dt max]). However, it is unknown whether this represents a direct effect or a response dependent on other factors (such as autonomic tone and neurohumoral factors) present in vivo. This study examined if A-955840 had a direct effect on contractility of isolated cardiac myocytes, and if so to determine the potential mechanisms. Contractility was assessed in vitro using percent changes in maximal shortening velocity of sarcomeres (dL/dt max) and fractional shortening of sarcomere length (FS) in rabbit left ventricular myocytes. L-type calcium current in myocytes was recorded using wholecell voltage-clamp techniques. A-955840 reduced dL/dt max and FS in a reversible and concentration-dependent manner with an IC50 of 11.4 μg/mL (based on dL/dt max) which is similar to the estimated IC50 value of 9.8 μg/mL based on the effects of A-955840 on LV dP/dt max in anesthetized dogs. A-955840 (4.1 μg/mL) reduced myocyte contractility (%FS) to a similar extent in the absence and presence of a CB2 antagonist, SR-2 (24.0 ± 3.4 vs 23.1 ± 3.0 %, n=5) or a CB1 antagonist, Rimonabant (18.8 ± 2.3 vs 19.8 ± 2.7 %, n=5). A-955840 (4.1 μg/mL) also reduced L-type calcium current of rabbit ventricular myocytes (1.05 ± 0.11 vs 0.70 ± 0.12 nA, n=5, P CB2 nor CB1 receptors, and consistent with off-target negative inotropy mediated by inhibition of the cardiac L-type calcium current.

  19. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes

    FENG Li; GONG Jing; JIN Zhen-yi; LI Ning; SUN Li-ping; WU Yi-ling; PU Jie-lin


    Background Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n=8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). Results SSYX treatment accelerated the HR from (141.8±36.0) beats per minute to (163.0±38.0) beats per minute (P=0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD30, APD50 and APDgo were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD3o and APD9o did not significantly change.Conclusions The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

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

    Xiang, Yu-luan; He, Li [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiao, Jun [Department of Cardiology, Chongqing Emergency Medical Center, Chongqing (China); Xia, Shuang; Deng, Song-bai [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiu, Yun [Institute of Life Science, Chongqing Medical University, Chongqing (China); She, Qiang [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)


    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 (I{sub to}) 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{sup −1}·day{sup −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 I{sub to} 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 I{sub to} 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 I{sub to} of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

  1. Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies.

    Ng, Sze Ying; Wong, Chun Kit; Tsang, Suk Ying


    Myocardial infarction has been the leading cause of morbidity and mortality in developed countries over the past few decades. The transplantation of cardiomyocytes offers a potential method of treatment. However, cardiomyocytes are in high demand and their supply is extremely limited. Embryonic stem cells (ESCs), which have been isolated from the inner cell mass of blastocysts, can self-renew and are pluripotent, meaning they have the ability to develop into any type of cell, including cardiomyocytes. This suggests that ESCs could be a good source of genuine cardiomyocytes for future therapeutic purposes. However, problems with the yield and purity of ESC-derived cardiomyocytes, among other hurdles for the therapeutic application of ESC-derived cardiomyocytes (e.g., potential immunorejection and tumor formation problems), need to be overcome before these cells can be used effectively for cell replacement therapy. ESC-derived cardiomyocytes consist of nodal, atrial, and ventricular cardiomyocytes. Specifically, for treatment of myocardial infarction, transplantation of a sufficient quantity of ventricular cardiomyocytes, rather than nodal or atrial cardiomyocytes, is preferred. Hence, it is important to find ways of increasing the yield and purity of specific types of cardiomyocytes. Atrial and ventricular cardiomyocytes have differential expression of genes (transcription factors, structural proteins, ion channels, etc.) and are functionally distinct. This paper presents a thorough review of differential gene expression in atrial and ventricular myocytes, their expression throughout development, and their regulation. An understanding of the molecular and functional differences between atrial and ventricular myocytes allows discussion of potential strategies for preferentially directing ESCs to differentiate into chamber-specific cells, or for fine tuning the ESC-derived cardiomyocytes into specific electrical and contractile phenotypes resembling chamber

  2. Angiotensin II receptor blockers and cardiovascular protection: Focus on left ventricular hypertrophy regression and atrial fibrillation prevention

    Cesare Cuspidi


    Full Text Available Cesare Cuspidi1,2, Francesca Negri2, Alberto Zanchetti31Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; 2Policlinico di Monza; 3Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, and Istituto Auxologico Italiano, Milan, ItalyAbstract: Left ventricular hypertrophy (LVH and atrial fibrillation (AF are strong predictors of cardiovascular (CV morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or recurrent AF, it is reasonable to consider this class of drugs among first line therapies in patients with hypertension and LVH (a very high risk phenotype predisposing to AF and as adjunctive therapy to antiarrhythmic agents in patients undergoing pharmacological or electrical cardioversion of AF.Keywords: angiotensin II receptor blockers, left ventricular hypertrophy, atrial fibrillation

  3. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.


    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  4. Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats

    Xiong, Xingjiang; Yang, Xiaochen; Duan, Lian; Liu, Wei; Zhang, Yun; Liu, Yongmei; Wang, Pengqian; Li, Shengjie; Li, Xiaoke


    Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension. PMID:28225023

  5. Down-regulation of replication factor C-40 (RFC40 causes chromosomal missegregation in neonatal and hypertrophic adult rat cardiac myocytes.

    Hirotaka Ata

    Full Text Available BACKGROUND: Adult mammalian cardiac myocytes are generally assumed to be terminally differentiated; nonetheless, a small fraction of cardiac myocytes have been shown to replicate during ventricular remodeling. However, the expression of Replication Factor C (RFC; RFC140/40/38/37/36 and DNA polymerase δ (Pol δ proteins, which are required for DNA synthesis and cell proliferation, in the adult normal and hypertrophied hearts has been rarely studied. METHODS: We performed qRT-PCR and Western blot analysis to determine the levels of RFC and Pol δ message and proteins in the adult normal cardiac myocytes and cardiac fibroblasts, as well as in adult normal and pulmonary arterial hypertension induced right ventricular hypertrophied hearts. Immunohistochemical analyses were performed to determine the localization of the re-expressed DNA replication and cell cycle proteins in adult normal (control and hypertrophied right ventricle. We determined right ventricular cardiac myocyte polyploidy and chromosomal missegregation/aneuploidy using Fluorescent in situ hybridization (FISH for rat chromosome 12. RESULTS: RFC40-mRNA and protein was undetectable, whereas Pol δ message was detectable in the cardiac myocytes isolated from control adult hearts. Although RFC40 and Pol δ message and protein significantly increased in hypertrophied hearts as compared to the control hearts; however, this increase was marginal as compared to the fetal hearts. Immunohistochemical analyses revealed that in addition to RFC40, proliferative and mitotic markers such as cyclin A, phospho-Aurora A/B/C kinase and phospho-histone 3 were also re-expressed/up-regulated simultaneously in the cardiac myocytes. Interestingly, FISH analyses demonstrated cardiac myocytes polyploidy and chromosomal missegregation/aneuploidy in these hearts. Knock-down of endogenous RFC40 caused chromosomal missegregation/aneuploidy and decrease in the rat neonatal cardiac myocyte numbers. CONCLUSION: Our

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

    Wachtell, Kristian; Okin, Peter M; Olsen, Michael H;


    -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......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...

  7. Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes.

    Horváth, Balázs; Váczi, Krisztina; Hegyi, Bence; Gönczi, Mónika; Dienes, Beatrix; Kistamás, Kornél; Bányász, Tamás; Magyar, János; Baczkó, István; Varró, András; Seprényi, György; Csernoch, László; Nánási, Péter P; Szentandrássy, Norbert


    Ca(2+)-activated Cl(-) current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca(2+) cycling and AP voltage-clamp) as well as in conditions designed to change [Ca(2+)]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined. The possible spatial distribution of these proteins and their co-localization with Cav1.2 was also studied. The profile of ICl(Ca), identified as a 9-anthracene carboxylic acid-sensitive current under AP voltage-clamp conditions, contained an early fast outward and a late inward component, overlapping early and terminal repolarizations, respectively. Both components were moderately reduced by ryanodine, while fully abolished by BAPTA, but not EGTA. [Ca(2+)]i was monitored using Fura-2-AM. Setting [Ca(2+)]i to the systolic level measured in the bulk cytoplasm (1.1μM) decreased ICl(Ca), while application of Bay K8644, isoproterenol, and faster stimulation rates increased the amplitude of ICl(Ca). Ca(2+)-entry through L-type Ca(2+) channels was essential for activation of ICl(Ca). TMEM16A and Bestrophin-3 showed strong co-localization with one another and also with Cav1.2 channels, when assessed using immunolabeling and confocal microscopy in both canine myocytes and human ventricular myocardium. Activation of ICl(Ca) in canine ventricular cells requires Ca(2+)-entry through neighboring L-type Ca(2+) channels and is only augmented by SR Ca(2+)-release. Substantial activation of ICl(Ca) requires high Ca(2+) concentration in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA.

  8. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David


    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases.

  9. Resveratrol attenuates the Na(+-dependent intracellular Ca(2+ overload by inhibiting H(2O(2-induced increase in late sodium current in ventricular myocytes.

    Chunping Qian

    Full Text Available BACKGROUND/AIMS: Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2O(2-induced increase in late sodium current (I(Na.L which augmented the reverse Na(+-Ca(2+ exchanger current (I(NCX, and the diastolic intracellular Ca(2+ concentration in ventricular myocytes. METHODS: I(Na.L, I(NCX, L-type Ca(2+ current (I(Ca.L and intracellular Ca(2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix, respectively, in rabbit ventricular myocytes. RESULTS: Resveratrol (10, 20, 40 and 80 µM decreased I(Na.L in myocytes both in the absence and presence of H(2O(2 (300 µM in a concentration dependent manner. Ranolazine (3-9 µM and tetrodotoxin (TTX, 4 µM, I(Na.L inhibitors, decreased I(Na.L in cardiomyocytes in the presence of 300 µM H(2O(2. H(2O(2 (300 µM increased the reverse I(NCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2O(2 of the diastolic intracellular Ca(2+ fura-2 fluorescence intensity (FFI, fura-fluorescence intensity change (△FFI, maximal velocity of intracellular Ca(2+ transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L. CONCLUSION: Resveratrol protects the cardiomyocytes by inhibiting the H(2O(2-induced augmentation of I(Na.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias.

  10. Relationship of left ventricular systolic function to persistence or development of electrocardiographic left ventricular hypertrophy in hypertensive patients

    Okin, Peter M; Wachtell, Kristian; Gerdts, Eva;


    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...... 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...

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

    Sipola, Petri [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); University of Eastern Finland, Institute of Clinical Medicine, Faculty of Health Sciences, Kuopio (Finland); Magga, Jarkko; Peuhkurinen, Keijo [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Husso, Minna [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); Jaeaeskelaeinen, Pertti; Kuusisto, Johanna [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Kuopio University Hospital, Heart Center, P.O. Box 1777, Kuopio (Finland)


    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 {alpha}-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.)

  12. Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation

    Okin, Peter M; Gerdts, Eva; Wachtell, Kristian;


    Persistence and development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of atrial fibrillation compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via greater left atrial...

  13. High fat/low carbohydrate diet attenuates left ventricular hypertrophy and prevents myosin heavy chain isoform switching induced by chronic hypertenstion

    A switch in the expression of myosin heavy chain isoform (MHC) alpha to beta is observed with left ventricular hypertrophy (LVH) and heart failure. This switch is associated with a defect in myocardial energy production and contractile dysfunction. Similar MHC isoform profile is observed in the fe...

  14. Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation

    Okin, Peter M; Gerdts, Eva; Wachtell, Kristian


    Persistence and development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of atrial fibrillation compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via greater left atrial...... enlargement (LAE) in patients with new and persistent ECG LVH....

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

    Boersma Hester


    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

  16. A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation

    Sana, Maria Elena; Quilliam, Lawrence A.; Spitaleri, Andrea; Pezzoli, Laura; Marchetti, Daniela; Lodrini, Chiara; Candiago, Elisabetta; Lincesso, Anna Rita; Ferrazzi, Paolo; Iascone, Maria


    Several genetic conditions can lead to left ventricular hypertrophy (LVH). Among them, hypertrophic cardiomyopathy (HCM), caused by mutations in sarcomere genes, is the most common inherited cardiac disease. Instead, RASopathies, a rare class of disorders characterized by neuro-cardio-facial-cutaneous abnormalities and sometimes presenting with LVH, are caused by mutations in the RAS-MAPK pathway. We report on a 62-years-old male who presented isolated severe obstructive LVH but did not carry the sarcomere mutation previously identified in his affected relatives. By exome sequencing, we detected a novel mutation in HRAS gene (NM_005343.2:p.Arg68Trp), present also in the proband’s daughter, who showed mild LVH and severe intellectual disability. The cardiac phenotype was indistinguishable between family members carrying either mutation. In silico studies suggested that the mutated HRAS protein is constitutionally activated. Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Our study emphasizes the role of RAS signaling in cardiac hypertrophy and highlights the complexity in differential diagnosis of RASopathies. In fact, the mild features of RASopathy and the recurrence of sarcomeric HCM in this family delayed the correct diagnosis until comprehensive genetic testing was performed. PMID:28002430

  17. Enhancement of Ca2 + transients and contraction of single ventricular myocytes of rats by 5- ( N, N-dimethyl) amiloride%DMA增加正常大鼠心肌细胞钙瞬变和收缩

    崔香丽; 陈还珍; 武冬梅; 吴博威


    The effects of 5-( N, N-dimethyl) amiloride (DMA) ( a blocker of Na +/H + exchanger or Na +/Ca2 + exchanger) on calcium transient and cell contraction in isolated ventricular myocytes in normal rats and rats with myocardial hypertrophy were examined using ion imaging system with a charge coupled digital camera ( CCD camera). Loading myocytes with Fura-2, electrically triggered Ca2+ transients and cell shortening were measured simultaneously. The results showed that 10 μmol/L DMA increased Ca2+ transient and cell shortening from 209.60 +54.96 and 3.07 ±0.97 μm to 238.50 ±80.41 and 4.07 ± 1.02 μn, respectively ( P < 0.05 ) , which was completely abolished by application of KB-R7943, a specific reverse mode Na +/Ca2+ exchanger blocker. After blocking L-type Ca2+ channels by nicardipine, DMA also enhanced Ca2 + transient and cell shortening. In rats with myocardial hypertrophy, DMA showed the common pharmacologic profile as in normal rats but more intense stimulating effects on Ca2+ transient and eell contraction. The results suggest that DMA increase Ca2+ transient and cell contraction via stimulating reverse mode Na+/Ca2+ exchange, and the stimulating effect is more pronounced in rats with myocardial hypertrophy than in normal ones.%实验观察了钠氢交换或钠钙交换抑制剂5-(N,N-二甲基)氨氯吡咪(DMA)对正常和心肌肥厚大鼠分离心室肌细胞钙瞬变和细胞收缩的影响.通过负载荧光染料Fura-2/Am,应用离子影像分析系统(Ion Imaging System)同步测定离体大鼠心肌细胞钙瞬变和细胞长度.结果表明:DMA 10 μ,mol/L分别使钙瞬变和细胞缩短从对照组的209.60±54.96和3.07±0.971μm增加到238.50±80.41和4.07±1.02μmn(P<0.05,n=7).应用特异性反向钠钙交换阻断剂KB-R7943可完全阻断DMA的激动作用.DMA还可使尼卡地平抑制L-型钙通道后的钙瞬变和细胞收缩增加.在肥厚心肌细胞,DMA表现出相同的药理作用,但对钙瞬变和细胞缩短的刺激作

  18. Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

    Salem, K A; Adrian, T E; Qureshi, M A; Parekh, K; Oz, M; Howarth, F C


    There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0

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

    Cabral A.M.


    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

  20. Electrocardiogram and echocardiographic study of left ventricular hypertrophy in patients with essential hypertension in a teaching medical college

    K Venugopal


    Full Text Available Background: Left ventricular hypertrophy (LVH is the adaptive mechanism for increased left ventricular (LV stress and is associated with many adverse events. This study was undertaken to study LVH in patients of essential hypertension and to correlate between clinical, electrocardiogram (ECG, and echocardiography (ECHO in the identification of LVH. Materials and Methods: One hundred patients attending the outpatient department and those who were admitted in our teaching institute from January 2013 to June 2014 were the study subjects. All cases of essential hypertension, irrespective of the duration of hypertension and type of treatment received were included in the study. Patients with secondary hypertension, ischemic heart disease/myocardial infarction, ischemic cardiomyopathy, congenital heart disease, and valvular heart disease were excluded. Conclusion: Out of the different ECG criteria, total QRS criteria showed a high sensitivity of 60%. ECG criteria have a high specificity but low sensitivity and hence, have limited use as a screening method. However, in a resource-poor country such as India where ECHO facilities are not available in all rural regions, improved ECG criteria such as total QRS voltage can be recommended as a routine investigation for LVH because of its cost-effectiveness and easy availability despite certain limitations.

  1. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy; By sup 201 Tl myocardial SPECT

    Yamazaki, Junichi; Ohsawa, Hidefumi; Uchi, Takashi (Toho Univ., Tokyo (Japan). School of Medicine) (and others)


    {sup 201}Tl 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).

  2. Barnidipine or Lercanidipine on Echocardiographic Parameters in Hypertensive, Type 2 Diabetics with Left Ventricular Hypertrophy: A Randomized Clinical Trial.

    Derosa, Giuseppe; Mugellini, Amedeo; Querci, Fabrizio; Franzetti, Ivano; Pesce, Rosa Maria; D'Angelo, Angela; Maffioli, Pamela


    The aim of this study was to evaluate the effects of lercanidipine or barnidipine on echocardiographic parameters, in hypertensive, type 2 diabetics with left ventricular hypertrophy. One hundred and forty-four patients were randomized to lercanidipine, 20 mg/day, or barnidipine, 20 mg/day, in addition to losartan, 100 mg/day, for 6 months. We evaluated: blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA(1c)), lipid profile, creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, and acid uric. Echocardiography was performed at baseline and after 6 months. Both lercanidipine and barnidipine decreased blood pressure. Left ventricular mass index was reduced to a greater extent with barnidipine + losartan. Interventricular septal thickness in diastole was reduced by barnidipine + losartan. Posterior wall thickness in diastole was decreased by both treatments, even if barnidipine + losartan were more effective. Ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction was increased by barnidipine + losartan, but not by lercanidipine + losartan. Finally, isovolumetric relaxation and time and left atrial volume index were reduced by barnidipine + losartan, while lercanidipine + losartan did not affect them. In conclusion, barnidipine + losartan provided a greater improvement of echocardiographic parameters compared to lercanidipine + losartan.

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

    T.A. Uggere


    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

  4. AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress.

    Ma, Yuedong; Huang, Huiling; Jiang, Jingzhou; Wu, Lingling; Lin, Chunxi; Tang, Anli; Dai, Gang; He, Jiangui; Chen, Yili


    AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.

  5. Changes in Myocardial Mass Associated with Age and Stress: Reexamination of Ventricular Hypertrophy.

    George, Colleen; And Others


    One hundred twenty-six rats were studied to determine the effects of exercise, high altitude, and age upon right and left ventricular mass. Chronically hypoxic rats had significantly larger right ventricles but significantly smaller left ventricles than exercised or control rats. (Author/MT)

  6. Development of cellular hypertrophy by 8-hydroxyeicosatetraenoic acid in the human ventricular cardiomyocyte, RL-14 cell line, is implicated by MAPK and NF-κB.

    Maayah, Zaid H; Abdelhamid, Ghada; El-Kadi, Ayman O S


    Recent studies have established the role of mid-chain hydroxyeicosatetraenoic acids (mid-chain HETEs) in the development of cardiovascular disease. Among these mid-chains, 8-HETE has been reported to have a proliferator and proinflammatory action. However, whether 8-HETE can induce cardiac hypertrophy has never been investigated before. Therefore, the overall objectives of the present study are to elucidate the potential hypertrophic effect of 8-HETE in the human ventricular cardiomyocytes, RL-14 cells, and to explore the mechanism(s) involved. Our results showed that 8-HETE induced cellular hypertrophy in RL-14 cells as evidenced by the induction of cardiac hypertrophy markers ANP, BNP, α-MHC, and β-MHC in a concentration- and time-dependent manner as well as the increase in cell surface area. Mechanistically, 8-HETE was able to induce the NF-κB activity as well as it significantly induced the phosphorylation of ERK1/2. The induction of cellular hypertrophy was associated with a proportional increase in the formation of dihydroxyeicosatrienoic acids (DHETs) parallel to the increase of soluble epoxide hydrolase (sEH) enzyme activity. Blocking the induction of NF-κB, ERK1/2, and sEH signaling pathways significantly inhibited 8-HETE-induced cellular hypertrophy. Our study provides the first evidence that 8-HETE induces cellular hypertrophy in RL-14 cells through MAPK- and NF-κB-dependent mechanism

  7. Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study.

    Lombardi, G; Colao, A; Marzullo, P; Biondi, B; Palmieri, E; Fazio, S


    We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8+/-6.9 vs 140.7+/-7.1 g/m2, paffect systolic function, whereas it increased the Doppler-derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34+/-0.1 vs 1.09+/-0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134+/-14 vs 129+/-13 mmHg, p50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (>50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile.

  8. Myocyte repolarization modulates myocardial function in aging dogs.

    Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A; Wunimenghe, Oriyanhan; Michler, Robert E; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G; Anversa, Piero; Hintze, Thomas H; Rota, Marcello


    Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

  9. Association of Late Gadolinium Enhancement and Degree of Left Ventricular Hypertrophy Assessed on Cardiac Magnetic Resonance Imaging With Ventricular Tachycardia in Children With Hypertrophic Cardiomyopathy.

    Spinner, Joseph A; Noel, Cory V; Denfield, Susan W; Krishnamurthy, Rajesh; Jeewa, Aamir; Dreyer, William J; Maskatia, Shiraz A


    There are limited data on the clinical significance of left ventricular (LV) mass and late gadolinium enhancement (LGE) in pediatric hypertrophic cardiomyopathy (HC). We reviewed cardiovascular magnetic resonance (CMR) studies of children with HC to investigate the associations between the extent and distribution of LGE and LV mass with ventricular tachycardia (VT) in children with HC. A blinded observer reviewed CMR studies for the presence and distribution of LV hypertrophy and LGE using a 17-segment model. The primary outcome was VT. LGE was present 17 of 33 subjects (52%). VT was present on outpatient Holter monitor or exercise stress test in 7 patients, of which 5 patients (71%) had LGE. Each additional segment of LGE was associated with an increase in the odds of VT (odds ratio [OR] 1.4, 95% CI 1.1 to 1.9) and fewer than 5 segments with LGE had 93% specificity for the presence or absence of VT (OR 0.06, 95% CI 0.01 to 0.5). VT was more common in patients with LGE in the apical septal (p = 0.03), basal inferoseptal (p <0.01), and basal inferior (p = 0.04) segments, whereas LGE in more commonly involved segments (midanteroseptal and midinferoseptal) was not associated with VT (p = 0.13, 0.26). Patients with VT had greater LV mass index (76.4 ± 40.4 g/m(2.7) vs 50.9 ± 24.3 g/m(2.7); p = 0.03). Each centimeter of increased maximum LV thickness was associated with increased likelihood of VT (OR 2.9, 95% CI 1.2 to 6.8). In conclusion, in pediatric HC, CMR to evaluate the extent and pattern of LGE, LV mass index, and maximum LV thickness may help to identify children with HC at risk of VT.

  10. Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

    Ulerich, J.; Göktepe, S.; Kuhl, E.

    This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

  11. Anemia treatment and left ventricular hypertrophy in non-dialysis chronic kidney disease

    Robert N. Foley; Peter A. McCullough


    @@ To this day, the target hemoglobin level that minimizes cardiovascular risk in chronic kidney disease (CKD) patients remains unclear. When one examines the many randomized trials of epoetin therapy in aggregate, enhanced quality of life provides the most cogent argument for hemoglobin levels above 110 g/L. It remains unclear whether treatment of anemia improves longevity, or even a surrogate marker (such as left ventricular [LV] mass index), especially when applied at earlier phases of CKD.

  12. Decreased KCNE2 expression participates in the development of cardiac hypertrophy

    DENG Jian-xin; LIU Wen-juan; DING Wen-wen; WANG Gang; LIU Jie


    AIM:To investigate whether KCNE 2 participates in the development of pathological hypertrophy .METHODS:Bidirectional ma-nipulations of KCNE2 expression were performed by adenoviral overexpression of KCNE 2 or knockdown of KCNE2 with RNA interfer-ence in PE-induced neonatal rat ventricular myocytes .Then overexpression of KCNE 2 in mouse model of left ventricular hypertrophy in-duced by transverse aortic constriction (TAC) by ultrasound microbubble-mediated gene transfer were used to detect the therapeutic function of KCNE2 in the development of hypertrophy .RESULTS:KCNE2 expression was significantly decreased in PE-induced hy-pertrophic cardiomyocytes and in hypertrophic hearts produced by TAC .Knockdown of KCNE2 in cardiomyocytes reproduced hypertro-phy, whereas overexpression of KCNE2 attenuated PE-induced cardiomyocyte hypertrophy .Knockdown of KCNE2 increased calcineurin activity and nuclear NFAT protein level , and pretreatment with nifedipine or FK 506 attenuated decreased KCNE 2-induced cardiomyo-cyte hypertrophy .Overexpression of KCNE 2 in heart by ultrasound microbubble-mediated gene transfer suppressed the development of hypertrophy and activation of calcineurin-NFAT and MAPK pathways in TAC mice .CONCLUSION:These findings demonstrate that cardiac KCNE2 expression is decreased and contributes to the development of hypertrophy via activation of calcineurin -NFAT and MAPK pathways .

  13. Effect of irbesartan combined with Xinkeshu capsule on blood pressure and left cardiac function in patients with hypertension merged with left ventricular hypertrophy

    Shen-Qing Cui; Li-Cha Kong; Xin Ling; Min Huang


    Objective:To observe the effect of irbesartan combined with Xinkeshu capsule on the blood pressure, and left cardiac structure and function in patients with hypertension merged with left ventricular hypertrophy.Methods:A total of 100 patients with hypertension merged with left ventricular hypertrophy who were admitted in our hospital from January, 2015 to December, 2015 were included in the study and randomized into the experiment group and the control group with 50 cases in each group. The patients in the experiment group were given irbesartan combined with Xinkeshu capsule, while the patients in the control group were only given irbesartan. A continuous 6-month treatment was regarded as one course. The blood pressure before and after treatment in the two groups was compared. The color Doppler ultrasound cardiograph was used to detect LVSD, LVDPWT, LVDD, LVMI, LVEF, SV, and CO.Results:The difference of SBP and DBP before operation between the two groups was not statistically significant (P>0.05). SBP and DBP after treatment were significantly reduced (P<0.05). SBP and DBP after treatment in the experiment group were significantly lower than those in the control group (P<0.05). LVDPWT, LVDD, LVM, and LVSD after treatment in the experiment group were significantly lower than those in the control group at the same stage (P<0.05). LVEF, SV, and CO after treatment in the experiment group were significantly higher than those in the control group at the same stage (P<0.05).Conclusions:Irbesartan combined with Xinkeshu capsule can effectively control the blood pressure in patients with hypertension merged with left ventricular hypertrophy, improve the myocardial remodeling, and reverse the left ventricular hypertrophy, with a significant effect.

  14. Effect of microalbuminuria-lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension

    Assadi F ; Translated by: Akbari Asbagh P


    Full Text Available Background: Microalbuminuria (MA is associated with increased cardiovascular risk in hypertensive patients, but not many studies have specifically examined the effects of MA-lowering on regression of left ventricular hypertrophy (LVH among pediatric patients with hypertension. Methods: Fifty-five patients with essential hypertension, 11 to 19 years old were prospectively studied. All patients received concomitant therapy of hydrochlorothiazide and angiotensin-converting-enzyme inhibitor. Five patients also required angiotensin-receptor blocker to achieve the blood pressure goal. Baseline and 12-month follow-up measures of left ventricular mass index (LVMI determined by echocardiography and urine microalbumin/creatinine ratio (MA/Cr were collected. MA was defined as MA/Cr>30. LVH was defined as LVMI>38.6 g/m2. The primary end points were 25% or more reductions in MA and the LVMI. Results: Weight (r=0.83, body surface area (r=0.85, body mass index (BMI (r=0.86, systolic blood pressure (SBP (r=0.57, diastolic blood pressure (DBP (r=0.49, mean arterial pressure (r=0.53 and MA (r=0.87 were all univariate correlates of LVMI. In a multiple regression analysis, MA, BMI and SBP were significant correlates of LVMI. MA alone explained 76% of the variance of LVMI, whereas BMI and SBP explained only 1.6% and 0.4% of the variance, respectively. MA was the most significant correlate of follow-up LVMI after BMI and SBP were included in the overall multiple regression models. Conclusion: MA is a strong predictor of LVH in hypertensive children and adolescents. MA-lowering halts the progression of LVH or induces its regression.

  15. Impact of dry weight determined by calf bioimpedance ratio on carotid stiffness and left ventricular hypertrophy in hemodialysis patients.

    Zhou, Yi-Lun; Liu, Jing; Ma, LiJie; Sun, Fang; Shen, Yang; Huang, Jing; Cui, TaiGen


    Our previous study has shown that modification of bioimpedance technique by the measurement of bioimpedance ratio in the calf (calf-BR) was a simple and practical method in assessing fluid status in hemodialysis patients. However, the consequences of periodical dry weight (DW) adjustment under the guidance of calf-BR on target organ damage have not been investigated. One hundred fifteen hemodialysis patients were enrolled in this pilot trial. Patients were divided into bioimpedance group and control group according to their dialysis schedule. In the bioimpedance group, DW was routinely adjusted under the guidance of calf-BR every 3 months. In the control group, the assessment of DW remained a clinical judgment. Carotid stiffness, left ventricular mass index (LVMI), and calf-BR were measured at baseline and at the 12th month in both groups. Home blood pressure (BP) was monitored monthly. Episodes of dialysis-related adverse events were recorded. No significant differences were observed in parameters between the two groups at baseline. Compared with the control group, the bioimpedance group had significantly lower values in terms of the annual averages of systolic home BP (147.4 ± 15.3 mm Hg vs. 152.6 ± 16.9 mm Hg, P = 0.019), carotid stiffness index β (10.7 ± 3.3 vs. 12.2 ± 3.1, P = 0.003), LVMI (155.21 ± 15.64 g/m(2) vs. 165.17 ± 16.76 g/m(2) , P measurement improved arterial stiffness and left ventricular hypertrophy with good tolerability in hemodialysis patients.

  16. Electrocardiogram Performance in the Diagnosis of Left Ventricular Hypertrophy in Hypertensive Patients With Left Bundle Branch Block

    Burgos, Paula Freitas Martins; Luna Filho, Bráulio; Costa, Francisco de Assis; Bombig, Maria Teresa Nogueira; de Souza, Dilma; Bianco, Henrique Tria; Oliveira Filho, Japy Angelini; Izar, Maria Cristina de Oliveira; Fonseca, Francisco Antonio Helfenstein; Póvoa, Rui


    Background Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular events, and its detection usually begins with an electrocardiogram (ECG). Objective To evaluate the impact of complete left bundle branch block (CLBBB) in hypertensive patients in the diagnostic performance of LVH by ECG. Methods A total of 2,240 hypertensive patients were studied. All of them were submitted to an ECG and an echocardiogram (ECHO). We evaluated the most frequently used electrocardiographic criteria for LVH diagnosis: Cornell voltage, Cornell voltage product, Sokolow-Lyon voltage, Sokolow-Lyon product, RaVL, RaVL+SV3, RV6/RV5 ratio, strain pattern, left atrial enlargement, and QT interval. LVH identification pattern was the left ventricular mass index (LVMI) obtained by ECHO in all participants. Results Mean age was 11.3 years ± 58.7 years, 684 (30.5%) were male and 1,556 (69.5%) were female. In patients without CLBBB, ECG sensitivity to the presence of LVH varied between 7.6 and 40.9%, and specificity varied between 70.2% and 99.2%. In participants with CLBBB, sensitivity to LVH varied between 11.9 and 95.2%, and specificity between 6.6 and 96.6%. Among the criteria with the best performance for LVH with CLBBB, Sokolow-Lyon, for a voltage of ≥ 3,0mV, stood out with a sensitivity of 22.2% (CI 95% 15.8 - 30.8) and specificity of 88.3% (CI 95% 77.8 - 94.2). Conclusion In hypertensive patients with CLBBB, the most often used criteria for the detection of LVH with ECG showed significant decrease in performance with regards to sensitivity and specificity. In this scenario, Sokolow-Lyon criteria with voltage ≥3,0mV presented the best performance. PMID:27992034

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

    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


    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.)

  18. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats.

    Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

    Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.


    K. I. Pshenichkin


    Full Text Available Aim. To study the effects of antihypertensive therapy based on consideration of individual heart rhythm variability (HRV on left ventricular hypertrophy (LVH in hypertensive elderly patients.Material and methods. 60 hypertensive elderly patients with LVH were included in the study. They were split in two groups (30 people in each one. Patients of the group-I had common antihypertensive therapy. Patients of group-II received medications prescribed with consideration of individual heart rate variability. Holter monitoring with analysis of HRV, 24-hour blood pressure monitoring and ultrasonography were conducted initially and 18 months after treatment beginning.Results. BP control was reached in the majority of patients of both groups. The patients of group-II in comparison with patients of group-I had reduction of low- high frequency power ratio (LF/HF and higher rate of LVH reduction. Relationship between LVH dynamics and ratio LF/HF was found.Conclusion. Arterial hypertension therapy considering individual HRV contributes in LVH reduction in elderly patients.


    B. Amarjagal


    Full Text Available Aim. To study change of rate and duration indicators of longitudinal movement of a fibrous ring of mitral valve (MFR during isovolumic contraction (IVC and relaxation (IVR in hypertensive patients with various degree of a left ventricular hypertrophy (LVH.Material and methods. 80 hypertensive patients with moderate LVH (n=40 and severe LVH (n=40 are examined. The control group was presented by 30 healthy volunteers. Transthoracic echocardiography and Tissue Doppler imaging has been performed with ultrasonic tomograph “HDI 5000” (Philips.Results. Increase in LVH (Smm and Е/Еmm associates with reduction in systolic velocity of movement of medial MFR (Smm. There is direct relation with duration of IVC-negative and IVR-positive components and myocardium mass index. Maximal velocity of IVC-positive component increases and maximal velocity of IVR-negative component decreases when LVH is growing.Conclusion. Velocities curves of IVC and IVR were bi-phase both in healthy persons and in hypertensive patients with LVH. Velocity and duration of positive and negative components of IVC and IVR depended on LVH degree.


    B. Amarjagal


    Full Text Available Aim. To study change of rate and duration indicators of longitudinal movement of a fibrous ring of mitral valve (MFR during isovolumic contraction (IVC and relaxation (IVR in hypertensive patients with various degree of a left ventricular hypertrophy (LVH.Material and methods. 80 hypertensive patients with moderate LVH (n=40 and severe LVH (n=40 are examined. The control group was presented by 30 healthy volunteers. Transthoracic echocardiography and Tissue Doppler imaging has been performed with ultrasonic tomograph “HDI 5000” (Philips.Results. Increase in LVH (Smm and Е/Еmm associates with reduction in systolic velocity of movement of medial MFR (Smm. There is direct relation with duration of IVC-negative and IVR-positive components and myocardium mass index. Maximal velocity of IVC-positive component increases and maximal velocity of IVR-negative component decreases when LVH is growing.Conclusion. Velocities curves of IVC and IVR were bi-phase both in healthy persons and in hypertensive patients with LVH. Velocity and duration of positive and negative components of IVC and IVR depended on LVH degree.

  2. Mid-septal hypertrophy and apical ballooning; potential mechanism of ventricular tachycardia storm in patients with hypertrophic cardiomyopathy.

    Hwang, Eui-Seock; Pak, Hui-Nam


    Medically refractory ventricular tachycardia (VT) storm can be controlled with radiofrequency catheter ablation (RFCA), however, it may be difficult to control in some patients with hemodynamic overload. We experienced a patient with intractable VT storm controlled by hemodynamic unloading. The patient had mid-septal hypertrophic cardiomyopathy with an implantable cardioverter defibrillator (ICD) back-up. Because of the severe mid-septal hypertrophy, his left ventricle (LV) had an hourglass-like morphology and showed apical ballooning; the focus of VT was at the border of apical ballooning. Although we performed VT ablation because of electrical storm with multiple ICD shocks, VT recurred 1 hour after procedure. As the post-RFCA monomorphic VT was refractory to anti-tachycardia pacing or ICD shock, we reduced the hemodynamic overload of LV with β-blockade, hydration, and sedation. VT spontaneously stopped 1.5 hours later and the patient has remained free of VT for 24 months with β-blockade alone. In patients with VT storm refractory to antiarrhythmic drugs or RFCA, the mechanism of mechano-electrical feedback should be considered and hemodynamic unloading may be an essential component of treatment.

  3. Independent influence of overweight and obesity on the regression of left ventricular hypertrophy in hypertensive patients: a meta-analysis.

    Zhang, Kun; Huang, Feifei; Chen, Jie; Cai, Qingqing; Wang, Tong; Zou, Rong; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui


    Overweight and obesity are associated with adverse cardiovascular outcomes. However, the role of overweight and obesity in left ventricular hypertrophy (LVH) of hypertensive patients is controversial. The aim of the current meta-analysis was to evaluate the influence of overweight and obesity on LVH regression in the hypertensive population.Twenty-eight randomized controlled trials comprising 2403 hypertensive patients (mean age range: 43.8-66.7 years) were identified. Three groups were divided according to body mass index: normal weight, overweight, and obesity groups.Compared with the normal-weight group, LVH regression in the overweight and obesity groups was more obvious with less reduction of systolic blood pressure after antihypertensive therapies (P regressing LVH in overweight and obese hypertensive patients (19.27 g/m, 95% confidence interval [15.25, 23.29], P regression was found in 24-h ambulatory blood pressure monitoring (ABPM) group and in relatively young patients (40-60 years' old) group (P Overweight and obesity are independent risk factors for LVH in hypertensive patients. Intervention at an early age and monitoring by ABPM may facilitate therapy-induced LVH regression in overweight and obese hypertensive patients.

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

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


    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-β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from MβCD-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 MβCD treatment. Selective activation of α-, β1-, and β2-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

  5. Follistatin like 1 Regulates Hypertrophy in Heart Failure with Preserved Ejection Fraction

    Wilson, Richard M.; Essick, Eric E.; Fowler, Conor T.; Nakamura, Kazuto; van den Hoff, Maurice; Ouchi, Noriyuki; Sam, Flora


    Objective We sought to determine whether Fstl1 plays a role in the regulation of cardiac hypertrophy in HFpEF. Background Heart failure (HF) with preserved ejection fraction (HFpEF), accounts for ~50% of all clinical presentations of HF and its prevalence is expected to increase. However, there are no evidence-based therapies for HFpEF; thus, HFpEF represents a major unmet need. Although hypertension is the single most important risk factor for HFpEF, with a prevalence of 60-89% from clinical trials and human HF registries, blood pressure therapy alone is insufficient to prevent and treat HFpEF. Follistatin like 1 (Fstl1), a divergent member of the follistatin family of extracellular glycoproteins, has previously been shown to be elevated in HF with reduced ejection fraction (HFrEF) and associated with increased left ventricular mass. Methods and Results In this study, blood levels of Fstl1 were increased in humans with HFpEF. This increase was also evident in mice with hypertension-induced HFpEF and adult rat ventricular myocytes stimulated with aldosterone. Treatment with recombinant Fstl1 abrogated aldosterone-induced cardiac myocyte hypertrophy, suggesting a role for Fstl1 in the regulation of hypertrophy in HFpEF. There was also a reduction in the E/A ratio, a measure of diastolic dysfunction. Furthermore, HFpEF induced in a mouse model that specifically ablates Fstl1 in cardiac myocytes (cFstl1-KO), showed exacerbation of HFpEF with worsened diastolic dysfunction. In addition, cFstl1-KO-HFpEF mice demonstrated more marked cardiac myocyte hypertrophy with increased molecular markers of anp and bnp expression. Conclusions These findings indicate that Fstl1exerts therapeutic effects by modulating cardiac hypertrophy in HFpEF. PMID:27430031

  6. Calpain Inhibition Reduces Amplitude and Accelerates Decay of the Late Sodium Current in Ventricular Myocytes from Dogs with Chronic Heart Failure

    Undrovinas, Albertas; Maltsev, Victor A.; Sabbah, Hani N.


    Calpain is an intracellular Ca2+ -activated protease that is involved in numerous Ca2+ dependent regulation of protein function in many cell types. This paper tests a hypothesis that calpains are involved in Ca2+ -dependent increase of the late sodium current (INaL) in failing heart. Chronic heart failure (HF) was induced in 2 dogs by multiple coronary artery embolization. Using a conventional patch-clamp technique, the whole-cell INaL was recorded in enzymatically isolated ventricular cardiomyocytes (VCMs) in which INaL was activated by the presence of a higher (1μM) intracellular [Ca2+] in the patch pipette. Cell suspensions were exposed to a cell- permeant calpain inhibitor MDL-28170 for 1–2 h before INaL recordings. The numerical excitation-contraction coupling (ECC) model was used to evaluate electrophysiological effects of calpain inhibition in silico. MDL caused acceleration of INaL decay evaluated by the two-exponential fit (τ1 = 42±3.0 ms τ2 = 435±27 ms, n = 6, in MDL vs. τ1 = 52±2.1 ms τ2 = 605±26 control no vehicle, n = 11, and vs. τ1 = 52±2.8 ms τ2 = 583±37 ms n = 7, control with vehicle, P<0.05 ANOVA). MDL significantly reduced INaL density recorded at –30 mV (0.488±0.03, n = 12, in control no vehicle, 0.4502±0.0210, n = 9 in vehicle vs. 0.166±0.05pA/pF, n = 5, in MDL). Our measurements of current-voltage relationships demonstrated that the INaL density was decreased by MDL in a wide range of potentials, including that for the action potential plateau. At the same time the membrane potential dependency of the steady-state activation and inactivation remained unchanged in the MDL-treated VCMs. Our ECC model predicted that calpain inhibition greatly improves myocyte function by reducing the action potential duration and intracellular diastolic Ca2+ accumulation in the pulse train. Conclusions Calpain inhibition reverses INaL changes in failing dog ventricular cardiomyocytes in the

  7. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    Zhang X


    Full Text Available Xinlu Zhang,1,* Xu Wang,2,* Feng Hu,1 Boda Zhou,3 Hai-Bin Chen,1 Daogang Zha,1 Yili Liu,1 Yansong Guo,4 Lemin Zheng,2 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 2The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, 3Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, Beijing, 4Department of Cardiovascular Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Drag-reducing polymers (DRPs, when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR. Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS or DRPs. Body weight (BW, heart rate (HR and systolic blood pressure (SBP were measured. Echocardiography was used to evaluate the changes in left ventricle (LV function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1 of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end

  8. Enalaprilato na prevenção da hipertrofia ventricular esquerda induzida pelo isoproterenol Enalaprilat prevents the left ventricular hypertrophy induced by isoproterenol

    Eduardo A. S. Costa


    Full Text Available OBJETIVO: Avaliar se o enalaprilato, droga inibidora da enzima de conversão da angiotensina I, previne a hipertrofia ventricular esquerda (HVE induzida pelo isoproterenol. MÉTODOS: Foram divididos em 4 grupos, 72 ratos Wistar-EPM: CON controle; ENA, tratados com enalaprilato (1mg/kg via subcutânea (sc por 8 dias; ISO, tratados com isoproterenol (0,3mg/kg via sc/8 dias e ENA+ISO, tratados simultaneamente com ambas as drogas. Em 10 animais de cada grupo foram determinadas a freqüência cardíaca (FC e a pressão arterial (PA e verificado o peso de ventrículo esquerdo (VE. Em 8 animais de cada grupo, fragmento do VE foi corado com hematoxilina-eosina e picro-sírius e preparado para estudo morfométrico e ultra-estrutural, respectivamente, com microscópio de luz e eletrônico. RESULTADOS: Nos grupos estudados (CON, ENA, ISO e ISO+ENA não ocorreram variações na PA. Os grupos ISO e ISO+ENA exibiram aumentos significantes na FC. O grupo ISO apresentou aumento significativo do peso do VE (PU= 0,821g e PS= 0,204g, quando comparado ao grupo CON. O grupo ENA não exibiu modificação de peso do VE quando comparado ao grupo CON (PU= 0,590g e PS= 0,139g. No grupo ENA+ISO (PU= 0,737g e PS= 0,177g constatou-se diferença de peso ao ser comparado aos grupos ISO e CON. A análise morfométrica e ultra-estrutural mostraram que o ISO induziu hipertrofia dos cardiomiócitos e aumento do tecido conjuntivo com depósito de fibras colágenas do tipo I. O enalaprilato associado com isoproterenol atenuou importantemente aquela manifestação. CONCLUSÃO: O enalaprilato inibiu a ação do isoproterenol sobre os cardiomiócitos, evitando parcialmente, na dose utilizada, a HVE e diminuindo também a quantidade de fibras colágenas.PURPOSE: To evaluate whether the enalaprilat, angiotensin I enzyme conversion inhibitor, could prevent the left ventricular hypertrophy (LVH induced by isoproterenol. METHODS: Seventy two adult Wistar-EPM rats were divided into four

  9. Association of systolic dysfunction with left ventricular hypertrophy and diastolic dysfunction in hypertensive patients.

    Piskorz, Daniel; Bongarzoni, Laureano; Citta, Luciano; Citta, Norberto; Citta, Paula; Keller, Luis; Tommasi, Alicia


    ntroducción: La presencia de disfunción sistólica no ha sido reconocida en pacientes (p) hipertensos. Objetivos: El objetivo del presente estudio es demostrar que los p hipertensos con hipertrofia ventricular izquierda (HVI) presentan disfunción sistólica, y que ella se incrementa cuando se asocia a disfunción diastólica (DD). Material y métodos: estudio observacional de corte transversal con la muestra recolectada en forma prospectiva de acuerdo a criterios de inclusión y exclusión preestablecidos. La función ventricular izquierda fue evaluada por ecocardiografía convencional, Doppler del orificio valvular mitral y Doppler tisular siguiendo las normativas internacionales. Los p fueron divididos en cuatro grupos de acuerdo a la presencia o ausencia de HVI y DD. Análisis estadístico: test t de students y test de ANOVA, significación estadística <0,05. Resultados: se incluyeron 292 p, 130 p (51 %) HVI- DD-; 36 p (5,9 %) HVI- DD+; 87 p (37,6 %) HVI+ DD-; y 39 p (5,5 %) HVI+ DD+. Los p con DD fueron de mayor edad, más frecuentemente mujeres, y su PA sistólica y presión aórtica central estaban más elevados. La velocidad de acortamiento longitudinal de las fibras miocárdicas, medida como onda s con Doppler tisular fue 6,3 +1,1 cm/seg en p HVI+ DD+, 7,2+1,3 cm/seg en p HVI+ DD-, 6,8+1,2 cm/seg en p HVI- DD+, y 7,8+0,6 cm/seg en p HVI- DD- (<0,005). Conclusiones: los p hipertensos presentan disfunción sistólica cuando la HVI está presente y es mayor cuando se asocia a DD.

  10. Thallium myocardial perfusion scans for the assessment of right ventricular hypertrophy in patients with cystic fibrosis. A comparison with other noninvasive techniques

    Newth, C.J.; Corey, M.L.; Fowler, R.S.; Gilday, D.L.; Gross, D.; Mitchell, I.


    The incidence of right ventricular hypertrophy in 32 patients with cystic fibrosis was studied using thallium 201 (TI-201) myocardial perfusion scans, and compared with other noninvasive techniques including electrocardiography, vectorcardiography, and M-mode echocardiography. The patients (mean age, 17.3 yr; range, 7 to 33) had a wide range of clinical and pulmonary abnormalities (mean Shwachman-Kulczycki score, 66.6). In the total study group, TI-201 scans, like the vectorcardiograms and the M-mode echocardiograms, gave a surprisingly high proportion of positive predictions for right ventricular hypertrophy (RVH) (44%). The correlations with all other noninvasive methods were uniformly poor, so caution must be exercised in using this technique to predict early RVH in order to follow the natural history of cor pulmonale in cystic fibrosis. At the time of the study, 6 patients had clinical evidence of right ventricular failure, and in this disease setting must have had RVH. In 3 patients, RVH was confirmed at autopsy, and it was successfully predicted by TI-201 scans in 5 of the 6 patients. The false negative scan may have been due to regional myocardial ischemia secondary to severe right ventricular failure. In contrast, the vectorcardiogram, using Fowler's new criteria, made a successful prediction of RVH in all 6 patients, and the electro cardiogram in only 3. Although the M-mode echocardiogram was abnormal in all patients, it would have predicted RVH (with increased right ventricular anterior wall thickness) in only 1 patient. We concluded that TI-201 myocardial perfusion cans are good at confirming RVH in cases with established right ventricular failure, but have no advantage over vectorcardiographic assessments, which are logistically easier to perform and carry no radiation risks.

  11. The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

    van de Veerdonk, Mariëlle C; Dusoswa, Sophie A; Marcus, J Tim; Bogaard, Harm-Jan; Spruijt, Onno; Kind, Taco; Westerhof, Nico; Vonk-Noordegraaf, Anton


    To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p TPM mass (β = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

  12. Abnormal Wave Reflections and Left Ventricular Hypertrophy Late After Coarctation of the Aorta Repair

    Quail, Michael A.; Short, Rebekah; Pandya, Bejal; Steeden, Jennifer A.; Khushnood, Abbas; Taylor, Andrew M.; Segers, Patrick


    Patients with repaired coarctation of the aorta are thought to have increased afterload due to abnormalities in vessel structure and function. We have developed a novel cardiovascular magnetic resonance protocol that allows assessment of central hemodynamics, including central aortic systolic blood pressure, resistance, total arterial compliance, pulse wave velocity, and wave reflections. The main study aims were to (1) characterize group differences in central aortic systolic blood pressure and peripheral systolic blood pressure, (2) comprehensively evaluate afterload (including wave reflections) in the 2 groups, and (3) identify possible biomarkers among covariates associated with elevated left ventricular mass (LVM). Fifty adult patients with repaired coarctation and 25 age- and sex-matched controls were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal-resolution spiral phase-contrast cardiovascular magnetic resonance flow sequence. These data were used to derive central hemodynamics and to perform wave intensity analysis noninvasively. Covariates associated with LVM were assessed using multivariable linear regression analysis. There were no significant group differences (P≥0.1) in brachial systolic, mean, or diastolic BP. However central aortic systolic blood pressure was significantly higher in patients compared with controls (113 versus 107 mm Hg, P=0.002). Patients had reduced total arterial compliance, increased pulse wave velocity, and larger backward compression waves compared with controls. LVM index was significantly higher in patients than controls (72 versus 59 g/m2, Pcoarctation of the aorta repair, including abnormal wave reflections that are associated with elevated LVM. PMID:28115510

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

    Sun, Yi-hua [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Yong-quan [Harbin Medical University, Harbin 150086 (China); Feng, Shan-li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Bao-xin; Pan, Zhen-wei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Xu, Chang-qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Li, Ting-ting [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Yang, Bao-feng, E-mail: [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)


    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca{sup 2+} 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 Ca{sup 2+} imaging, we found that the depletion of ER/SR Ca{sup 2+} stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca{sup 2+} ([Ca{sup 2+}]{sub i}), followed by sustained increase depending on extracellular Ca{sup 2+}. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na{sup +}/Ca{sup 2+} exchanger inhibitors, inhibited [Ca{sup 2+}]{sub i} relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl{sub 3}) or by an increased extracellular Ca{sup 2+}([Ca{sup 2+}]{sub o}) increased the concentration of intracelluar Ca{sup 2+}, whereas, the sustained elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of SKF96365. Similarly, the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of extracellular Ca{sup 2+}. Western blot analysis showed that GdCl{sub 3} increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl{sub 3}. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca{sup 2+}-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.

  14. 5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-κB-dependent mechanism.

    Maayah, Zaid H; El-Kadi, Ayman O S


    Recent studies have established the role of mid-chain hydroxyeicosatetraenoic acids (HETEs) in the development of cardiovascular disease. Mid-chain HETEs have been reported to have vasoconstrictive and pro-inflammatory effects. However, whether mid-chain HETEs can induce cardiac hypertrophy remains unclear. Therefore, the overall objective of the present study was to elucidate the potential hypertrophic effect of mid-chain HETEs in the human ventricular cardiomyocytes, RL-14 cells, and to explore the mechanisms involved. For this purpose, RL-14 cells were treated with increasing concentrations of mid-chain HETEs (2.5, 5, 10 and 20 µM). Thereafter, the cardiac hypertrophy markers and cell size were determined using real-time polymerase chain reaction and phase contrast imaging, respectively. Phosphorylated mitogen-activated protein kinase (MAPK) level and nuclear factor kappa B (NF-κB) binding activity were determined. Our results showed that mid-chain HETEs induced cellular hypertrophy in RL-14 cells as evidenced by the induction of cardiac hypertrophy markers, α- and β-myocin heavy chain and atrial and brain natriuretic peptide as well as the increase in cell size. Mechanistically, all mid-chain HETEs were able to induce the binding activity of NF-κB to its responsive element in a HETE-dependent manner, and they significantly induced the phosphorylation of ERK 1/2. The induction of cellular hypertrophy was associated with proportional increase in the formation of dihydroxyeicosatrienoic acids parallel to the increase of soluble epoxide hydrolase enzyme activity. In conclusion, our study provides the first evidence that mid-chain HETEs induce cellular hypertrophy in RL-14 cells through MAPK- and NF-κB-dependent mechanism.

  15. Ranolazine attenuates the enhanced reverse Na⁺-Ca²⁺ exchange current via inhibiting hypoxia-increased late sodium current in ventricular myocytes.

    Wang, Xiao-Jing; Wang, Lei-Lei; Fu, Chen; Zhang, Pei-Hua; Wu, Ying; Ma, Ji-Hua


    Ranolazine (RAN), a novel antianginal agent, inhibits the increased late sodium current (INa.L) under many pathological conditions. In this study, the whole-cell patch-clamp technique was used to explore the effects of RAN on INa.L and reverse Na(+)/Ca(2+) exchange current (INCX) in rabbit ventricular myocytes during hypoxia.Tetrodotoxin (TTX) at 2 μM or RAN at 9 μM decreased significantly INa.L and reverse INCX under normoxia and RAN had no further effects on both currents in the presence of TTX. RAN (3, 6, and 9 μM) attenuated hypoxia-increased INa.L and reverse INCX in a concentration-dependent manner. Hypoxia-increased INa.L and reverse INCX were inhibited by 2 μM TTX, whereas 9 μM RAN applied sequentially did not further decrease both currents. In another group, after both currents were decreased by 9 μM RAN, 2 μM TTX had no further effects in the presence of Ran. In monophasic action potential (MAP) recording, early after-depolarizations (EADs) were suppressed by RAN (9 μM) during hypoxia. In conclusion, RAN decreased reverse INCX by inhibiting INa.L in normoxia, concentration-dependently attenuated the increase of INa.L, which thereby decreased the reverse INCX, and obviously relieved EADs during hypoxia.

  16. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun


    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.

  17. Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular Myocyte of Guinea Pig

    林先明; 李真; 胡本容; 夏国瑾; 姚伟星; 向继洲


    Summary: The effects of Arecoline (Are) on calcium mobilization were investigated. In isolatedsingle ventricular myocyte of guinea pig, patch clamp whole cell recording techniques were used torecord the current of L-type calcium channel and cytosolic Ca2+ level ([Ca2+]i) labeled with fluo-rescence probe Fluo-3/AM was measured under a laser scanning confocal microscope. Results re-vealed that Are (3-100 μmol/L) could inhibit L-type calcium current in a concentration-depen-dent manner and the value of IC50 was 33. 73μmol/L (n= 5). In the absence of extracellular calci-um, the resting levels of [Ca2+]i was not affected by Are (n=6, P>0. 05), but pretreatmentwith Are (30 μmol/L) could significantly inhibit the [Ca2+]i elevation induced by caffeine (10mmol/L, n = 6, P < 0. 01). It was concluded that Are could inhibit not only calcium influxthrough L-type calcium channel but also calcium release from sarcoplasmic reticulum.

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

    Nabil Ghorayeb


    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

  19. Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

    Alexander P. Headley; Yan Li; Yi Zhang; Ji-Yong Ge; Qi-Fang Huang; Ji-Guang Wang


    Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy (LVH) in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism in Chinese. Methods We recorded 12-lead ECG (CardioSoft, v4.2) in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Comell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Comell product ECG criteria was used, the prevalence of LVH (20.7% and 4.8%, respectively) significantly (P<0.0001) increased with male gender (odds ratio [OR] 2.33 and 7.15) and systolic blood pressure (per 10 mm Hg increase, OR 1.46 and 1.33). If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake (OR 1.44, P=0.03) and body mass index (OR 0.83, P=0.0005). The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy (P=0.01). In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with Ⅱ subjects had significantly higher Sokolow-Lyon voltage amplitudes (29.8±0.6 vs. 28.0±20.5 mV, P=0.02) and higher risk of LVH (OR 1.74, 95% CI: 1. 12-2.69, P=0.01). Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy.

  20. Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

    Ernst, Michael E; Davis, Barry R; Soliman, Elsayed Z; Prineas, Ronald J; Okin, Peter M; Ghosh, Alokananda; Cushman, William C; Einhorn, Paula T; Oparil, Suzanne; Grimm, Richard H


    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.

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

    Mungrue K


    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

  2. Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

    Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi


    We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population.

  3. Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a powerful platform for gene discovery in left ventricular hypertrophy

    Degui eZhi


    Full Text Available Rationale: Left ventricular hypertrophy (LVH is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complimentary experimental approaches to identify novel genetic predictors of increased LV mass . Methods: Whole exome sequencing (WES was conducted in 7 African American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT. WES identified 31,426 missense or nonsense mutations (MS/NS which were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and family relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM were stimulated to induce hypertrophy; mRNA sequencing was used to determine expression differences associated with hypertrophy onset. Results: After correction for multiple testing, 295 MS/NS variants in 265 genes were associated with LVMHT. We identified 44 of 265 WES genes differentially expressed (P<0.05 in hypertrophied cells. To further prioritize these 44 candidates, 7 supportive statistical and annotation-based criteria were used to evaluate the relevance of these genes. Five genes, HLA-B, HTT, MTSS1, SLC5A12, THBS1, were each supported by 3 criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH and harbors conserved and predicted damaging variants. Conclusions: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci.

  4. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    Nina P. Hofmann


    Full Text Available Left ventricular (LV hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM, cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG, echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2, severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%, accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE by cardiac magnetic resonance (CMR. Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease.

  5. Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium.

    Friehs, Ingeborg; Cowan, Douglas B; Choi, Yeong-Hoon; Black, Kendra M; Barnett, Reanne; Bhasin, Manoj K; Daly, Christian; Dillon, Simon J; Libermann, Towia A; McGowan, Francis X; del Nido, Pedro J; Levitsky, Sidney; McCully, James D


    Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n = 6]. RV-PAB was achieved by banding the pulmonary artery (n = 6). Controls (n = 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.

  6. The relation between left ventricular hypertrophy and QT dispersion in patients with primary hypertension%原发性高血压患者左心室肥厚与QT离散度的关系



    目的:探讨原发性高血压患者左心室肥厚与QT离散度(QTd)的关系,阐明在高血压治疗中逆转心肌肥厚的意义。方法:选取原发性高血压患者160例,根据有无左心室肥厚分为两组,其中左心室肥厚者78例为LVH组;无左心室肥厚者82例为对照组。比较两组之间左心室改变及QTd差异。结果:LVH组与观察组QTd比较差异有统计学意义(P<0.01)。结论:高血压伴有左室肥厚者的复极离散度明显大于无左室肥厚者。%Objective:To explore the relation between left ventricular hypertrophy and QT dispersion in patients with primary hypertension,and clarify the significance of reversing myocardial hypertrophy in the treatment of hypertension.Methods:160 cases with primary hypertension were selected.They were divided into two groups according to the presence of left ventricular hypertrophy.78 cases had left ventricular hypertrophy as the LVH group.82 cases had non left ventricular hypertrophy as the observation group.The left ventricle changes and QTd differences of two groups were compared.Results:The QTd of the LVH group and the observation group were compared,and the difference was statistically significant(P<0.05).Conclusion:The dispersion of repolarization in hypertension patients with left ventricular hypertrophy is significantly higher than that of non left ventricular hypertrophy.


    谢协驹; 吉丽敏; 符史干


    objective:The present study was to investigate the role of alphal-adrenergic receptor blocking agent(phentolamine) in the hypertrophy of cardiaomyocyte induced by adrenaline.Methods:The measurement of cell surface area and[3H]-Leucine incorporation judged the hypertrophy of cardiaomyocyte in cultured neonatal rat myocardal cells,Results:The results showed that adrenaline could significantly increase cell.surface area promote[3H]-Leucine incorporation.Alphal-adrenergic blocking agent could markedly block effects of adrenaline increasing cell surface area and promoting [3H]-Leucine incorporation, Conclusions:These results suggest that alpha-adrenergic blocking agent can prevent the hypertrophy of cardiomyocytes induced by adrenaline in cultured neontal rat myocardal cells.%目的:观察α受体阻滞剂酚妥拉明对肾上腺素诱导的心肌细胞肥大的作用。方法:在培养新生大鼠心肌细胞上。通过测量心肌细胞表面积和[3H]-Leu的掺入量来判断心肌细胞肥大。结果:肾上腺素要明显增加心肌细胞表面和[3H]-亮氨酸([3H-Leu]的掺入量,α受体阻滞剂酚妥拉明能阻断肾上腺素增加心肌细胞表面积和[3H]-Leu掺入量的作用。结论:α受体阻滞有减轻肾上腺素诱导心肌细胞肥大的作用。

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

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


    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 Ca(2+) 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.

  9. Remodeling of the sarcomeric cytoskeleton in cardiac ventricular myocytes during heart failure and after cardiac resynchronization therapy.

    Lichter, Justin G; Carruth, Eric; Mitchell, Chelsea; Barth, Andreas S; Aiba, Takeshi; Kass, David A; Tomaselli, Gordon F; Bridge, John H; Sachse, Frank B


    Sarcomeres are the basic contractile units of cardiac myocytes. Recent studies demonstrated remodeling of sarcomeric proteins in several diseases, including genetic defects and heart failure. Here we investigated remodeling of sarcomeric α-actinin in two models of heart failure, synchronous (SHF) and dyssynchronous heart failure (DHF), as well as a model of cardiac resynchronization therapy (CRT). We applied three-dimensional confocal microscopy and quantitative methods of image analysis to study isolated cells from our animal models. 3D Fourier analysis revealed a decrease of the spatial regularity of the α-actinin distribution in both SHF and DHF versus control cells. The spatial regularity of α-actinin in DHF cells was reduced when compared with SHF cells. The spatial regularity of α-actinin was partially restored after CRT. We found longitudinal depositions of α-actinin in SHF, DHF and CRT cells. These depositions spanned adjacent Z-disks and exhibited a lower density of α-actinin than in the Z-disk. Differences in the occurrence of depositions between the SHF, CRT and DHF models versus control were significant. Also, CRT cells exhibited a higher occurrence of depositions versus SHF, but not DHF cells. Other sarcomeric proteins did not accumulate in the depositions to the same extent as α-actinin. We did not find differences in the expression of α-actinin protein and its encoding gene in our animal models. In summary, our studies indicate that HF is associated with two different types of remodeling of α-actinin and only one of those was reversed after CRT. We suggest that these results can guide us to an understanding of remodeling of structures and function associated with sarcomeres.

  10. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Ji, Yanyan Claire; Gray, Richard A; Fenton, Flavio H


    Heart failure (HF) affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement) as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF.

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

    Greve, Anders M; Boman, Kurt; Gohlke-Baerwolf, Christa


    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...

  12. 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

    Ariansen, Inger; Reims, Henrik M; Gjesdal, Knut


    . 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...

  13. Effect of temperature on the activation of myocardial KATP channel in guinea pig ventricular myocytes: a pilot study by whole cell patch clamp recording

    JIN San-qing; NIU Li-jun; DENG Chun-yu; YAO Zhi-bin; ZHOU Ying-jie


    Background The myocardial ATP sensitive potassium channel (KATP channel) has been known for more than two decades, the properties of this channel have been intensively investigated, especially the myocardial protection effect by opening this channel. Numerous studies, including hypothermic, using KATP agonists to achieve a hyperpolarizing cardioplegic arrest, have shown a better myocardial protection than potassium arrest.However, there is no evidence showing that KATP channel could be opened by its agonists under profound hypothermia. We investigated the effect of temperature on activation of myocardial KATP channel by nicorandil.Methods Isolated ventricular myocytes were obtained by collagenase digestion of the hearts of guinea pigs and stored in KB solution at 4℃. With a steady ground current, the myocytes were perfused with 1 mmol/L nicorandil until a steady IKATP occurred. Then the cells were perfused with 1 mmol/L nicorandil plus 1 μmol/L glybenclamide. Currents signals were recorded on whole cells using patch clamp technique at several temperatures. The temperature of the bath solution around myocytes was monitored and was controlled at 4℃,10℃, 20℃, 25℃ and 35℃ respectively. About 10 cells were tested at each temperature, the cells were considered useful only when the outward current could be induced by nicorandil and blocked by glybenclamide.All data were analyzed using Graphpad PRISM 3.0 (Graphpad, San Diego, CA, USA). Nonlinear curve fitting was done in Clampfit (Axon) or Sigmaplot (SPSS).Results At 4℃, 10℃, 20℃, 25℃ and 35℃, the time needed to open the myocardial KATP channel was (81.0±0)minutes, (50.5±11.7) minutes, (28.8±2.3) minutes, (9.4±10.2) minutes and (2.3± 1.0) minutes respectively (P=0.003). The linear relationship between temperature and time needed to open the channel was y (min) =(4348.790-124.277x)/60, where y (min) is time needed to open KATP channel, x is temperature, correlation coefficient r =-0.942 (P=0

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

    Mirella Pessoa Sant'Anna


    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, com 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.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 of 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

  15. Effect of naloxone on L-type calcium current in isolated rat ventricular myocytes%纳洛酮对大鼠心室肌细胞L型钙电流的影响

    王群超; 闻庆平


    Objective To evaluate the effect of naloxone on L-type calcium current (ICa-L) in isolated rat ventricular myocytes.Methods Adult SD rats of both sexes aged 8 weeks weighing 200-250 g were used in this study.Single cardiac ventricular myocytes were enzymatically isolated from SD rats.ICa-L was measured in ventricular myocytes and recorded using whole cell patch-clamp technique.Different concentrations (20 and 100 μg/ml) of naloxone were added to the cardiomyocytes.The effect of naloxone on ICa-L was evaluated.Results The peak current of ICa-L Was inhibited by naloxone in a concentration-dependent manner.Naloxone had no significant effect on steady-state activation curve.Conclusion Naloxone inhibits the L-type calcium channel of ventricular myocytes and exerts negative effect on ventricular muscle function.%目的 评价纳洛酮对大鼠心室肌细胞L型钙电流(ICa-L)的影响.方法 采用急性酶解法分离SD大鼠单个心室肌细胞,以全细胞膜片钳技术测定ICa-L.纳洛酮采用累积给药法,记录不同浓度(20和100μg/ml)纳洛酮作用下心室肌细胞ICa-L和给药前、后半激活电压.结果 20和100 μg/ml的纳洛酮分别使L型钙通道峰电流强度从给药前(341±30) pA降至(270±23) pA和(173±21) pA,与20μg/ml纳洛酮相比,100μg/ml纳洛酮给药后L型钙通道峰电流强度降低(P<0.05).20和100μg/ml纳洛酮给药前、后半激活电压比较差异无统计学意义(P>0.05).结论 纳洛酮可抑制大鼠心室肌细胞L型钙通道,具有心室肌负性肌力作用.

  16. Calpain inhibition reduces amplitude and accelerates decay of the late sodium current in ventricular myocytes from dogs with chronic heart failure.

    Albertas Undrovinas

    Full Text Available Calpain is an intracellular Ca²⁺-activated protease that is involved in numerous Ca²⁺ dependent regulation of protein function in many cell types. This paper tests a hypothesis that calpains are involved in Ca²⁺-dependent increase of the late sodium current (INaL in failing heart. Chronic heart failure (HF was induced in 2 dogs by multiple coronary artery embolization. Using a conventional patch-clamp technique, the whole-cell INaL was recorded in enzymatically isolated ventricular cardiomyocytes (VCMs in which INaL was activated by the presence of a higher (1 μM intracellular [Ca²⁺] in the patch pipette. Cell suspensions were exposed to a cell- permeant calpain inhibitor MDL-28170 for 1-2 h before INaL recordings. The numerical excitation-contraction coupling (ECC model was used to evaluate electrophysiological effects of calpain inhibition in silico. MDL caused acceleration of INaL decay evaluated by the two-exponential fit (τ₁ = 42±3.0 ms τ₂ = 435±27 ms, n = 6, in MDL vs. τ₁ = 52±2.1 ms τ₂ = 605±26 control no vehicle, n = 11, and vs. τ₁ = 52±2.8 ms τ₂ = 583±37 ms n = 7, control with vehicle, P<0.05 ANOVA. MDL significantly reduced INaL density recorded at -30 mV (0.488±0.03, n = 12, in control no vehicle, 0.4502±0.0210, n = 9 in vehicle vs. 0.166±0.05pA/pF, n = 5, in MDL. Our measurements of current-voltage relationships demonstrated that the INaL density was decreased by MDL in a wide range of potentials, including that for the action potential plateau. At the same time the membrane potential dependency of the steady-state activation and inactivation remained unchanged in the MDL-treated VCMs. Our ECC model predicted that calpain inhibition greatly improves myocyte function by reducing the action potential duration and intracellular diastolic Ca²⁺ accumulation in the pulse train.Calpain inhibition reverses INaL changes in failing dog ventricular

  17. Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study

    Fernández‐Jiménez, Rodrigo; Silva, Jacobo; Martínez‐Martínez, Sara; López‐Maderuelo, Mª Dolores; Nuno‐Ayala, Mario; García‐Ruiz, José Manuel; García‐Álvarez, Ana; Fernández‐Friera, Leticia; Pizarro, Tech Gonzalo; García‐Prieto, Jaime; Sanz‐Rosa, David; López‐Martin, Gonzalo; Fernández‐Ortiz, Antonio; Macaya, Carlos; Fuster, Valentin; Redondo, Juan Miguel; Ibanez, Borja


    Background Biomarkers are frequently used to estimate infarct size (IS) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy (LVH) on biomarker release in clinical and experimental myocardial infarction (MI). Methods and Results ST‐segment elevation myocardial infarction (STEMI) patients (n=140) were monitored for total creatine kinase (CK) and cardiac troponin I (cTnI) over 72 hours postinfarction and were examined by cardiac magnetic resonance (CMR) at 1 week and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and in sham‐operated pigs (n=8), and serial total CK and cTnI measurements were performed and CMR scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of LVH on total CK and cTnI release and IS estimated by CMR (gold standard). Receiver operating characteristic (ROC) curve analysis was performed to study the discriminatory capacity of the area under the curve (AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI expression was quantified in myocardial sections from LVH and sham‐operated pigs. In both the clinical and experimental studies, LVH was associated with significantly higher peak and AUC of cTnI, but not with differences in total CK. ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV dysfunction was significantly worse for patients with LVH. LVH did not affect the capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence analysis revealed significantly higher cTnI content in hypertrophic cardiomyocytes. Conclusions Peak and AUC of cTnI both significantly overestimate IS in the presence of LVH, owing to the higher troponin content per cardiomyocyte. In the setting of LVH, cTnI release during STEMI poorly predicts postinfarction LV dysfunction. LV mass should be taken into consideration when IS or LV function are estimated by troponin

  18. Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline.

    Kumar, Sandeep; Wei, Chuanyu; Thomas, Candice M; Kim, Il-Kwon; Seqqat, Rachid; Kumar, Rajesh; Baker, Kenneth M; Jones, W Keith; Gupta, Sudhiranjan


    Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been

  19. Bepridil differentially inhibits two delayed rectifier K(+) currents, I(Kr) and I(Ks), in guinea-pig ventricular myocytes.

    Wang, J C; Kiyosue, T; Kiriyama, K; Arita, M


    1. We investigated the effects of bepridil on the two components of the delayed rectifier K(+) current, i.e., the rapidly activating (I(Kr)) and the slowly activating (I(Ks)) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca(2+) current with nitrendipine (5 microM) or D600 (1 microM). 2. Bepridil decreased I(Ks) under blockade of I(Kr) with E4031 (5 microM), in a concentration-dependent manner. The concentration-dependent inhibition of I(Ks) by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC(50)) was found to be 6.2 microM. 3. The effect of bepridil on I(Kr) was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (coefficient=3.03) and the IC(50) was 13.2 microM. 5. These results suggest that bepridil at a clinical therapeutic concentration ( approximately 2 microM) selectively blocks I(Ks) but does not inhibit I(Kr). This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD.

  20. Contractility of isolated bovine ventricular myocytes is enhanced by intracellular injection of cardioactive glycosides. Evidence for an intracellular mode of action.

    Isenberg, G


    The contractions of isolated bovine left ventricular myocytes were evaluated by optically measuring the extent of unloaded shortening (ES), the maximal rate of shortening (MRS) and the maximal rate of re-lengthening (MRL). Ouabain, digoxin or digitoxin were intracellularly injected by 2 sec long pressure pulses via the microelectrodes. Their i.c. concentration was estimated to be 2-5 nM. Within 1-4 min after the injection, ES, MRS and MRL increased by more than 2-fold. The contractility renormalized within the following 20 min. Injection of solutions without glycosides did not increase the contractility. An interaction of the injected glycoside with the e.c. ouabain receptor could be largely excluded because a) the amount of the released glycoside was too small for e.c. effects, b) 500 nM e.c. antidigoxin, c) 20 mM [K]o or d) covalent binding of digoxin to HSA did not prevent the increase in contractility due to the i.c. injections. Since contractility also increased when the injections were performed at Na-free conditions, [Na]i-load is not necessary for the effect of i.e. glycosides. The increased contractility due to the injected glycosides was not observed when the contractility prior to the injection was already potentiated, e.g. by greater than 3.6 mM [Ca]o or by stimulation at frequencies greater than 1.25 Hz. The results are interpreted by the hypothesis that the i.c. glycosides facilitate the release of activator calcium from the SR. The possible i.c. modes of action are discussed as well as the idea that e.c. applied glycosides internalize and mediate inotropy via the i.e. mechanism.

  1. Profile of L-type Ca2+ current and Na+/Ca2+ exchange current during cardiac action potential in ventricular myocytes

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T.; Chen-Izu, Ye


    Objective The L-type Ca2+ current (ICa,L) and the Na+/Ca2+ exchange current (INCX) are major inward currents that shape the cardiac action potential (AP). Previously, the profile of these currents during AP was determined from voltage-clamp experiments that used Ca2+ buffer. In this study, we aimed to obtain direct experimental measurement of these currents during cardiac AP with Ca2+ cycling. Method A newly developed AP-clamp sequential dissection method was used to record ionic currents in guinea pig ventricular myocytes under a triad of conditions: using the cell’s own AP as the voltage command, using internal and external solutions that mimic the cell’s ionic composition and, importantly, no exogenous Ca2+ buffer was used. Results The nifedipine-sensitive current (INIFE), which is composed of ICa,L and INCX, revealed hitherto unreported features during AP with Ca2+ cycling in the cell. We identified two peaks in the current profile followed by a long residual current extending beyond the AP, coinciding with a residual depolarization. The second peak and the residual current become apparent only when Ca2+ is not buffered. Pharmacological dissection of INIFE using SEA0400 shows that ICa,L is dominant during phase-1&2 whereas INCX contributes significantly to the inward current at phase-3&4 of AP. Conclusion These data provide the first direct experimental visualization of ICa,L and INCX during cardiac AP and Ca2+ cycle. The residual current reported here can serve as a potential substrate for afterdepolarizations when increased under pathologic conditions. PMID:21884673

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

    Bassani R.A.


    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.

  3. 运动性心肌肥厚中PKC信号通路研究进展%Advance of PKC Signaling Pathway in Exercise -induced Cardiac Myocyte Hypertrophy

    柳华; 杨翼


    心肌肥厚是心脏受到刺激后的一种代偿反应。心肌的生理性肥厚可提高心脏机能,但病理性肥厚则会引起心血管疾病心律失常发病和死亡,亦是运动员发生猝死的原因之一。明确运动性心肌肥厚的机制,可为保护运动员心脏提供理论依据。目前为止,形成心肌肥厚的信号通路包括PKC、蛋白激酶B(Akt)、钙调神经磷酸酶(CaM)、丝裂原活化蛋白激酶MAPK、酪氨酸激酶受体gp130/STAT、牵拉敏感离子通道以及细胞骨架等。其中PKC途径是调控心肌细胞的生长、分化以及肥厚的过程中信号转导通路的关键环节。心肌细胞可通过Gq/PLC/Ca2+/PKC、PKC/MAPK、PKC/NF-κB等相关途径促使活化晚期反应基因使心肌肥厚。在运动过程中,形成的生理性肥厚主要通过AkffmTOR途径。心肌细胞的机械牵拉亦可以通过PKC信号传导促使肥厚。PKC包括13种亚型,各亚型对心脏的作用不一。PKCa对多次运动后心肌有保护作用;PKCβ1对心肌可能有保护作用,B2则是相反的作用;PKC8有利于心肌细胞的适应;PKCs对心肌的保护作用亦有可能有相反的作用;PKCζ促使心肌肥厚。%Myocardial hypertrophy is a compensatory response after the heart stimulation. Myocardial physio- logic hypertrophy can improve heart function, but pathological hypertrophy may cause cardiovascular disease as onset of arrhythmia and death, and also one of the causes of sudden death in athletes. The clearing mecha- nism of exercise -induced cardiac hypertrophy can provide a theoretical basis for the protection of athlete' s heart. So far, formation of myocardial hypertrophy signaling pathways includes PKC, protein kinase B ( Akt), calcineurin ( CaM), activation of the mitogen - activated protein kinase MAPK, tyrosine kinase re- ceptor gpl30/STAT, and the stretch of sensitive ion channels and cytoskeletal etc.. The PKC pathway is the

  4. Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure

    WANG Li-chun; ZENG Wu-tao; LIU Jun; DONG Yu-gang; TANG An-li; FENG Chong; MA Hong; HE Jian-gui; LIAO Xin-xue; CHEN Wen-fang; LENG Xiu-yu; MA Li; MAI Wei-yi; TAO Jun


    Background Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Results The fraction of cell shortening (FS%) and [Ca2+]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51±1.15 vs 13.21±1.49;[Ca2+]imax:330.85±50.05 vs 498.16±14.07; both P<0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/β-Actin: 0.51±0.12 vs 0.19±0.06, P<0.01; RPLB/β-Actin: 0.26±0.12 vs 0.20±0.08, P<0.05), while SERCA2 mRNA was downregulated (0.48±0.10 vs 0.80±0.11, P<0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P<0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141±0.047 and 1.074±0.081 times of that in PS group respectively (both P<0.05), and SERCA2 protein levels were 0.803±0.100 and 0.893±0.084 times of that in PS group respectively (both P<0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P<0.05).Conclusion ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

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

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


    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 α{sub 1} and α{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 α{sub 1} or α{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 μM) 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 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{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 α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

  6. Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

    Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A


    African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (Pchronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

  7. Contribution of sodium channel neuronal isoform Nav1.1 to late sodium current in ventricular myocytes from failing hearts

    Mishra, Sudhish; Reznikov, Vitaliy; Maltsev, Victor A; Undrovinas, Nidas A; Sabbah, Hani N; Undrovinas, Albertas


    Late Na+ current (INaL) contributes to action potential (AP) duration and Ca2+ handling in cardiac cells. Augmented INaL was implicated in delayed repolarization and impaired Ca2+ handling in heart failure (HF). We tested if Na+ channel (Nav) neuronal isoforms contribute to INaL and Ca2+ cycling defects in HF in 17 dogs in which HF was achieved via sequential coronary artery embolizations. Six normal dogs served as control. Transient Na+ current (INaT) and INaL in left ventricular cardiomyocytes (VCMs) were recorded by patch clamp while Ca2+ dynamics was monitored using Fluo-4. Virally delivered short interfering RNA (siRNA) ensured Nav1.1 and Nav1.5 post-transcriptional silencing. The expression of six Navs was observed in failing VCMs as follows: Nav1.5 (57.3%) > Nav1.2 (15.3%) > Nav1.1 (11.6%) > Nav2.1 (10.7%) > Nav1.3 (4.6%) > Nav1.6 (0.5%). Failing VCMs showed up-regulation of Nav1.1 expression, but reduction of Nav1.6 mRNA. A similar Nav expression pattern was found in samples from human hearts with ischaemic HF. VCMs with silenced Nav1.5 exhibited residual INaT and INaL (∼30% of control) with rightwardly shifted steady-state activation and inactivation. These currents were tetrodotoxin sensitive but resistant to MTSEA, a specific Nav1.5 blocker. The amplitude of the tetrodotoxin-sensitive INaL was 0.1709 ± 0.0299 pA pF–1 (n = 7 cells) and the decay time constant was τ = 790 ± 76 ms (n = 5). This INaL component was lacking in VCMs with a silenced Nav1.1 gene, indicating that, among neuronal isoforms, Nav1.1 provides the largest contribution to INaL. At –10 mV this contribution is ∼60% of total INaL. Our further experimental and in silico examinations showed that this new Nav1.1 INaL component contributes to Ca2+ accumulation in failing VCMs and modulates AP shape and duration. In conclusion, we have discovered an Nav1.1-originated INaL component in dog heart ventricular cells. This component is physiologically relevant to

  8. Simultaneous recording of ATP-sensitive K+ current and intracellular Ca2+ in anoxic rat ventricular myocytes. Effects of glibenclamide.

    Russ, U; Englert, H; Schölkens, B A; Gögelein, H


    We investigated the temporal relationship between the adenosine triphosphate-sensitive K current (KATP current), hypoxic shortening and Ca accumulation in cardiomyocytes exposed to anoxia or metabolic inhibition. Whole-cell, patch-clamp experiments were performed with nonstimulated isolated rat heart ventricular muscle cells loaded with the Ca-sensitive fluorescent dye 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'- amino-5'-methylphenoxy) ethane-N,N,N',N'-tetraacetic acid (fura-2) via the patch pipette. After approximately 8 min anoxia, the KATP current started to rise and reached a maximum of 21.3 +/- 3.7 nA (n = 5, recorded at 0 mV clamp potential) within 1-3 min. At that time hypoxic contracture also occurred. Resting cytoplasmic free calcium (Cai) did not change significantly before hypoxic shortening. After hypoxic contracture, the KATP current decreased and Cai started to rise, reaching about 1 micromol/l. The presence of glibenclamide (10 micromol/l) in the bath reduced the anoxia-induced KATP current by more than 50%, but did not significantly influence the time dependence of current, hypoxic shortening and Cai, or the magnitude of Cai. Metabolic inhibition with 1.5 mmol/l CN resulted in KATP current increase and hypoxic shortening, occurring somewhat earlier than under anoxia, but all other parameters were comparable. In non-patch-clamped cells loaded with fura-2 AM ester and field-stimulated with 1 Hz, 1 micronol/l glibenclamide had no significant effect on the magnitude of the Cai increase caused by exposure of the cells to 1.5 mmol/l CN-. After CN- wash-out in non-patch-clamped cells, Cai declined, oscillated and finally returned to control values. It can be concluded that glibenclamide inhibits anoxia-induced KATP currents only partially and has no significant effect on anoxia-induced rise in resting Cai.

  9. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)


    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  10. Sarcoplasmic reticulum calcium mobilization in right ventricular pressure-overload hypertrophy in the ferret: relationships to diastolic dysfunction and a negative treppe.

    Gwathmey, J K; Morgan, J P


    In a model of right-ventricular pressure-overload hypertrophy (POH) in the ferret, action potential duration (to 90% repolarization) was found to be significantly longer (228 +/- 11 vs 314 +/- 12 ms) with no change in amplitude (85 +/- 3 vs 85 +/- 2 mV) or resting membrane potential (-79 +/- 1.5 vs -79 +/- 1 mV) for control and POH, respectively. Peak sarcoplasmic reticulum Ca2+ release (expressed as the logarithm of the fractional luminescence, -4.2 +/- 0.1 vs -4.4 +/- 0.3) and resting calcium concentrations (-5.5 +/- 0.1 vs -5.7 +/- 0.1) were not different between the two groups (control vs POH respectively). Muscles from control and POH animals demonstrated a positive force/interval relationship in the presence of physiological extracellular [Ca2+]. However, unlike muscles from control animals, muscles from animals with POH subjected to increasing frequencies of contraction in the presence of increased extracellular [Ca2+] demonstrated further impairment of diastolic relaxation and a negative treppe. Exposure of muscles from POH animals to isoproterenol returned the slowed Ca2+ uptake by the sarcoplasmic reticulum as detected with aequorin to control values, although the relaxation phase of the isometric twitch remained prolonged compared to non-hypertrophied muscles. Exposure to milrinone also abbreviated the time course of the intracellular Ca2+ transient, but did not return it to that seen in normal myocardium. The exposure of non-hypertrophied isolated muscles to caffeine resulted in similar prolongation of the isometric twitch duration to that seen in hypertrophied myocardium. Results of these experiments suggest that impaired muscle relaxation in POH reflects changes at the level of the myofilaments. Thus, although slowed intracellular calcium mobilization contributes to diastolic relaxation abnormalities, it can not be the sole factor responsible for the slowed relaxation as has been suggested.

  11. Downregulation of Kv4.2 and Kv4.3 channel gene expression in right ventricular hypertrophy induced by monocrotaline in rat

    Tian-tai ZHANG; Bing CUI; De-zai DAI


    AIM: To investigate the differences in gene expression of transient outward potassium ion channel between the free wall of right ventricle, free wall of left ventricle, and the septum in monocrotaline (MCT)-induced right ventricular hypertrophy of rat. METHODS: Twenty rats were randomly divided into two groups: a single injection of monocrotaline (MCT) 60 mg/kg (model) or saline (control). Four weeks later, hemodynamic parameters were measured and the gene expression of Ito channels were detected by semi-quantitative RT-PCR. RESUITS: After 28 d, the right ventricular systolic pressure and central venous pressure were remarkably elevated by 128 % and 533 % in the MCT-treated group, accompanied by an overt right ventricle (RV) remodeling. The difference of mRNA expression of Kv1.4 was not significant in free wall of RV, left ventricle (LV), and septum in MCT group compared with control group. In contrast, mRNA of Ky4.2 and Ky4.3 in the free wall of RV in MCT-induced rat was dramatically decreased by 45.2 % and 51.1% vs control, however, in free wall of LV and septum, no difference was found. In addition, mRNA expression level of Ky4.2 in control rat was significantly lower in septum than that in free wall of RV and LV. CONCLUSION: Expression of Kv1.4. Ky4.2, and Kv4.3 differs between regions in normal rat hearts. The down-regulation of Ky4 family gene expression of Ito contributed to the pathophysiological changes in ventricular hypertrophy and pulmonary hypertension induced by MCT.

  12. Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway

    Rani, Shilpa; Sreenivasaiah, Pradeep Kumar; Cho, Chunghee; Kim, Do Han


    Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal (0.5 mg·kg−1·day−1) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling. PMID:28152298

  13. Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study

    Wachtell, K.; Palmieri, V.; Olsen, M.H.;


    in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow...

  14. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

    Hofgaard, Johannes P; Banach, Kathrin; Mollerup, Sarah


    Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesi...

  15. Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy

    WANG Shu-xia; HUI Ru-tai; FU Chun-yan; ZOU Yu-bao; WANG Hu; SHI Yi; XU Xi-qi; CHEN Jing-zhou; SONG Xiao-dong; HUAN Tu-jun


    Background Even carrying an identicai gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in Community based male subjects.The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM.Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for HCM.Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95% CI 1.01-1.77, P=0.04; OR 1.11, 95% CI 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95% CI 1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=O.04, respectively). No association was found between the two polymorphisms with female patients with HCM.Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.

  16. Transthoracic echocardiography in rats. Evalution of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging.

    Reffelmann, Thorsten; Kloner, Robert A


    Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-fa(cp) rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77-87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demonstrated by increased LV-mass-index (p rats.

  17. Localization of Kv4.2 and KChIP2 in lipid rafts and modulation of outward K+ currents by membrane cholesterol content in rat left ventricular myocytes.

    Rudakova, Elena; Wagner, Michael; Frank, Magdalena; Volk, Tilmann


    Lipid rafts are cholesterol-enriched microdomains of the cell membrane. Here we investigate the localization of the pore forming K(+)-channel α-subunit Kv4.2 and the β-subunit KChIP2, underlying the transient outward K(+) current (I to), in lipid rafts in left ventricular myocytes. Furthermore, we explored the impact of membrane cholesterol depletion (using 20 mM methyl-beta-cyclodextrin (MBCD)) on K(+) outward currents. Cholesterol-saturated MBCD (20 mM) served as control. Myocytes were isolated from the left ventricular free wall of Wistar rats. The Triton X-100 (4 °C) insoluble fraction of whole cell protein was analyzed by sucrose density gradient centrifugation followed by Western blot. Kv4.2 and KChIP2 were partially detected in low-density fractions (lipid rafts). MBCD treatment (5 min) resulted in a shift of Kv4.2 and KChIP2 towards high-density fractions. K(+) currents were assessed by whole-cell patch-clamp. MBCD treatment resulted in a 29 ± 3 % decrease in I to (20.0 ± 1.6pApF(-1) vs. 28.5 ± 2.0pApF(-1), n = 15, p lipid rafts. Membrane cholesterol depletion results in ~12 % net reduction of I to, a redistribution of the channel proteins Kv4.2 and KChIP2 and an increased delayed rectifier current.

  18. The value of the different indexes of electrocardiogram in diagnosing high blood pressure with left ventricular hypertrophy%心电图不同指标对高血压病左室肥厚的诊断价值

    严国平; 颜玉芳


    目的 探讨心电图(ECG)各指标对诊断高血压病左室肥厚(LVH)的价值.方法 根据超声心动图(UCG)报告,确定观察组(A组)高血压病伴LVH 55例及对照组(B组)高血压病不伴LVH 50例;测定ECG各指标数据并计算其敏感性.结果 ECG不同指标对诊断高血压病LVH的价值存在较大差异,其中QRS波群电压指标敏感性最高,肢体导联室壁激动时间(VAT)次之,余指标敏感性较低.结论 ECG不同指标在诊断高血压病LVH时的价值不同.%Objective To investigate the value of the different indexes of electrocardiogram (ECG) in diagnosing high blood pressure with left ventricular hypertrophy. Methods 55 cases of high blood pressure with left ventricular hy-pertrophy and 50 cases of high blood pressure without left ventricular hypertrophy by the investigation of ultrasonic cardio-gram(UCG) were studied. The figure and sensitivity of the different indexes of ECG were determined. Results There was obvious difference among each ECG index in the diagnosing value of high blood pressure with left ventricular hypertro-phy, QRS wave amplitude had the most sensitive value compared with others. Conclusion It was different for each ECG index in the value of diagnosing high blood pressure with left ventricular hypertrophy. In order to improve the diagnosing ac-curacy, it is important to understand the different diagnosing value of each ECG index.

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

    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


    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 μm, P 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 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 μm/s, P 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.

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

    Hakalahti Anna E


    Full Text Available Abstract Background The beta-1 adrenergic receptor (β1AR 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 β1AR 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

  1. T-wave inversions related to left ventricular basal hypertrophy and myocardial fibrosis in non-apical hypertrophic cardiomyopathy: A cardiovascular magnetic resonance imaging study

    Chen, Xiuyu, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Shihua, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Tao, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Lu, Minjie, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Yin, Gang, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jiang, Shiliang, E-mail: [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Prasad, Sanjay, E-mail: [NIHR Biomedical Research Unit, Royal Brompton Hospital Sydney Street, London, SW3 6NP (United Kingdom)


    Objectives: To investigate the relationship between T-wave inversions and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in patients with non-apical hypertrophic cardiomyopathy (HCM). Methods: 196 consecutive patients with non-apical HCM underwent late gadolinium enhancement (LGE) CMR and 12-lead electrocardiogram. The distribution and magnitude of LV segmental hypertrophy and LGE were assessed according to the AHA 17-segment model and analyzed in relation to T-wave inversions. Results: Of 196 HCM patients, 144 (73%) exhibited T-wave inversions. 144 (73%) patients had evidence of myocardial fibrosis as defined by LGE, and the prevalence of LGE was significantly higher in patients with T-wave inversions compared with those without T-wave inversions (78% vs. 59%, P = 0.008). T-wave inversions were related to basal anterior and basal anteroseptal LGE (20% vs. 10%, P = 0.04 and 68% vs. 46%, P = 0.005, respectively). In addition, T-wave inversions were associated with greater basal anteroseptal and basal inferior wall thickness (19.5 ± 4.7 mm vs. 16.7 ± 4.5 mm, P < 0.001 and 10.9 ± 3.3 mm vs. 9.6 ± 3.0 mm, P = 0.01, respectively). By logistic regression analysis, basal anteroseptal wall thickness and LGE were independent determinants of T-wave inversions (P = 0.005, P = 0.01, respectively). Conclusions: T-wave inversions in HCM are associated with LGE and wall thickness of the left ventricular basal segments. Moreover, basal anteroseptal wall thickness and LGE are independent determinants of T-wave inversions.

  2. Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation

    Huang, Wei-Lin; Chou, Shih-Jie; Chang, Wei-Chao; Chang, Yuh-Lih; Leu, Hsin-Bang; Chen, Kuan-Hsuan; Wang, Kang-Ling; Lai, Ying-Hsiu; Liu, Yung-Yang; Lu, Kai-Hsi; Li, Hsin-Yang; Sung, Yen-Jen; Jong, Yuh-Jyh; Chen, Yann-Jang; Chen, Chung-Hsuan; Yu, Wen-Chung


    Rationale A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. Objective Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. Results and methods The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients’ sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. Conclusion Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation. PMID:27888626

  3. IGF-1 response to arm exercise with eccentric and concentric muscle contractions in resistance-trained athletes with left ventricular hypertrophy.

    Żebrowska, A; Waśkiewicz, Z; Zając, A; Gąsior, Z; Galbo, H; Langfort, J


    The study aimed at evaluating changes in plasma levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), testosterone, growth hormone (GH), cortisol, and insulin in resistance-trained male athletes with (n=9) and without (n=9) left ventricular hypertrophy (LVH) in response to eccentric (ECC) and concentric (CON) arm exercise. 10 age-matched healthy non-trained subjects served as controls. M-mode and 2D Doppler echocardiography were used to estimate LV mass.Resting IGF-1 concentration was higher in LVH athletes compared to controls (52 ± 5 nM vs. 46 ± 7 nM, pexercise resulted in higher (pexercise resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242 ± 57 and 274 ± 58, athletes, vs. 215 ± 63 and 244 ± 67, controls, nM, pexercise, GH concentrations were lower in LVH than in non-LVH athletes (4.7 ± 2.1 vs. 6.1 ± 1.8 ng  mL(-1), peccentric arm exercise. These findings suggest a role of IGF-1, possibly released from contracting muscle, in stimulating LV hypertrophy in resistance training.

  4. Reduction of prohibitin expression contributes to left ventricular hypertrophy via enhancement of mitochondrial reactive oxygen species formation in spontaneous hypertensive rats.

    Zheng, H; Lu, G M


    Left ventricular hypertrophy (LVH) in hypertension is characterized by thickening of myocardium and decrease in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. In this work, we investigate whether mitochondrial prohibitin (PHB) was involved in the progression of LVH in spontaneous hypertensive rats (SHR). First, it was found that mitochondrial dysfunction occurred in left ventricles of SHR. Through analysis using quantitative reverse transcription polymerase chain reaction and Western blotting, it was found that PHB mRNA and mitochondrial PHB levels in left ventricles of SHR were significantly lower than that in Wistar-Kyoto rats. Furthermore, PHB mRNA levels were negatively correlated to left ventricles weight-to-body weight ratio in SHR. Knockdown of PHB led to increased formation of mitochondrial reactive oxygen species (ROS) and reduced activities of complex I, mitochondrial adenosine triphosphate generation and mitochondrial membrane potential in cultured cardiomyocytes. Knockdown of PHB contributed to the cardiomyocyte hypertrophy, which could be attenuated by treatment with the Tempol. Angiotensin II (AngII) was increased in plasma and left ventricles of SHR. Incubation with AngII reduced mitochondrial PHB expression in cardiomyocytes, which was reversed when pretreated with losartan. In conclusion, reduction of PHB expression in left ventricles in SHR contributed to LVH, at least in part, through promoting mitochondrial ROS formation.

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

    Zahra Alizadeh-Sani


    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.

  6. Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways.

    Shi, Liang; Xu, Hao; Wei, Jinhong; Ma, Xingfeng; Zhang, Jianbao


    Caffeine is commonly utilized to trigger intracellular calcium in cardiomyocyte. It is well accepted that caffeine could induce cardiac arrhythmia, but it is not clear with regard of its impacts on the cardiac function. This article presents a recent study concerning the effects of caffeine on the cardiomyocyte hypertrophy and the associated signal pathway. The experimental results showed that the total protein contents, the surface area of cardiomyocyte and β-myosin heavy chain (β-MHC) expression increased in ventricular myocytes of neonatal Sprague-Dawley (SD) rats after 24h caffeine incubation. It is also observed that the basal intracellular calcium (Ca(2+)) level has increased, while the amplitude of Ca(2+) oscillation and Ca(2+) content have decreased in sarcoplasmic reticulum (SR). The caffeine-induced myocyte enhancer factor-2 (MEF2) expression and hypertrophy can be completely abolished by the inhibition of cardiac ryanodine receptor (RyR2), as well as KN93 and curcumin treatments. Meanwhile, the amplitude of Ca(2+) oscillation and the Ca(2+) content of SR in the completely-inhibited group have reached the physiological level. These results suggest that the caffeine-induced cardiomyocyte hypertrophy established the connection between Ca(2+) release from SR and cytosol that activates CaMKII and p300, which in turn enhances the expression of MEF2 that promotes cardiomyocyte hypertrophy.

  7. Generation of PP2A CαKnockout Model in Neonatal Mouse Ventricular Myocytes%PP2A Cα敲除小鼠心肌细胞模型的构建

    陈文; 温明达; 董大川; 高艳红; 张朝


    To generate PP2A Cαknockout model in neonatal mouse ventricular myocytes. Male PP2A Cαfl/fl,Cre/-were se-lectively mated with female PP2A Cαfl/fl,Cre/- mice to obtain abundant offsprings with the same genotype. The neonatal mouse ventricular myocytes were digested by trypsinization and subsequently infected with Cre-adenovirus. The effects of adenovirus infection were observed by fluorescence microscope and identified by western blot analysis. The offsprings in aboundance were obtained by seting up a mating between male and female of PP2A Cαfl/fl,Cre/-mice, as a result, an abundance of neonatal mouse ventricular myocytes with the genotype of PP2A Cαfl/fl,Cre/-were available for Ad-Cre infection. Green fluorescence was observed after GFP labeled Cre-adenovirus( Cre-Ad) infection for 48 h. The expression level of PP2A Cα protein in Cre-Ad infected myocytes was 60% ~80% lower than control. The PP2A Cα knockout model in neonatal mouse ventricular myocytes was successfully generated.%体外构建PP2A Cα敲除的原代小鼠心室肌细胞模型。选择性地将雄性PP2A Cαfl/fl,Cre/-小鼠与雌性PP2A Cαfl/fl,Cre/-小鼠交配。新生小鼠心脏经胰酶消化后差速贴壁获得原代小鼠心室肌细胞,用带有Cre的腺病毒侵染心肌细胞,经荧光显微镜观察和Western-blot检测,分析PP2A Cα的敲除效果。将基因型为PP2A Cαfl/fl,Cre/-的雌雄小鼠进行交配,得到其同样基因型的后代,进而可获得足量基因型为PP2A Cαfl/fl,Cre/-的原代小鼠心肌细胞。用带有重组酶Cre的腺病毒侵染细胞48 h后,可见带有绿色荧光的心肌细胞;Western-blot检测显示,PP2A Cα在Cre腺病毒侵染的心肌细胞可下调60%~80%。本研究成功建立了PP2A Cα敲除的原代小鼠心肌细胞模型。


    S. N. Tolpygina


    Full Text Available Aim. To compare the effects of long-term therapy with angiotensin-II receptor antagonist losartan, alone or in combination with hydrochlorothiazide, and amlodipine treatment on left ventricular morpho-functional variables and blood pressure (BP in hypertensive patients.Material and methods. 25 women and 27 men (average age 52,7±1,2 y.o. with essential hypertension (1-2 grade and left ventricular hypertrophy (LVH were included into the study. After 3 week washout period the patients were randomized in 2:1 fashion to receive either losartan (n=34 or amlodipine (n=17. In 17 patients with insufficient response to losartan monotherapy (50-100mg/day hydrochlorothiazide (12,5mg was added to losartan (50mg 4 weeks later. The daily dose of amlodipine was increased from 5 to 10 mg in 10 patients. At baseline and after 24 weeks of treatment 24-h BP monitoring and echocardiography (with evaluation of cardiac chamber dimensions, inter-ventricular septal and posterior wall thickness, left ventricular mass index -LVMI were performed.Results. 4-week losartan treatment significantly decreased clinic BP (-14,1±2,2/8,2±1,4 mm Hg, p<0,01, mean daily systolic and diastolic BP (-15,1±2,4 mm Hg and -8,9±1,7 mm Hg , p<0,001, mean day-time and night-time BP and systolic and diastolic BP load in 34 patients. Addition of hydrochlorothiazide induced a further decrease of mean night-time BP, pulse BP, improved circadian rhythm and normalized BP in 75% of patients compared with 50% in losartan alone. Significant decrease of clinic BP (-24,1±3,6/15,2±2,3, p<0,01, mean daily systolic and diastolic BP and BP load were noticed at 24 week of amlodipine treatment. Circadian BP rhythm didn’t change; night-time decrease of BP was insufficient. Antihypertensive efficacy was similar in both groups. Losartan, alone or combined with hydrochlorothiazide, caused regression of LVH in all patients, normalized geometry of left ventricle in 33% of patients and improved left

  9. 乙酰胆碱对离体豚鼠心室肌的直接作用机制探讨%The mechanisms underlying the effects of acetylcholine on isolated guinea-pig ventricular myocytes

    方萍; 张晓东; 等


    To investigate the mechanisms underlying the effects of ACh on isolated guinea-pig ventricular myocytes. METHODS: Using standard microelectrodes and force transducer we recorded the effects of ACh (10-5 mol/L) and various blockers such as atropine, CsCl and CdCl2 on the action potential and force contraction in isolated ventricular myocytes of guinea-pig. RESULTS: ACh(10-5 mol/L) reduced the duration of action potential and twitch tensions by 7.31% and 37.57% respectively (P<0.05),which could be blocked by atropine, CsCl, but not by CdCl2. CONCLUSION: ACh (10-5 mol/L) could cause a negative chronotropic and inotropic effects on guinea-pig ventricular myocytes. These effects are related to the muscarinic receptor and the potassium channel and may not related to the calcium channel.%目的: 研究乙酰胆碱(ACh)对离体豚鼠心室肌的直接负性作用及机制。方法: 采用标准玻璃微电极细胞内记录技术记录动作电位(AP)及肌力换能器记录心肌收缩力(FC)的方法观察ACh对离体豚鼠心室肌的作用,并观察几种受体或通道水平的阻断剂阿托品、氯化铯(CsCl)、氯化镉(CdCl2)对ACh直接作用的影响。结果: 10-5mol/L ACh对心室肌动作电位持续时间(APD)及FC的抑制率分别为7.31%和37.57%(P<0.05),10-5 mol/L阿托品和20 mmol/L CsCl可阻断该作用,0.1 mmol/L CdCl2对该作用无影响。结论: 10-5mol/L ACh 对离体豚鼠心室肌有直接负性作用,ACh的作用与毒蕈碱型胆碱受体及K+电流有关,而与Ca2+电流的关系可能不大。

  10. E-4031 enhanced Ca2+ transient and ventricular myocytes contraction via reverse mode Na+/Ca2+ exchange in normal and hypertrophic rats%E-4031通过反向钠钙交换增加正常和心肌肥厚大鼠心肌细胞钙瞬变和收缩

    崔香丽; 赵录英; 吴博威


    AIM: To study the effects of N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]methanesulfonamide dihydrochloride dihydrate (E-4031), a specific Ikblocker, on Ca2+ transient and cell contractionof normal and hypertrophied rat ventricular myocytes. METHODS: Electrically triggered Ca2+ transient and cellshortening were measured simultaneously using the Ion Imaging System with charge coupled digital (CCD) camera.REESULTS: E-4031 (10μmol/L) increased Ca2+ transient and cell shortening from (210+49) and (3.0-x-0.8) Um to(245±47) and (3.6+1.0) μm, respectively (P<0.05) in normal cardiomyocytes and from (196±54) and (3.0+1.3)μm to (240-±49) and (3.6+1.3) μm respectively (P<0.05) in hypertrophied cardiomyocytes, while did not changecalcium sensitivity in both groups. KB-R7943 completely blocked the activating effects induced by E-4031 in bothof normal and hypertrophied cardiomyocytes. Nicardipine did not block the increasing effects of E-4031.CCONCLUSION: E-4031 increased Ca2+ transient and cell contraction via stimulating reverse mode of Na+/Ca2+exchange while without influencing calcium sensitivity. These effects were more notable in hypertrophiedcardiomyocytes than in normal myocytes.%目的:观察Ik阻断剂E一4031对正常和心肌肥厚大鼠钙瞬变和细胞收缩的影响.方法:应用带CCD Cam-era的离子影象分析系统(Ion Imaging System)测定离体大鼠心肌细胞钙瞬变和细胞长度.结果:E-4031(10Umol/L)分别使正常组钙瞬变和细胞缩短从对照组的(210±49)和(3.0±0.8)u皿增加到(245±47)和(3.6±1.0)um(P<0.05),使心肌肥厚组钙瞬变和细胞缩短分别从对照组的(196±54)和(3.0±1.3)um增加到(240±49)和(3.6±1.3)um(p<0.05),而对钙敏感性无显著影响.KB-R7943可完全阻断正常组和肥厚组心肌细胞由E-4031诱导的激动作用.尼卡地平不能阻断E-4031的增加作用.结论:E一4031可通过刺激反向钠钙交换增加正常和心肌肥厚大鼠心肌细胞钙瞬变

  11. Vitamin D therapy to reduce blood pressure and left ventricular hypertrophy in resistant hypertension: randomized, controlled trial.

    Witham, Miles D; Ireland, Sheila; Houston, J Graeme; Gandy, Stephen J; Waugh, Shelley; Macdonald, Thomas M; Mackenzie, Isla S; Struthers, Allan D


    Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on ≥3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 42 (16) nmol/L. Treatment with vitamin D did not reduce 24-hour ambulatory blood pressure (adjusted treatment effects: systolic, +3 mm Hg; 95% confidence interval, -4 to +11; P=0.33; diastolic, -2 mm Hg; 95% confidence interval, -6 to +2; P=0.29); similar results were seen for office blood pressure. Left ventricular mass index was measured in a subgroup (n=25); no reduction was seen with vitamin D treatment (adjusted treatment effect, +4 g/m(2); 95% confidence interval, 0 to +7; P=0.04). There was no significant change in cholesterol or glucose levels. Thus, 6 months of intermittent, high-dose oral vitamin D3 did not reduce blood pressure or left ventricular mass in patients with resistant hypertension.

  12. The Relationship Between Increased Epicardial Fat Thickness and Left Ventricular Hypertrophy and Carotid Intima-Media Thickness in Patients With Nonfunctional Adrenal Incidentaloma



    Full Text Available Background Emerging evidences indicate that patients diagnosed with Adrenal Incidentaloma (AI may present cardiovascular complications. Epicardial fat thickness (EFT has recently been described as a new risk factor and an active player in metabolic syndrome and cardiovascular disease. Objectives We aimed to evaluate the relationship between EFT and left ventricular hypertrophy and carotid intima-media thickness, which are both strong predictors of cardiovascular morbity and mortality, in patients with nonfunctioning AI. Patients and Methods We evaluated 51 patients (36 females and 15 males diagnosed with AI and 35 (29 females, 6 males age, gender and body mass index (BMI matched healthy controls in terms of cardiovascular risk parameters. Epicardial fat was identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium. Results Epicardial fat thickness was significantly higher in patients with AI when compared to the control group (0.89 ± 0.32 cm vs. 0.74 ± 0.26 cm; P = 0.023. left ventricular (LV mass index and median carotid intima-media thickness (CIMT were also higher in subjects with AI than in controls (99.8 g/m2 vs. 86.9 g/m2; P = 0.024 and 7.5 mm (5.5 - 11.5 vs. 6.5 mm (4.5 - 9.5; P = 0.017. There was a positive correlation between EFT, LV mass index, EFT and CIMT (r = 0.315, P = 0.004; r = 0.363, P < 0.001; respectively. Conclusions In this study we showed that EFT, measured by echocardiography is higher in subjects with AI when compared to healthy controls. epicardial fat thickness had the best independent correlation with AI in multiple logistic regression analysis. Incidentaloma is also associated with increased left ventricular mass index and CIMT. Adrenal incidentaloma patients may show early cardiac changes, such as increased left ventricular mass and increased CIMT.

  13. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    Trimarchi Francesco


    Full Text Available Abstract Background Most patients with growth hormone deficiency (GHD show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. Methods Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8% were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2 and relative wall thickness (cut-off 0.45 at echocardiography. Results There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD and in 15% of controls (p = NS. Conclusion Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy, not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials.

  14. Degree and distribution of left ventricular hypertrophy as a determining factor for elevated natriuretic peptide levels in patients with hypertrophic cardiomyopathy: insights from cardiac magnetic resonance imaging.

    Park, Jeong Rang; Choi, Jin-Oh; Han, Hye Jin; Chang, Sung-A; Park, Sung-Ji; Lee, Sang-Chol; Choe, Yeon Hyeon; Park, Seung Woo; Oh, Jae K


    Whether the left ventricular (LV) mass index (LVMI) and LV volumetric parameters are associated independently with natriuretic peptide levels is unclear in hypertrophic cardiomyopathy (HCM). Therefore, we investigated which parameters have an independent relationship with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in HCM patients using echocardiography and cardiac magnetic resonance imaging (CMR). A total of 103 patients with HCM (82 men, age 53 ± 12 years) were evaluated. Echocardiographic evaluations included left atrial volume index (LAVI) and early diastolic mitral inflow E velocity to early annular Ea velocity ratio (E/Ea). LVMI, maximal wall thickness and LV volumetric parameters were measured using CMR. The median value of NT-proBNP level was 387.0 pg/ml. The mean NT-proBNP level in patients with non-apical HCM (n = 69; 36 patients with asymmetric septal hypertrophy, 11 with diffuse, and 22 with mixed type) was significantly higher than in those with apical HCM (n = 34, P < 0.001). NT-proBNP level was negatively correlated with LV end-diastolic volume (LVEDV) (r = -0.263, P = 0.007) and positively with LVMI (r = 0.225, P = 0.022) and maximal wall thickness (r = 0.495, P < 0.001). Among the echocardiographic variables, LAVI (r = 0.492, P < 0.001) and E/Ea (r = 0.432, P < 0.001) were correlated with NT-proBNP. On multivariable analysis, non-apical HCM, increased maximal wall thickness and LAVI were independently related with NT-proBNP. Severity of LV hypertrophy and diastolic parameters might be important in the elevation of NT-proBNP level in HCM. Therefore, further evaluation of these parameters in HCM might be warranted.

  15. Kinetic mRNA Profiling in a Rat Model of Left-Ventricular Hypertrophy Reveals Early Expression of Chemokines and Their Receptors

    Nemska, Simona; Monassier, Laurent; Gassmann, Max; Frossard, Nelly; Tavakoli, Reza


    Left-ventricular hypertrophy (LVH), a risk factor for heart failure and death, is characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and leukocyte infiltration. Chemokines interacting with G protein-coupled chemokine receptors may play a role in LVH development by promoting recruitment of activated leukocytes or modulating left-ventricular remodeling. Using a pressure overload-induced kinetic model of LVH in rats, we examined during 14 days the expression over time of chemokine and chemokine receptor mRNAs in left ventricles from aortic-banded vs sham-operated animals. Two phases were clearly distinguished: an inflammatory phase (D3-D5) with overexpression of inflammatory genes such as il-1ß, tnfa, nlrp3, and the rela subunit of nf-kb, and a hypertrophic phase (D7-D14) where anp overexpression was accompanied by a heart weight/body weight ratio that increased by more than 20% at D14. No cardiac dysfunction was detectable by echocardiography at the latter time point. Of the 36 chemokines and 20 chemokine receptors analyzed by a Taqman Low Density Array panel, we identified at D3 (the early inflammatory phase) overexpression of mRNAs for the monocyte chemotactic proteins CCL2 (12-fold increase), CCL7 (7-fold increase), and CCL12 (3-fold increase), for the macrophage inflammatory proteins CCL3 (4-fold increase), CCL4 (2-fold increase), and CCL9 (2-fold increase), for their receptors CCR2 (4-fold increase), CCR1 (3-fold increase), and CCR5 (3-fold increase), and for CXCL1 (8-fold increase) and CXCL16 (2-fold increase). During the hypertrophic phase mRNA expression of chemokines and receptors returned to the baseline levels observed at D0. Hence, this first exhaustive study of chemokine and chemokine receptor mRNA expression kinetics reports early expression of monocyte/macrophage-related chemokines and their receptors during the development of LVH in rats, followed by regulation of inflammation as LVH progresses. PMID:27525724

  16. A Rare Case of Lipomatous Hypertrophy of the Interventricular Septum

    Papadopoulos, Christodoulos E.; Matsiras, Sotirios; Vassilikos, Vassilios


    Asymmetrical left ventricular hypertrophy secondary to interventricular septum hypertrophy is usually considered a typical phenotype of hypertrophic cardiomyopathy. In rare cases other conditions such as tumors or lipomatous hypertrophy of the interventricular septum may have a similar presentation. We present a case of a male patient who presented for routine cardiology work up and was diagnosed of having ventricular septal hypertrophy secondary to localized lipomatous hypertrophy.

  17. Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle.

    Py, Guillaume; Eydoux, Nicolas; Lambert, Karen; Chapot, Rachel; Koulmann, Natahlie; Sanchez, Hervé; Bahi, Lahoucine; Peinnequin, André; Mercier, Jacques; Bigard, André-Xavier


    To dissect the independent effects of altitude-induced hypoxemia and anorexia on the capacity for cardiac lactate metabolism, we examined the effects of 21 days of chronic hypobaric hypoxia (CHH) and its associated decrease in food intake and right ventricle (RV) hypertrophy on the monocarboxylate transporter 1 and 4 (MCT) expression, the rate of lactate uptake into sarcolemmal vesicles, and the activity of lactate dehydrogenase isoforms in rat muscles. In comparison with control rats (C), 1 mmol/L lactate transport measured on skeletal muscle sarcolemmal vesicles increased by 33% and 58% in hypoxic (CHH, barometric pressure = 495 hPa) and rats pair-fed an equivalent quantity of food to that consumed by hypoxic animals, respectively. The increased lactate transport was higher in PF than in CHH animals ( P < .05). No associated change in the expression of MCT1 protein was observed in skeletal muscles, whereas MCT1 mRNA decreased in CHH rats, in comparison with C animals (42%, P < .05), partly related to caloric restriction (30%, P < .05). MCT4 mRNA and protein increased during acclimatization to hypoxia only in slow-oxidative muscles (68%, 72%, P < .05, respectively). The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction. In both the left and right ventricles, the MCT1 protein content was unaffected by ambient hypoxia or restricted food consumption. These results suggest that MCT1 and MCT4 gene expression in fast-glycolytic muscles is mainly regulated by posttranscriptional mechanisms. Moreover, the results emphasize the role played by caloric restriction on the control of gene expression in response to chronic hypoxia and suggest that hypoxia-induced right ventricle hypertrophy failed to alter MCT proteins.

  18. Effect of Tanshinone Ⅱ -A on L-type calcium channel in rat ventricular myocytes%丹参Ⅱ-A对大鼠心肌细胞L-型钙通道的影响 

    黄健; 裴娟慧; 滕思勇; 郝杰; 张银辉; 浦介麟; 惠汝太


    目的 研究丹参酮Ⅱ-A对大鼠心肌细胞L型钙通道的影响.方法 采用酶解法制备大鼠心肌细胞,应用全细胞膜片钳技术检测大鼠心肌细胞L-型钙通道的电流密度和动力学.结果 丹参酮Ⅱ-A对L-型钙通道有抑制作用.在0μmol/L、10 μmol/L、20μmol/L和40μmol/L丹参酮Ⅱ-A作下,L-型钙通道的峰值电流密度分别为-13.34±1.06 pA/pF、-10.46 ±0.75 pA/pF、-7.62±0.50 PA/pF和-4.69±0.18 PA/pF,其抑制率分别为28.40%、52.14%和73.50% (n=8,P<0.05).结论 丹参酮Ⅱ-A抑制大鼠心肌细胞L-型钙通道,降低L-型钙通道的电流密度,呈浓度依赖性.%Objective To investigate the effect of Tanshinone Ⅱ -A on L-type calcium channel in isolated rat ventricular myocytes. Methods rat ventricular myocytes were isolated by enzymatic method, whole cell patch clamp technique was used to record the current and gating. Result Tanshinone Ⅱ-A inhibit L-type calcium channel current density. Tanshinone Ⅱ -A at μmol/L, 10μmol/L, 20μmol/L and 40 μmol/L,peak L-type calcium channel current density(Ica-L) were -13.34± 1.06 pA/pF, -10.46±0.75 pA/pF, -7.62±0.50 pA/pF and -4.69 ±0.18 pA/pF respectively, the inhibition rates were 28.40%, 52.14% and 73.50% respectively (n=8,P<0.05). Conclusion Effect of Tanshinone Ⅱ-A on rat cardiac myocytes L-type calcium current was significantly inhibited.


    傅丽英; 李泱; 夏国瑾; 姚伟星; 江明性


    目的研究4-氨基吡啶(4-AP)对心肌细胞L型钙通道和钠通道的影响。方法用全细胞膜片钳技术考察4-AP对豚鼠心室肌细胞L型钙电流和钠电流的作用。结果 4-AP 0.1, 0.5, 1.0 mmol*L-1浓度依赖性地抑制L型钙电流(ICa,L)和钠电流(INa),抑制率分别为(11.6±1.7)%,(37.5±8.3)%和(54.5±6.9)%以及(22.1±14.3)%,(39.4±8.8)%和(62.3±6.8)%。0.5 mmol*L-1 4-AP使ICa,L和INa I-V曲线均上移。结论 4-AP可浓度依赖性地阻滞豚鼠心室肌细胞L型钙通道和钠通道。%AIM To investigate the effect of 4-aminopyridine (4-AP) on ion channels of myocytes. METHODS L-type calcium channel and sodium channel currents were recorded in guinea pig single ventricular myocyte using whole-cell patch-clamp techniques. RESULTS 4-AP, 0.1, 0.5 and 1.0 mmol*L-1 were shown to inhibit L-type calcium channel currents (ICa,L) and sodium channel currents (INa) concentration-dependently. The percentage of inhibition were (11.6±1.7)%, (37.5±8.3)% and (54.5±6.9)% (P<0.01) respectively for ICa,L, and (22.1±14.3)% (P<0.05), (39.4±8.8)% and (62.3±6.8)% (P<0.01) respectively for INa. 4-AP 0.5 mmol*L-1 shifted the I-V curves of ICa,L and INa upwardly. CONCLUSION 4-AP blocked L-type calcium channel and sodium channels in guinea-pig ventricular myocytes concentration-dependently.

  20. Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes%肿瘤坏死因子α对大鼠心室肌细胞钙转运的影响

    李小强; 招明高; 梅其柄; 张延凤; 曹蔚; 王海芳; 陈丹; 崔毅


    AIM: To study the effects of tumor necrosis factor-alpha (TNF-α) on calcium movement in rat ventricular myocytes. METHODS: Intracellular free Ca2+ concentration was measured with calcium fluorescent probe Fluo-3/AM and laser confocal microscope. L-type calcium current (Ica,L) was recorded with the whole-cell configuration of the patch-clamp techniques. RESULTS: At 2, 20 and 200 μg/L, TNF-α was found to increase intracellular free Ca2+ concentration in a dose-dependent manner illustrated by the increment of calcium fluorescence density with laser confocal microscope. Nicardipine 0.5 μmol/L slightly attenuated TNF-α-induced response. When the cardiac myocytes were exposed to caffeine (100 mmol/L) for 30 min, TNF-α failed to induce any change of intracellular free calcium. However, it was found that TNF-α inhibited Ica,L in whole-cell patch-clamp experiments. At 2, 20, and 200 μg/L, TNF-α decreased peak Ica,L by 3.9 % (-5.1 pA/pF+0.3 pA/pF vs -4.9 pA/pF+0.2 pA/pF, n=9, P>0.05), 15.7 % (-5.1 pA/pF+0.3 pA/pF vs -4.3 pA/pF+0.3 pA/pF, n=9, P<0.05) and 19.6 % (-5.1 pA/pF+0.3 pA/ pF vs -4.1 pA/pF+0.4 pA/pF, n=9, P<0.01), respectively. It shifted the steady-state inactivation curve of Ica,L to the left (V1/2 shifted from -28.7 mV+0.3 mV to -37.8 mV+1.4 mV, n=7, P<0.05), while it took no effects on steadystate activation and recovery from inactivation. CONCLUSION: TNF-α inhibited Ica,L in rat ventricular myocytes,while increasing the intercellular free Ca2+ level due to the release of Ca2+ from intracellular stores.

  1. Fast diastolic swinging motion of the mitral valve as a clinical marker of familial hypertrophic cardiomyopathy in genetically affected young children without left ventricular hypertrophy: a new role for noninvasive imaging?

    Udink ten Cate, Floris E A; Junghaenel, Shino; Brockmeier, Konrad; Sreeram, Narayanswami


    Structural mitral valve (MV) abnormalities are common in patients with hypertrophic cardiomyopathy (HCM). This is the first report demonstrating MV abnormalities in very young children as the sole overt clinical feature of a known HCM-causing sarcomere protein gene mutation. Due to MV leaflet elongation, we also noticed a typical fast diastolic swinging motion of the MV in our patients. This novel echocardiographic feature may be used as a clinical marker of HCM disease in the absence of left ventricular hypertrophy.


    A. N. Zakirova


    Full Text Available Aim. To assess the role of the activation of matrix metalloproteinase-1 zymogen (ProMMP-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in the development of left ventricular (LV hypertrophy in patients with arterial hypertension (HT and metabolic syndrome (MS with varying degree of obesity.Material and methods. 108 patients with HT and MS divided into 3 groups according to body mass index, and 28 healthy women were studied. Intracardiac blood flow and ProMMP-1 and TIMP-1 levels were assessed.Results. Disbalance in the ProMMP-1 and TIMP-1 systems  is associated with the severity of left ventricular remodeling and grade of obesity. The changes in LV structure and geometry and activation ProMMP-1 with a deficit of TIMP-1 were most significant in patients with HT and grade 3 obesity (respectively 7.7±0.61 and 183.6±17.2 ng/ml in grade 3 obesity vs 3.5±0.3 and 291.7±22.4 ng/ml in grade 1 obesity; p<0.05. Associations between hemodynamic parameters and levels of ProMMP-1 [withLVmass index (LVMI: r=0.47; p<0.05] and TIMP-1 (with LVMI: r=-0.39;  p<0.05 were determined.Conclusion. Changes in the ProMMP-1 and TIMP-1 system in women with HT and MS are associated with the severity ofLVhypertrophy.

  3. Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease.

    Dong, Hao-jian; Huang, Cheng; Luo, De-mou; Ye, Jing-guang; Yang, Jun-qing; Li, Guang; Luo, Jian-fang; Zhou, Ying-ling


    Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.


    Denesiuk, E V


    The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology.

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

    Tasić Ivan


    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

  6. Effects of Yixin Jiangya Capsules on Insulin Resistance and Tumor Necrosis Factor-α in Cases of Primary Hypertension with Left Ventricular Hypertrophy

    Duan Xuezhong; Zhong Shenqing; Sun Xiqing; Cai Xinji


    Objectives:To observe the effects of Yixin Jiangya Capsules (益心降压胶囊 capsules for nourishing the heart and lowering blood pressure) on insulin resistance (IR) and tumor necrosis factor-α (TNF-α) in patients with primary hypertension with left ventricular hypertrophy (LVH). Methods: Totally 93cases were randomly divided into a control group of 31 cases taking Enalapril and a treatment group of 62cases taking Enalapril and Yixin Jiangya Capsules. Results: Fasting serum insulin (FSI) and TNF-α obviously increased and insulin sensitive index (ISI) significantly decreased in both groups before treatment as compared to those of a healthy group. After treatment, FSI, TNF-α and fasting blood glucose (FBG) obviously decreased and ISI remarkably increased in the treatment group, while ISI significantly increased and TNF-α obviously decreased in the control group. The curative effect in the treatment group was remarkably superior to that in the control group. FSI was positively related to TNF-α before treatment in both groups. Conclusion: FSI and TNF-α obviously increase and ISI significantly decreases in patients with primary hypertension with LVH. FSI and TNF-α influencing each other are involved in the generation and development of hypertension. Yixin Jiangya Capsules can improve IR and decrease TNF-α.

  7. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth;


    OBJECTIVE: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. METHODS: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial...... infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy. RESULTS: Patients randomized to losartan-based or atenolol...... decreased less during the first 2 years in patients randomized to losartan compared with atenolol (-0.13 +/- 0.24 vs. -0.19 +/- 0.25 mmol/l) and remained higher each year (1.38, 1.37, 1.42, 1.47, and 1.48 mmol/l vs. 1.32, 1.30, 1.36, 1.40, and 1.42 mmol/l, all P

  8. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats.

    Porvasnik, Stacy L; Germain, Sean; Embury, Jennifer; Gannon, Kimberley S; Jacques, Vincent; Murray, Justin; Byrne, Barry J; Shacham, Sharon; Al-Mousily, Faris


    Pulmonary arterial hypertension (PAH) is a life-threatening disease that results in right ventricular failure. 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. In the current study, the effects of PRX-08066 were assessed by using the monocrotaline (MCT)-induced PAH rat model. Male rats received 40 mg/kg MCT or phosphate-buffered saline and were treated orally twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks. Pulmonary and cardiac functions were evaluated by hemodynamics, heart weight, magnetic resonance imaging (MRI), pulmonary artery (PA) morphology, and histology. Cardiac MRI demonstrated that PRX-08066 (100 mg/kg) significantly (P PRX-08066 significantly reduced peak PA pressure at 50 and 100 mg/kg (P PRX-08066 therapy also significantly reduced right ventricle (RV)/body weight and RV/left ventricle + septum (P PRX-08066 (P PRX-08066 significantly attenuated the elevation in PA pressure and RV hypertrophy and maintained cardiac function. Pulmonary vascular remodeling was also diminished compared with MCT control rats. PRX-08066 prevents the severity of PAH in the MCT rat model.

  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

    Andrea Passantino


    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 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

    Ana P. Colossimo


    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.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

  10. 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

    Rosana dos Santos e Silva Martin


    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

  11. Hypertrophied hearts: what of sevoflurane cardioprotection?

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael


    cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia-reperfusion. METHODS: Anaesthetized juvenile...... in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia-reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem. RESULTS: The mean myocardial infarct size (% of area...

  12. Effects of astragaloside Ⅳ on electrocardiogram and action potential of ventricular myocytes in guinea pigs%黄芪甙Ⅳ对豚鼠心电图及心室肌动作电位的影响

    周云; 王俊杰; 赵伟; 张川; 张卫东


    Objective To observe the effects of astragaloside Ⅳ on electrocardiogram (ECG) and action potential of ventricular myocytes in guinea pigs. Methods ECG was recorded in vivo and ex vivo by using conventional ECG recording method from anesthetic guinea pigs and Langendoff perfusion model of hearts. Action potentials were recorded from isolated papillary muscles of right ventricles of guinea pigs by using microelectrode techniques. Results RR interval was prolonged by Astragaloside Ⅳ in a dose-dependent manner both in vivo and ex vivo. Astragaloside Ⅳ shortened action potential duration (APD), while had no effects on resting potential, action potential amplitude and maximal rate of depolarization. Conclusion Astragaloside Ⅳ exerts a negative chronotropic effect on heart and shortens APD of cardiac myocytes, which may be involved with calcium channels.%目的 观察黄芪甙Ⅳ对豚鼠心电图(ECG)及心室肌动作电位的影响.方法 分别在麻醉豚鼠和Langendoff心脏灌流模型上记录体表ECG和离体心脏ECG,采用细胞内微电极技术记录豚鼠右心室乳头肌的动作电位.结果 黄芪甙Ⅳ能延长豚鼠体表ECG和离体心脏ECG的RR间期,这一效应具有剂量依赖性.黄芪甙Ⅳ还能缩短动作电位的时程(APD),但对静息电位、动作电位幅度和最大去极速度没有明显影响.结论 黄芪甙Ⅳ具有负性变时作用,能缩短心肌细胞APD,其作用机制可能与慢钙通道有关.

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

    Olsen, M H; Christensen, M K; Wachtell, K


    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...

  14. Hipertrofia ventricular esquerda em pacientes com doença renal crônica em tratamento conservador Left ventricular hypertrophy in patients with chronic kidney disease under conservative treatment

    Rachel Bregman


    Full Text Available A doença cardiovascular (DCV permanece sendo uma das maiores causas de morte em pacientes com doença renal crônica (DRC. A hipertrofia ventricular esquerda (HVE está presente em 75% dos pacientes ao iniciarem diálise, sugerindo que esta deve estar presente precocemente no curso da DRC. Poucos estudos avaliaram a prevalência de HVE na pré-diálise. Foram avaliados 309 pacientes clinicamente estáveis em acompanhamento por pelo menos três meses em cinco Centros no Brasil. Perfil bioquímico e marcadores inflamatórios foram avaliados. Dados são apresentados como media ± DP. Observamos que a HVE esteve presente em 53% dos pacientes, idade = 60 ± 13 anos, e 55 ± 14 anos para aqueles sem HVE. Diabetes mellitus como doença de base esteve presente em 35% dos pacientes em ambos os grupos. Filtração glomerular estimada foi 30 ± 11 e 32 ± 12 mL/min para pacientes com HVE e sem, respectivamente (p = 0,19. A distribuição de pacientes mostrou que 60% com HVE se encontravam no estágio 4. Análise logística multivariada mostrou que eram determinantes independentes para HVE: idade (p Cardiovascular disease (CVD remains the major cause of death in patients with chronic kidney disease (CKD. Left ventricular hypertrophy (LVH is present in 75% of patients starting dialysis, suggesting that LVH might be present from an early stage of CKD. Few studies have addressed the predialysis prevalence of LVH. This study evaluated 309 clinically stable patients under treatment for at least three months at five Brazilian centers. Biochemical profile and inflammatory markers were assessed. Data were shown as mean ± SD. Left ventricular hypertrophy was present in 53% of the patients, whose mean age was 60 ± 13years. The mean age of those without LVH was 55 ± 14 years. Diabetes mellitus was the underlying disease in 35% of the patients in both groups. Estimated glomerular filtration rate was 30 ± 11 and 32 ± 12 mL/min for patients with and without LVH

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

    Wegscheider Karl


    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.

  16. Left ventricular hypertrophy index based on a combination of frontal and transverse planes in the ECG and VCG: Diagnostic utility of cardiac vectors

    Bonomini, Maria Paula; Juan Ingallina, Fernando; Barone, Valeria; Antonucci, Ricardo; Valentinuzzi, Max; Arini, Pedro David


    The changes that left ventricular hypertrophy (LVH) induces in depolarization and repolarization vectors are well known. We analyzed the performance of the electrocardiographic and vectorcardiographic transverse planes (TP in the ECG and XZ in the VCG) and frontal planes (FP in the ECG and XY in the VCG) to discriminate LVH patients from control subjects. In an age-balanced set of 58 patients, the directions and amplitudes of QRS-complexes and T-wave vectors were studied. The repolarization vector significantly decreased in modulus from controls to LVH in the transverse plane (TP: 0.45±0.17mV vs. 0.24±0.13mV, p<0.0005 XZ: 0.43±0.16mV vs. 0.26±0.11mV, p<0.005) while the depolarization vector significantly changed in angle in the electrocardiographic frontal plane (Controls vs. LVH, FP: 48.24±33.66° vs. 46.84±35.44°, p<0.005, XY: 20.28±35.20° vs. 19.35±12.31°, NS). Several LVH indexes were proposed combining such information in both ECG and VCG spaces. A subset of all those indexes with AUC values greater than 0.7 was further studied. This subset comprised four indexes, with three of them belonging to the ECG space. Two out of the four indexes presented the best ROC curves (AUC values: 0.78 and 0.75, respectively). One index belonged to the ECG space and the other one to the VCG space. Both indexes showed a sensitivity of 86% and a specificity of 70%. In conclusion, the proposed indexes can favorably complement LVH diagnosis

  17. Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy.

    Orosz, Andrea; Baczkó, István; Nagy, Viktória; Gavallér, Henriette; Csanády, Miklós; Forster, Tamás; Papp, Julius Gy; Varró, András; Lengyel, Csaba; Sepp, Róbert


    Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak-Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM.

  18. The association of left ventricular hypertrophy with metabolic syndrome is dependent on body mass index in hypertensive overweight or obese patients.

    Federico Guerra

    Full Text Available BACKGROUND: Overweight (Ow and obesity (Ob influence blood pressure (BP and left ventricular hypertrophy (LVH. It is unclear whether the presence of metabolic syndrome (MetS independently affects echocardiographic parameters in hypertension. METHODS: 380 Ow/Ob essential hypertensive patients (age ≤ 65 years presenting for referred BP control-related problems. MetS was defined according to NCEP III/ATP with AHA modifications and LVH as LVM/h(2.7 ≥ 49.2 g/m(2.7 in males and ≥ 46.7 g/m(2.7 in females. Treatment intensity score (TIS was used to control for BP treatment as previously reported. RESULTS: Hypertensive patients with MetS had significantly higher BMI, systolic and mean BP, interventricular septum and relative wall thickness and lower ejection fraction than those without MetS. LVM/h(2.7 was significantly higher in MetS patients (59.14 ± 14.97 vs. 55.33 ± 14.69 g/m(2.7; p = 0.022. Hypertensive patients with MetS had a 2.3-fold higher risk to have LVH/h(2.7 after adjustment for age, SBP and TIS (OR 2.34; 95%CI 1.40-3.92; p = 0.001, but MetS lost its independent relationship with LVH when BMI was included in the model. CONCLUSIONS: In Ow/Ob hypertensive patients MetS maintains its role of risk factor for LVH independently of age, SBP, and TIS, resulting in a useful predictor of target organ damage in clinical practice. However, MetS loses its independent relationship when BMI is taken into account, suggesting that the effects on MetS on LV parameters are mainly driven by the degree of adiposity.

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

    Bartram, P.; Hanel, B.; Gustafsson, F.; Mortensen, J.; Hesse, B. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark); Toft, J. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark)]|[Copenhagen City Heart Study, Epidemiological Research Unit (Denmark); Ali, S. [Dept. of Cardiology, Copenhagen University Hospital (Denmark)


    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 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.) With 1 fig., 26 tabs., 22 refs.

  1. Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction

    Emad Abro


    Full Text Available Altered operation of the renin-angiotensin-aldosterone system (RAAS and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS blockade in the spontaneously hypertensive rat (SHR, using co-treatment with an angiotensin II receptor blocker (ARB and an angiotensin-converting enzyme (ACE inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%, aggressive RAS blockade treatment with candesartan (3 mg/kg and perindopril (6 mg/kg does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2% significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit.

  2. Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

    Wang, W M; Liu, Z; Chen, G


    As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

  3. TGF-β1, released by myofibroblasts, differentially regulates transcription and function of sodium and potassium channels in adult rat ventricular myocytes.

    Kuljeet Kaur

    Full Text Available Cardiac injury promotes fibroblasts activation and differentiation into myofibroblasts, which are hypersecretory of multiple cytokines. It is unknown whether any of such cytokines are involved in the electrophysiological remodeling of adult cardiomyocytes. We cultured adult cardiomyocytes for 3 days in cardiac fibroblast conditioned medium (FCM from adult rats. In whole-cell voltage-clamp experiments, FCM-treated myocytes had 41% more peak inward sodium current (I(Na density at -40 mV than myocytes in control medium (p3 fold greater in FCM than control, which suggested that FCM effects could be mediated by TGF-β1. This was confirmed by pre-treatment with TGF-β1 neutralizing antibody, which abolished the FCM-induced changes in both I(Na and I(to. In current-clamp experiments TGF-β1 (10 ng/ml prolonged the action potential duration at 30, 50, and 90 repolarization (p<0.05; at 50 ng/ml it gave rise to early afterdepolarizations. In voltage-clamp experiments, TGF-β1 increased I(Na density in a dose-dependent manner without affecting voltage dependence of activation or inactivation. I(Na density was -36.25±2.8 pA/pF in control, -59.17±6.2 pA/pF at 0.1 ng/ml (p<0.01, and -58.22±6.6 pA/pF at 1 ng/ml (p<0.01. In sharp contrast, I(to density decreased from 22.2±1.2 pA/pF to 12.7±0.98 pA/pF (p<0.001 at 10 ng/ml. At 1 ng/ml TGF-β1 significantly increased SCN5A (Na(V1.5 (+73%; p<0.01, while reducing KCNIP2 (Kchip2; -77%; p<0.01 and KCND2 (K(V4.2; -50% p<0.05 mRNA levels. Further, the TGF-β1-induced increase in I(Na was mediated through activation of the PI3K-AKT pathway via phosphorylation of FOXO1 (a negative regulator of SCN5A. TGF-β1 released by myofibroblasts differentially regulates transcription and function of the main cardiac sodium channel and of the channel responsible for the transient outward current. The results provide new mechanistic insight into the electrical remodeling associated with myocardial injury.

  4. TGF-β1, Released by Myofibroblasts, Differentially Regulates Transcription and Function of Sodium and Potassium Channels in Adult Rat Ventricular Myocytes

    Kaur, Kuljeet; Zarzoso, Manuel; Ponce-Balbuena, Daniela; Guerrero-Serna, Guadalupe; Hou, Luqia; Musa, Hassan; Jalife, José


    Cardiac injury promotes fibroblasts activation and differentiation into myofibroblasts, which are hypersecretory of multiple cytokines. It is unknown whether any of such cytokines are involved in the electrophysiological remodeling of adult cardiomyocytes. We cultured adult cardiomyocytes for 3 days in cardiac fibroblast conditioned medium (FCM) from adult rats. In whole-cell voltage-clamp experiments, FCM-treated myocytes had 41% more peak inward sodium current (INa) density at −40 mV than myocytes in control medium (p3 fold greater in FCM than control, which suggested that FCM effects could be mediated by TGF-β1. This was confirmed by pre-treatment with TGF-β1 neutralizing antibody, which abolished the FCM-induced changes in both INa and Ito. In current-clamp experiments TGF-β1 (10 ng/ml) prolonged the action potential duration at 30, 50, and 90 repolarization (p<0.05); at 50 ng/ml it gave rise to early afterdepolarizations. In voltage-clamp experiments, TGF-β1 increased INa density in a dose-dependent manner without affecting voltage dependence of activation or inactivation. INa density was −36.25±2.8 pA/pF in control, −59.17±6.2 pA/pF at 0.1 ng/ml (p<0.01), and −58.22±6.6 pA/pF at 1 ng/ml (p<0.01). In sharp contrast, Ito density decreased from 22.2±1.2 pA/pF to 12.7±0.98 pA/pF (p<0.001) at 10 ng/ml. At 1 ng/ml TGF-β1 significantly increased SCN5A (NaV1.5) (+73%; p<0.01), while reducing KCNIP2 (Kchip2; −77%; p<0.01) and KCND2 (KV4.2; −50% p<0.05) mRNA levels. Further, the TGF-β1-induced increase in INa was mediated through activation of the PI3K-AKT pathway via phosphorylation of FOXO1 (a negative regulator of SCN5A). TGF-β1 released by myofibroblasts differentially regulates transcription and function of the main cardiac sodium channel and of the channel responsible for the transient outward current. The results provide new mechanistic insight into the electrical remodeling associated with myocardial injury. PMID:23393573

  5. Expression of TGF β1 in the Left Ventricular Tissue and its Relations to Left Ventricular Hypertrophy and Myocardial Interstitial Fibrosis in Renovasc ular Hypertensive Rats%转化生长因子β1在肾血管性高血压大鼠左心室的表达及与左室肥厚和心肌纤维化的关系探讨

    刘遂心; 孙明; 周宏研


    Objective To investigate the roles of T GFβ1 and TGFβ1 typeⅠrecepter(TβRⅠ) in development of myocardial hypert rophy and myo cardial interstitium remodelling in renovascular hypertensive rat.  Methods TGFβ1 and TβRⅠwere evaluated by qualitative and semi -qu antitative immunohistochemical staining to explore their distribution and ex peression in left ventricular tissue. Van Gieson staining were used in the stud y of total collagen in left ventricular interstitial tissue.  Results Compared with sham-operated rat(SOR),the expression of T GFβ1 andTβRⅠ in left ventricular tissue were significantly increased in RHR(P <0.01 all). In RHR the antibody to TGFβ1 reacted primarily with cytoplasma a nd myo cardial interstitium while antibody to TβRⅠreacted mainly with myocyte membran es with weak labeling in myocardial interstitium. In SOR,very mild labeling for TGFβ1 and TβRⅠin myocardiun was found with no labeli ng in myocardial interstitium. Correlative analysis revealed that TGFβ1 or T βRⅠ was positively correlated with left ventricular mass index(LVMI),negativel y correlated with grey level of myocardial total collagen. Conclusions TGFβ1 and TβRⅠmay play important roles in develo pment of left ventricular hypertrophy and myocardial interstitial fibrosis.%目的 探讨转化生长因子β1(TGFβ1)及TGFβ1Ⅰ型体受体(TβRⅠ)在高血压左室肥厚及 心肌纤维化方面的作用。方法 以二肾一夹肾血管性高血压大鼠(RHR)为模型,用免疫组化方法对TGFβ1及TGFβ1Ⅰ型受体(TβRⅠ)在左室心肌的分布及表达进行定性及半定量分析;用VG染色方法测定左室心肌总胶原浓度。结果 (1)RHR组左室重量指数(LVMI)明显高于对照组(SOR),心肌总胶原灰度值明显低于SOR组(\\%P\\%均<0.01);(2)TGFβ1及TβRⅠ在RHR组左室心肌中的表达较SOR组明显增强(\\%P\\%均<0.01)。TGFβ1表达主要位于心肌细胞浆和心肌间质,TβRⅠ主要位于心肌细胞

  6. Crocin, a carotenoid component of Crocus cativus, exerts inhibitory effects on L-type Ca(2+) current, Ca(2+) transient, and contractility in rat ventricular myocytes.

    Liu, Tao; Chu, Xi; Wang, Hua; Zhang, Xuan; Zhang, Yuanyuan; Guo, Hui; Liu, Zhenyi; Dong, Yongsheng; Liu, Hongying; Liu, Yang; Chu, Li; Zhang, Jianping


    Crocin, a carotenoid component of Crocus sativus L. belonging to the Iridaceae family, has demonstrated cardioprotective effects. To investigate the cellular mechanisms of these cardioprotective effects, here we studied the influence of crocin on L-type Ca(2+)current (I(Ca-L)), intracellular Ca(2+) ([Ca(2+)]i), and contraction of isolated rat cardiomyocytes by using the whole-cell patch-clamp technique and video-based edge detection and dual excitation fluorescence photomultiplier systems. Crocin inhibited I(Ca-L) in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) of 45 μmol/L and the maximal inhibitory effect of 72.195% ± 1.54%. Neither current-voltage relationship of I(Ca-L), reversal potential of I(Ca-L), nor the activation/inactivation of I(Ca-L) was significantly changed. Crocin at 1 μmol/L reduced cell shortening by 44.64% ± 2.12% and the peak value of the Ca(2+) transient by 23.66% ± 4.52%. Crocin significantly reduced amplitudes of myocyte shortening and [Ca(2+)]i with an increase in the time to reach 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of crocin may be attributed to the attenuation of [Ca(2+)]i through the inhibition of I(Ca-L) in rat cardiomyocytes and negative inotropic effects on myocardial contractility.

  7. Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

    Chronic hypobaric hypoxia (CHH) increases load on the right ventricle (RV) resulting in RV hypertrophy. We hypothesized that CHH elicits distinct responses, i.e., the hypertrophied RV, unlike the left ventricle (LV), displaying enhanced mitochondrial respiratory and contractile function. Wistar rats...

  8. 利多卡因对家兔左右心室外膜心肌细胞电不均一性的影响%Effects of Lidocaine on Cardiac Electrical Heterogeneity of Left and Right Subepicardial Myocytes in Ventricular Walls of Rabbits

    周军; 王腾; 胡河; 曹红; 秦牧


    Objective: To investigate the effects of lidocaine on action potential (AP) and sodium current (Ina) of left and right subepicardial myocytes in ventricular walls of rabbits. Methods: The sub-epicardial myocytes were obtained by enzymatic dissociation in left and right ventricular walls of rabbits. AP and Ina were recorded via whole-cell patch-clamp technique in control group and lidocaine group. Results: According to current clamp protocol, Aps which were recorded in subepicardial myocytes of both left and right ventricular walls were consisted of five phases from up-stroke to phase four, and attached to a dome in the second plateau of the Aps in control group, which was the typical characteristics of the Aps of subepicardial myocytes of ventricular wall. But lidocaine could delete the dome of the second plateau and degrade the amplitude of the Aps of subepicardial myocytes of left and right ventricular walls. It is special differences that Aps of the right subepicardial myocytes didn't have the second plateau and shaped an acute triangle. AP am-plitude(APA) was significantly cut down and APD50 and APD90 were shorted in subepicardial myocytes of left and right ventricular walls with administrating lidocaine (compared with control group, P<C0. 05). However, the APA and APD50 as well as APD90 in right subepicardial myocytes were more significantly attenuated when comparing with left subepicardial myocytes after treated by lidocaine (P<C0. 05 and 0.01, respectively). With the voltage clamp protocol, lidocaine significantly decreased the Ina under different command potential in subepicardial myocytes of left and right ventricular walls. And Ina in right subepicardial myocytes was blocked more seriously than that in left subepicardial myocytes with administrating lidocaine. Under -20 mV voltage clamp, Ina in left and right subepicardial myocytes were respectively decreased from (62. 1± 4. 5) and (54. 2±2. 9) to (40. 8 + 3. 2)and(26. 5±2.1) with lidocaine

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

    M.A. Carneiro-Júnior


    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 μm, 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 μm/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 μm/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.

  10. Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

    Peters, E L; Offringa, C; Kos, D; Van der Laarse, W J; Jaspers, R T


    A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

  11. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    胡琴; 李隆贵


    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  12. A Carbohydrate Fraction, AIP1, from Artemisia Iwayomogi Reduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K+ Channels in Rabbit Ventricular Myocytes

    Park, Won Sun; Son, Youn Kyoung; Ko, Eun A.; Choi, Seong Woo; Kim, Nari; Choi, Tae-Hoon; Youn, Hyun Joo; Jo, Su-Hyun; Hong, Da Hye; Han, Jin


    We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K+ current (IK) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC50 value of 56.1±5.5 µg/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating IK without significantly altering the resting membrane pote...

  13. 儿童左心室肥厚的临床病因分析%Etiological analysis of left ventricular hypertrophy in children

    李淑华; 黄萍; 张丽; 刘特长; 虢艳


    目的 了解儿童左心室肥厚(LVH)的病因分布.方法 对2005年3月至2008年3月在广州市儿童医院二维超声诊断LVH的27例患儿(男19例、女8例,年龄平均2.66岁)行病因诊断分析.结果 27例LVH中主动脉病变所致4例(14.8%),糖原累积病Ⅱ型所致2例(7.4%),肢端肥大症所致1例(3.7%),黏多糖蓄积症所致1例(3.7%);6例(22.2%)有家族史且无明显临床症状者考虑为肥厚型心肌病(HCM);病因未明占13例(48.1%),须进一步跟踪分析.结论 心脏影像学检查提示LVH的患儿病因复杂多样,不能简单根据影像学的结果诊断HCM,进一步完善LVH病因的诊断程序,区分儿童期及成人期LVH病因分布是必要的.%Objective Left ventricular hypertrophy (LVH), especially in children, is associated with a series of disorder including cardiac and systemic diseases. The etiological diagnosis should be evaluated in pediatric LVH patients. Methods From March 2005 to March 2008, clinical data from 27 patients (19 males and 8 females, mean age 2.66 years) with LVH diagnosed by two-dimensional ultrasound were analyzed. Results Among 27 patients, the prinary disease were aortic disease in 4 (14.8%) patients, glycogen-storage disease in 2 (7.4%) patients, acromegaly in one (3.7%) patient, and glycosaminoglycan disease in one (3.7%) patient. Six (22.2%) patients with positive family history of LVH were considered to have hypertrophic cardiomyopathy. The primary diseases were unclear in another 13 (48.1%) patients. Conclusions The primary diseases were complicated in LVH patients diagnosed by imaging examination. The diagnosis of LVH should be not only based on imping examination, but also relied on etiological diagnosis.

  14. Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats.

    Ashfaq Ahmad

    Full Text Available Hydrogen sulphide (H2S is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C and caffeine in drinking water (62mg/L for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE mRNA was quantified using real time polymerase chain reaction (qPCR.There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05 in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05 in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05 plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II and noradrenaline (NA but attenuates oxidative stress and improves pulse wave velocity which helps to suppress

  15. Relation of electrocardiographic left ventricular hypertrophy to blood pressure, body mass index, serum lipids and blood sugar levels in adult Nigerians.

    Opadijo, O G; Omotoso, A B O; Akande, A A


    Left ventricular hypertrophy (LVH) is considered an independent risk factor even in the absence of systemic hypertension. Electrocardiographic (ECG) LVH with repolarisation changes has been found in some countries to carry more coronary risk than LVH alone. How far this observation is true among adult Nigerians is not known. We therefore decided to study adult Nigerians with ECG-LVH with or without ST-T waves changes and compare them with normal age matched controls (without ECG-LVH) in relation with established modifiable risk factors such as systemic hypertension (BP), body mass index (BMI), fasting blood sugar (FBS) and serum lipids such as total cholesterol (Tc), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Adult Nigerians who were consecutively referred to the ECG laboratory were randomly recruited. Three hundred patients were studied. Their blood pressures (BP) as well as body mass indices were recorded after recording their resting 12 read ECG using portable Seward 9953 ECG machine. Their waist-hip ratio (WHR) was also recorded. Blood samples were taken to determine their fasting blood sugar and serum lipids. Their ECG tracings were read by the cardiologists involved in the study while the blood samples were analysed by the chemical pathologist also involved in the study. At the end of the ECG reading, the patients were divided into 3 groups according to whether there was no ECG-LVH (control group A), ECG-LVH alone (group B), and ECG-LVH with ST-T waves changes (group C). One hundred and fifty (50%) patients belonged to group A, 100 (33.3%) patients to group B and 50 (16.7%) group C. Group B patients were found to have higher modifiable risk factors in form of systemic BP. Tc, LDL-C, and WHR compared to group A. However, the group C patients had increased load of these coronary risk factors in terms of BP elevation, higher BMI, FBS, and scrum cholesterol compared to group B. In addition

  16. Simvastatin Modulates Remodeling of Kv4.3 Expression in Rat Hypertrophied Cardiomyocytes

    Feifei Su, Miaoqian Shi, Zhiqiang Yan, Dongbo Ou, Juntang Li, Zifan Lu, Qiangsun Zheng


    Full Text Available Objectives: Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.Methods: Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs underwent abdominal aortic banding (AAB for 7 weeks and angiotensin II (AngII treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial in the left ventricle was measured. The transient outward potassium current (Ito of NRVMs was recorded using a whole-cell patch-clamp method.Results: Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the Ito current and this effect was partially reversed by simvastatin.Conclusions: Simvastatin alleviated the reduction of Kv4.3 expression, Ito currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.

  17. Sarcoplasmic Reticulum Ca2+ Cycling Protein Phosphorylation in a Physiologic Ca2+ Milieu Unleashes a High-Power, Rhythmic Ca2+ Clock in Ventricular Myocytes: Relevance to Arrhythmias and Bio-Pacemaker Design

    Sirenko, Syevda; Maltsev, Victor A; Maltseva, Larissa A; Yang, Dongmei; Lukyanenko, Yevgeniya; Vinogradova, Tatiana; Jones, Larry; Lakatta, Edward G.


    Basal phosphorylation of sarcoplasmic reticulum (SR) Ca2+ proteins is high in sinoatrial nodal cells (SANC), which generate partially synchronized, spontaneous, rhythmic, diastolic local Ca2+ releases (LCRs), but low in ventricular myocytes (VM), which exhibit rare diastolic, stochastic SR-generated Ca2+ sparks. We tested the hypothesis that in a physiologic Ca2+ milieu, and independent of increased Ca2+ influx, an increase in basal phosphorylation of SR Ca2+ cycling proteins will convert stochastic Ca2+ sparks into periodic, high-power Ca2+ signals of the type that drives SANC normal automaticity. We measured phosphorylation of SR-associated proteins, phospholamban (PLB) and ryanodine receptors (RyR), and spontaneous local Ca2+ release characteristics (LCR) in permeabilized single, rabbit VM in physiologic [Ca2+], prior to and during inhibition of protein phosphatase (PP) and phosphodiesterase (PDE), or addition of exogenous cAMP, or in the presence of an antibody (2D12), that specifically inhibits binding of the PLB to SERCA-2. In the absence of the aforementioned perturbations, VM could only generate stochastic local Ca2+ releases of low power and low amplitude, as assessed by confocal Ca2+ imaging and spectral analysis. When the kinetics of Ca2+ pumping into the SR were increased by an increase in PLB phosphorylation (via PDE and PP inhibition or addition of cAMP) or by 2D12, self-organized, “clock-like” local Ca2+ releases, partially synchronized in space and time (Ca2+ wavelets), emerged, and the ensemble of these rhythmic local Ca2+ wavelets generated a periodic high-amplitude Ca2+ signal. Thus, a Ca2+ clock is not specific to pacemaker cells, but can also be unleashed in VM when SR Ca2+ cycling increases and spontaneous local Ca2+ release becomes partially synchronized. This unleashed Ca2+ clock that emerges in a physiological Ca2+ milieu in VM has two faces, however: it can provoke ventricular arrhythmias; or if harnessed, can be an important feature

  18. Effects of Hydrogen Sulfide on Electrophysiological Features of Rabbit Ventricular Myocytes%H2S对兔左心室心肌细胞电生理特性的影响

    陈立锋; 马淑红; 范凌; 赵兰平; 温晓竞; 马建伟; 张晓云; 王新满


    Objective:To investigate the effects of hydrogen sulfide(H2S)on action potentials(Ap)of rabbit left ventricular myocytes.Methods:By using standard intracellular microelectrode technique to record Ap,hydrogen sulfide was used to investigate the electrophysiological features of left ventricular myocytes.Electrophysiological parameters examined were:RP(resting potential),APA(amplitude of action potential),Vmax(maximal rate of depolarization),OS(over-shoot),APD20,APD50 and APD90(20%,50% and 90% of duration of action potential)and average rate of repolarization.Results:(1)Perfusion with NaHS(H2S donor,50μmol/L)led to a significant decrease in APD50(P<0.01),APD90(P<0.01)and a significant increase in average rate of repolarization(P<0.05).(2)Application of 100μmol/L NaHS resulted in a significant shortening in APD50(P<0.01),APD90(P<0.01)and a significant increase in average rate of repolarization(P<0.05).Compared with the result of 50μmol/L NaHS,100μmol/L NaHS led to a significant shortening in APD50(P<0.01),APD90(P<0.05)and a significant increase appeared in average rate of repolarization(P<0.05).(3)Application of 200μmol/L,400μmol/L and 1 000μmol/L NaHS led to a significant decrease in APA,RP and OS,a significant shortening in APD20,APD50 and APD90,a significant increase in average rate of repolarization in a concentration-depedent manner.Conclusion:H2S could significantly affect the electrophysiology of guinea pig ventricular myocytes in a concentration-depedent manner.%目的:探讨硫化氢(H2S)对兔左心室心肌细胞电生理特性的影响.方法:用标准微电极细胞内记录技术,观测硫化氢对兔左心室心肌细胞电生理特性的影响.观测指标:静息电位(resting potential,RP)、超射值(over-shoot,OS)、动作电位幅值(amplitude of action po-tential,APA)、0相最大除极速率(maximal rate of depolarization,Vmax)、复极20%、50%和90%时间(20%、50%and 90% of duration of action potential,APD20、APD50and APD90

  19. 白藜芦醇降低大鼠心室肌细胞内游离钙浓度%Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes

    刘政; 张利萍; 马会杰; 王川; 李明; 王庆山


    Resveratrol (trans-3,4',5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity.The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentratoin ([Ca2+]i) in rat ventricular myocytes. [Ca2+]i was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 μmol/L) reduced [Ca2+]i in normal and Ca2+-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca2+]i in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca2+ channel agonist Bay K8644 (10 μmol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca2+]i increase in Ca2+-free Tyrode's solution (P<0.01). When Ca2+ waves were produced by increasing extracellular Ca2+ concentration from 1 to 10 mmol/L,resveratrol (60 μmol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca2+]i. These results suggest that resveratrol may reduce the [Ca2+]i in isolated rat ventricular myocytes. The inhibition of voltagedependent Ca2+ channel and tyrosine kinase, and alleviation of Ca2+ release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease.%实验旨在研究白藜芦醇(resveratrol)对大鼠心室肌细胞内钙浓度(intracellular calcium concentratoin,[Ca2+]i)的影响.应用激光共聚焦显微镜技术记录心室肌细胞内的钙荧光强度.结果表明:在正常台氏液和

  20. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients

    Bang, Casper; Gerdts, Eva; Aurigemma, Gerard P;


    Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatatio...

  1. Effect of lacidipine on reveresing left ventricular hypertrophy (LVH) in hypertension patients%多普勒超声心动图评价拉西地平对高血压患者左室肥厚的逆转作用

    张新才; 谭学军; 孙玉红; 刘爱娟; 毛金英


    目的 探讨拉西地平对高血压患者左室肥厚(LVH)的逆转作用.方法 对53例高血压患者,在服用拉西地平治疗前,持续服药3个月后及持续服药6个月后,观察其对左室肥厚的逆转作用.结果 服用拉西地平治疗3个月及6个月后,患者血压显著下降,左室肥厚逆转.结论 服用拉西地平不仅能降低血压,长期服用还能逆转高血压引起的左室肥厚.%Objective To evaluate the effect of lacidipine on reveresing left ventricular hypertrophy (LVH) in hypertension patients. Methods The effect of lacidipine on reveresing left ventricular hypertrophy were measured in thirty-five patients with hypertension by doppler echocardiography before and after treatment with lacidipine for three months and six months. Results The blood pressure were decreased significantly and left ventricular hypertrophy was reversed after treatment with lacidipine for three months and six months. Conclusion Lacidipine not ony can decrease the high blood pressure, but also can reverse left ventricular hypertrophy caused by high blood pressure.

  2. 双苯氟嗪对豚鼠心室肌细胞L-钙电流的影响%Effect of dipfluzine on L-type calcium current in guinea pig ventricular myocytes

    张永健; 李德培; 薛保健; 王永利; 何瑞荣


    AIM: To study the effect of dipfluzine (Dip) on L-type calcium current in guinea pig ventricular myocytes.METHODS: Single myocytes were dissociated by enzymatic dissociation method.The current was recorded with the whole-cell configuration of the patch-clamp technique.RESULTS: Dip (0.3-30 μmo l/L)reduced the voltage-dependently activated peak value of ICa-L in a concentration-dependent manner. The characteristics of I-V relationship were not greatly altered by Dip, and the maximal activation voltage of Ica-L in the presence of Dip was not different from that of control.Steady-state activation of Ica-L was not affected markedly, and the half activation potential (V0.5) and the slope factor (κ) in the presence of Dip 3 μmol/L were not markedly different from those of the control. V0.5 value was (-12.8 ±1.7) mV in the control and (-13.2±2.4) mV in the presence of Dip 3 μ mol/L. The κ value was (7.1±0.4) mV in the control and (7.5±0.5) mV in the presence of Dip 3 μmol/L (n=7 cells from 3 hearts, P>0.05). Dip 3 μmol/L markedly shifted the steady-state inactivation curve of ICa-L to the left, and accelerated the voltage-dependent steady-state inactivation of calcium current.V0.5 value was (-19.7±2.4) mV in the control and (-31±6)mV in the presence of Dip 3 μmol/L.The κ value was (3.6±0.3) mV in the control and (1.8±0.2) mV in the presence of Dip 3 μmol/L (n=4cells from 2 hearts, P<0.05). Dip 3 μ mol/L markedly delayed half-recovery time of Ca2 + channel from inactivation from (40±11) to (288±63) ms (n=4, P<0.01).CONCLUSION: Dip mainly acts on the inac ti vated state of L-type calcium channel, accelerates the inactivation of calcium channel, and slows the recovery of calcium channel from inactivated state in guinea pig ventricular myocytes, through which the Ica-L is inhibited.%目的:观察双苯氟嗪(Dip)对豚鼠心室肌细胞L-型钙电流(ICa-L)的影响.方法:酶解法制备单个心室肌细胞.应用全细胞膜片箝技术记录

  3. Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy

    Xiao-dong WU; De-zai DAI; Qiu-pin ZHANG; Feng GAO


    AIM: To study the alteration in the mRNA level of cardiac ryanodine receptor 2 (RyR2) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in L-thyroxin-induced hypertrophy. METHODS: L-thyroxin (500 g/kg) daily was injected for 10 d. RT-PCR was used to determine mRNA expression. RESULTS: An increase in the relative amount of RyR2 (111%) and SERCA mRNA (65 %) expression was observed in the hypertrophied rats (RyR2:77± 11; SERCA: 87± 10, n=9) compared with the normal rats (RyR2: 36± 10; SERCA: 53± 10, n=9). Propranolol was effective to inhibit the increase in RyR2 (51±7) and SERCA (63±13) mRNA expression in hypertrophied rats,respectively. Verapamil also reduced RyR2 (62±5) and SERCA (75±8) mRNA expression. CONCLUSION: Both RyR2 and SERCA mRNA level in L-thyroxin-induced cardiac hypertrophy was over-expressed and propranolol or verapamil inhibited the alteration.

  4. 原发性高血压左室肥厚与血压变异性的关系%The Relationship between Left Ventricular Hypertrophy and the Progress of Blood Pressure Variability

    张虹; 彭璐; 冯莉; 赵兴山


    目的:探讨原发性高血压(EH)患者左室肥厚(LVH)与血压变异性(BPV)的关系.方法:143例EH患者根据超声心动图测定的左室重量指数(LVMI)分为LVH组及不伴LVH(单纯高血压)组,运用24h动态血压(ABPM)监测技术,与正常对照组分别计算BPV.比较各组之间的差异,并分析BPV与LVMI之间的关系.结果:与对照组相比,LVH组及不伴LVH组均显示BPV明显升高,LVH组BPV较不伴LVH组明显升高.结论:EH患者体内自主神经功能失衡,交感与副交感神经的双重损害参与了高血压的左室重构机制,可能伴随左室重构过程.BPV是评价心血管自主神经活动的无创指标,与高血压靶器官损害关系密切.%Objective:To investigated the clinical significance of blood pressure variability (BPV)in essential hypertension with left ventricular hypertrophy(LVH).Methods:143 essential hypertensive patients and 46 control persons received examinations by 24-hour ABPM.The patients were divided into 2 groups by the result of LVMI.BPV parameters were observed.Results:BPV in hypertension group with or without left ventricular hypertrophy was significantly higher than control group.And BPV in hypertension was significantly higher than control group.Conclusion:There was autonomic nerve imbalance in essential hypertension.The impairment of sympathetic and parasympathetic function might be involved in pathogenesis of left ventricular remodeling .The degree of impairment seemed to be ongoing severe in the modeling peocess of left ventricular structure.BPV has been regarded as an independent index reflecting autonomic nervous system in cardiovascular regulation,BPV has a close relationship with target organ damage of hypertension.

  5. FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.

    Okamoto, Ryuji; Li, Yuxin; Noma, Kensuke; Hiroi, Yukio; Liu, Ping-Yen; Taniguchi, Masaya; Ito, Masaaki; Liao, James K


    The Rho-associated coiled-coil containing kinases, ROCK1 and ROCK2, are important regulators of cell shape, migration, and proliferation through effects on the actin cytoskeleton. However, it is not known whether ROCK2 plays an important role in the development of cardiac hypertrophy. To determine whether the loss of ROCK2 could prevent cardiac hypertrophy, cardiomyocyte-specific ROCK2-null (c-ROCK2(-/-)) were generated using conditional ROCK2(flox/flox) mice and α-myosin heavy-chain promoter-driven Cre recombinase transgenic mice. Cardiac hypertrophy was induced by Ang II infusion (400 ng/kg/min, 28 d) or transverse aortic constriction (TAC). Under basal conditions, hemodynamic parameters, cardiac anatomy, and function of c-ROCK2(-/-) mice were comparable to wild-type (WT) mice. However, following Ang II infusion or TAC, c-ROCK2(-/-) mice exhibited a substantially smaller increase in heart-to-body weight ratio, left ventricular mass, myocyte cross-sectional area, hypertrophy-related fetal gene expression, intraventricular fibrosis, cardiac apoptosis, and oxidative stress compared to control mice. Deletion of ROCK2 in cardiomyocytes leads to increased expression of four-and-a-half LIM-only protein-2 (FHL2) and FHL2-mediated inhibition of serum response factor (SRF) and extracellular signal-regulated mitogen-activated protein kinase (ERK). Knockdown of FHL2 expression in ROCK2-deficient cardiomyocytes or placing ROCK2-haploinsufficient (ROCK2(+/-)) mice on FHL2(+/-)-haploinsufficient background restored the hypertrophic response to Ang II. These results indicate that cardiomyocyte ROCK2 is essential for the development of cardiac hypertrophy and that up-regulation of FHL2 may contribute to the antihypertrophic phenotype that is observed in cardiac-specific ROCK2-deficient mice.

  6. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C


    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  7. Correlation of right ventricular hypertrophy and vitamin D, atrial fibrillation and NT-proBNP in patients with pulmonary heart disease%肺心病患者右室肥厚与维生素D、房颤及NT-proBNP的关系

    陈荣花; 张瑞荣; 王希柱; 宋巧凤; 刘婷婷; 朱艳辉


    Objective To investigate correlation of right ventricular hypertrophy and vitamin D , atrial fibrillation and NT-proBNP in patients with pulmonary heart disease.Methods 40 cases of pulmonary heart disease were selected, according to whether the right ventricular hypertrophy or not, and divided into hypertrophy group and non hypertrophy group.Echocardiography, serum 25 hydroxy vitamin D, 24 h dynamic electrocardiogram and NT-proBNP level were detected, and the correlation were detected between the right ventricular hypertrophy and influence factors.ResuIts The right ventricular anterior wall ( RVAW) and right ventricular diastolic diameter ( RVDd) in hypertrophy group were significantly greater than those in non hypertrophy group (P<0.05).The serum 25 hydroxy vitamin D levels in hypertrophy group was lower than that in non hypertrophy group (P<0.05), but there was no significant correlation of right ventricular hypertrophy and 25 hydroxy vitamin D levels(r=-0.189,P=0.424).The thickness of right ventricular anterior wall in atrial fibrillation group was greater than that in non atrial fibrillation group (P<0.05), but there was no significant correlation of right ventricular hypertrophy and atrial fibrillation times(r=0.178,P=0.452).Serum NT-proBNP levels in hypertrophy group was higher than that in non hypertrophy group (P<0.05), but there was no significant correlation of right ventricular hypertrophy and serum NT-proBNP levels(r=-0.105, P=0.660).ConcIusion Patients with right ventricular hypertrophy of pulmonary heart disease who has a lower serum 25 hydroxy vitamin D level and a higher NT-proBNP level.Patients with atrial fibrillation has a thicker RVAW.However, there was no correlation of above influence factors.%目的:探讨肺心病患者右室肥厚与维生素D、房颤及NT-proBNP的关系。方法选取河北唐山市人民医院收治的肺心病患者40例,根据是否伴有右室肥厚分为肥厚组以及非肥厚组。对2组患者进行

  8. High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.

    Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J; Presson, Robert G; Petrache, Irina; Kline, Jeffrey; Lahm, Tim


    Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.

  9. Changes in ECG features and clinical prognosis of ventricular electrical storm in patients with left ventricular hypertrophy and acute myocardial infarction%左心室肥厚并急性心肌梗死室性电风暴心电图对预后的影响

    于文江; 王为民


    目的 探讨沿海居民高血压性左室肥厚(left ventricular hypertrophy,LNH)并急性心肌梗死(acute myocardial infarction,AMI)后心电图特征性改变,评估室性电风暴与临床预后危险分层.方法 选择急诊住院有高皿压性LVH并AMI室性电风暴(室速或室颤)317例(Ⅱ组),另选无高血压性LVH室性电风暴AMI 109例(Ⅰ组)进行心电图检查和持续心电监护,分析心电图特征与临床高危特点.结果 室性电风暴组以高血压LVH并AMI患者心电图指标心房终末电势异常、∑ST段抬高振幅、ST段抬高导联数、QTc间期延长、对应导联ST段振幅下移等特征,梗死部位以前壁或复合前壁,并以左前降支合并回旋支或/和右冠脉完全闭塞多支病变为主,与Ⅰ组比较差异有统计学意义(P<0.05或P<0.01),临床并发泵衰竭、AMI扩展、住院病死率、室性电风暴AMI发病后6 h内发生率明显增多(P<0.01).结论 高血压性LVH并AMI室性电风暴患者,心电图多项指标异常对临床预后有预测作用.%Objective To investigate changes in ECG feature and clinical prognosis of ventricular electrical storm (VES) in patients with left ventricular hypertrophy (LVH) and acute myocardial infarction (AMI). Methods Three hundred and seventeen cases of left ventricular hypertrophy induced by hypertension and combined with AMI (Group Ⅱ) from emergency inpatients, and another 109 patients without LVH induced by hypertension and accompanied with AMI (Group Ⅰ) were chosen to have sustained ECG monitoring, analyze ECG features and clinical high risks. Results Clinical features, such as abnormality in PTFvl,ΣST segment elevation amplitude, ST segment elevation leads, ST segment reduction amplitude leads, QTc interval prolongation could be noted in the VES group. Infarction could be seen at sites of anterior and complex anterior walls, and dominant clinical signs were mainly at left descending branches accompanied by circumflex arteries and

  10. Heart Hypertrophy Caused by Obesity and Physical Exercises

    Zazycki, Sabrina Pereira; Universidade Estadual de Maringá; Gomes, Célia Regina de Godoy; Universidade Estadual de Maringá


    The heart is mainly composed of myocytes, blood vessels and collagen interstitial matrix. When these factors are in equilibrium they contribute towards the maintenance of the heart’s form and function. Heart growth after birth mainly occurs through hypertrophy of the cardiomyocyte and the proliferation of interstitial components. This occurs because cardiomyocytes lose their ability to perform complete mitosis resulting in the absence of cell hyperplasia. Cardiomyocyte hypertrophy, the most e...

  11. Sympathetic nerve in rat with pressure overload left ventricular hypertrophy%瑞舒伐他汀对压力超负荷肥厚大鼠心脏结构和交感神经重构的影响

    廖颖; 曲秀芬; 刘丽; 董兴模; 尹德春


    Objective To explore the remodeling mechanism of myocardium and sympathetic nerve in pressure overload left ventricular hypertrophy and elucidate the protective effect of statins. Methods Pressure-overload left ventricular hypertrophy (LVH) of rats was induced by partial coarctation of abdominal aorta; a sham-operated group served as the control (SHAM, n=22). At 8 weeks pest-operation, the animals were divided into two groups and a 12-week treatment period was investigated. At the end of treatment period, eehocardiographic evaluations and hemodynamic measurements were performed. Sympathetic innervation was investigated by analyzing nerve growth factor (NGF), growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Results In LVH rats, a significant increase of left ventricular weight, left ventricular weight/body weight, echocardiographic left ventricular end-diastolic diameter, interventricular septum thickness, posterior left ventricular wall thickness, left ventricular systolic pressure and dP/dt was observed. The expressions of NGF and GAP43 protein were significantly down-regulated (0.82±0.06 vs 1.53±0.10, 0.68±0.06 vs 0.81±0.10) and TH level was up-regulated (0.44±0.10 vs 0.62±0.06) by RSV treatment. Conclusion A HMG CoA inhibitor reverses the development of left ventrieular hypertrophy and inhibits sympathetic innervation in abdominal aortic-clamped animals.%目的 探讨大鼠肥厚心肌结构重构、交感神经重构机制及他汀药物的保护作用.方法 62只雄性Wistar大鼠行腹主动脉缩窄术,8周造成压力超负荷性心肌肥厚模型,分为肥厚组和瑞舒伐他汀组,另设22只作为假手术组.瑞舒伐他汀组灌胃给药(10 mg·kg-1·d-1)连续12周后进行超声心动图和血流动力学指标测定.免疫组化法测定心肌中酪氨酸羟化酶(TH)和生长相关因子43(GAP43),Western印迹法检测心肌的TH、GAP43和神经生长因子(NGF)表达水平.结果 (1)肥厚组左室重量(LVW)、左室

  12. Evaluation of Left Ventricular Function in Patients with Apex-hypertrophy Using Speckle Tracking Imaging%斑点追踪显像对心尖肥厚型心肌病左室功能的评价分析

    王春梅; 唐琪; 穆玉明; 李艳红


    Objective To evaluate the left ventricular function in patients with apex - hypertrophy using speckle tracking imaging.Methods A total of 18 patinents with apex - hypertrophy ( HCM ) and 20 normal controls were enrolled in this study.Images of apacial 4-chamber, 2 - chamber and ventricular short - axises ( anular, papillary - muscle, apex ) were obtained ; the peak - systolic longitudinal strain ( SL ), circumfrencial strain ( SC ) and radial strain ( SR ) of all segments were analyzed.Results SL, SC, and SR of all segments in the HCM group were lower than those in normal controls ( P <0.05 ).Compared with normal controls, SL was lower in all segments in HCM group.SR was lower in most segments in the angular and the papillary - muscle views; SC was lower in several segments in the angular and the papillary - muscle views.Conclusion The longitudinal and radial systolic function among HCM patients is decreased, especially for the longitudinal systolic function.Changes of regional SL, SR and SC are promising indices that reflect these changes.%目的 探讨斑点追踪显像评价心尖肥厚型心肌病左室收缩功能的改变.方法 记录18例心尖肥厚型心肌病患者(HCM组)和20例健康对照者(对照组),获取二维灰阶图像,分析各个心肌节段收缩期峰值的纵向应变(SL)、径向应变(SR)和周向应变(SC).结果 HCM组心肌整体SL、SR及SC收缩期峰值应变均明显低于对照组(P<0.05).HCM组所有节段的收缩期峰值SL均明显低于对照组;与对照组相比,左房室瓣及乳头肌水平大多数节段的SR降低,左房室瓣及乳头肌水平个别节段的SC降低,心尖水平所有节段的SC及SR均明显降低(P<0.05).结论 HCM患者左室长轴和短轴收缩功能均降低,以长轴功能减弱明显,局部心肌SL、SR及SC的变化可反映心肌的功能改变.

  13. Two-dimensional strain analysis of the global and regional myocardial function for the differentiation of pathologic and physiologic left ventricular hypertrophy: a study in athletes and in patients with hypertrophic cardiomyopathy.

    Butz, T; van Buuren, F; Mellwig, K P; Langer, C; Plehn, G; Meissner, A; Trappe, H J; Horstkotte, D; Faber, L


    Two-dimensional strain (2DS) is a novel method to measure strain from standard two-dimensional echocardiographic images by speckle tracking, which is less angle dependent and more reproducible than conventional Doppler-derived strain. The objective of our study was to characterize global and regional function abnormalities using 2DS and strain rate analysis in patients (pts) with pathological left ventricular hypertrophy (LVH) caused by non-obstructive hypertrophic cardiomyopathy (HCM), in top level athletes, and in healthy controls. The hypothetical question was, if 2DS might be useful as additional tool in differentiating between pathologic and physiologic hypertrophy in top-level athletes. We consecutively studied 53 subjects, 15 pts with hypertrophic cardiomyopathy (HCM), 20 competitive top-level athletes, and a control group of 18 sedentary normal subjects by standard echocardiography according to ASE guidelines. Global longitudinal strain (GLS) and regional peak systolic strain (PSS) was assessed by 2DS in the apical four-chamber-view using a dedicated software. All components of strain were significantly reduced in pts with HCM (GLS: -8.1 ± 3.8%; P < 0.001) when compared with athletes (-15.2 ± 3.6%) and control subjects (-16.0 ± 2.8%). In general, there was no significant difference between the strain values of the athletes and the control group, but in some of the segments, the strain values of the control group were significantly higher than those in the athletes. A cut-off value of GLS less than -10% for the diagnosis of pathologic hypertrophy (HCM) resulted in a sensitivity of 80.0% and a specificity of 95.0%. The combination of TDI (averaged S', E') and 2DS (GLS) cut-off values for the detection of pathologic LVH in HCM demonstrated a sensitivity of 100%, and a specificity of 95%. Two-dimensional strain is a new simple and rapid method to measure GLS and PSS as components of systolic strain. This technique could offer a unique approach to quantify

  14. Effects of Zhenwu decoction on rats with pressure-overloaded left ventricular myocardial hypertrophy XIE%真武汤冲剂对压力负荷性心肌肥厚的影响

    谢志翔; 王舒茵; 梁子敬; 曾量波


    Objective To investigate the effects of Zhenwu decoction (a herbal preparation made in a form of instant granules readily soluble into decoction to administer) on rats with chronic pressure-overloaded left ven-tricular hypertrophy. Method All the male SD rats were randomly(random number) divided into 3 groups: sham operation group (n= 8), operation group (n= 15) and herbal medicine group (n= 15). The model of myocar-dial hypertrophy was made by gradually constricting the abdominal aorta. After 16 weeks, cardiac ultrasonography was used in rats of all groups to ascertain the post-operational left ventricular (LV) hypertrophy established. And the Zhenwu decoction was added in the herbal medicine group in a dose of 12 g/kg mixed in feedstuff fed for 8 weeks. After 24 weeks, the weight and structure as well as function of the heart of rats in each group were mea-sured by high-frequency ultrasonography, and Massion stain was performed on cardiac muscles. Meanwhile, both the total collagen volume fraction (CVF-T) and non-coronary vessel collagen volume fraction (CVF-NV) were ana-lyzed. Results There was an increase in the weight of the heart with a predominance of the left ventricle in the operation group (P < 0.05) . The heart was enlarged with diastolic interventricular septum thickness (IVSt) and left ventricular posterior wall thickness (LVPWt) increased predominantly (P < 0.01). There was a significant decrease in cardiac function (P < 0.05). In herbal medicine group, both the weight and volume of heart were lower than those in operation group with predominance of IVSt and systolic left ventricular wall (P < 0.01 both).And the cardiac function of rats in herbal group was better (P < 0.05). Interstitial and collagen hyperplasia increased significantly in the rats of operation group found by pathological analysis. In herbal medicine group, the pathological changes were blunted in varied magnitude with significant decrease in CVF-T and CVF-NV in compari

  15. Signaling Pathways Involved in Cardiac Hypertrophy

    Tao Zewei; Li Longgui


    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  16. Relation of maximum blood pressure during exercise and regular physical activity in normotensive men with left ventricular mass and hypertrophy. MARATHOM Investigators. Medida de la Actividad fisica y su Relación Ambiental con Todos los Lípidos en el HOMbre.

    Molina, L; Elosua, R; Marrugat, J; Pons, S


    The relation between maximum systolic blood pressure (BP) during exercise and left ventricular (LV) mass is controversial. Physical activity also induces LV mass increase. The objective was to assess the relation between BP response to exercise and LV mass in normotensive men, taking into account physical activity practice. A cross-sectional study was performed. Three hundred eighteen healthy normotensive men, aged between 20 and 60 years, participated in this study. The Minnesota questionnaire was used to assess physical activity practice. An echocardiogram and a maximum exercise test were performed. LV mass was calculated and indexed to body surface area. LV hypertrophy was defined as a ventricular mass index > or =134 g/m2. BP was measured at the moment of maximum effort. Hypertensive response was considered when BP was > or =210 mm Hg. In the multiple linear regression model, maximum systolic BP was associated with LV mass index and correlation coefficient was 0.27 (SE 0.07). Physical activity practice and age were also associated with LV mass. An association between hypertensive response to exercise and LV hypertrophy was observed (odds ratio 3.16). Thus, BP response to exercise is associated with LV mass and men with systolic BP response > or =210 mm Hg present a 3-times higher risk of LV hypertrophy than those not reaching this limit. Physical activity practice is related to LV mass, but not to LV hypertrophy.

  17. Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

    Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo


    Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β.

  18. Recording of Single Channel Ca2+ Current and the Characterization of Its Electrophysiological Characteristics in Rat Ventricular Myocytes%大鼠心室肌细胞单通道钙电流的记录及其电生理学特性分析

    刘书源; 刘雅茹; 高青华; 赵美眯; 赵金生; 孙雪菲; 郝丽英


    Objective To isolate rat ventricular myocytes, record single channel Ca2+ current and analyze its electrophysiological characteristics. Methods Rat ventricular myocytes were isolated with collagenase-digestion method; L-type calcium channel currents were recorded with the cell-attached and inside-out configurations of patch clamp technology, and analyzed with pClamp10 software. Results The survived rat ventricular myocytes separated in current study were rod-shaped or cylindrical with clear stripes. The currents of L-type calcium channel were recorded and analyzed:the average current amplitude was (1.13 ± 0.01 )pA,conductance was 19 pS,the average open time constant was (1.35 ± 0.03)ms,and the average closing time constant was (46.75 ± 10.04)ms. In addition, the run-down phenomenon of the L-type calcium channel was observed in the inside-out mode. Conclusion The separated rat ventricular myocytes were suitable for single channel recording of patch clamp technique; the basic characteristics of L-type Ca2+ channel were consistent with the literature.%目的 分离大鼠心室肌细胞,记录大鼠心室肌细胞的单通道钙电流,并分析其基本电生理学性质.方法 胶原酶法分离大鼠心室肌细胞;应用膜片钳技术细胞贴附式和内膜向外式记录L-型钙通道的电流,并用pClamp 10分析软件进行分析.结果分离得到大鼠心室肌细胞,细胞存活形态良好,呈杆状或柱状,具有清晰的横纹.记录到的L-型钙通道单通道电流,平均电流幅度为(1.13±0.01)pA,电导为19 pS,平均开放时间常数为(1.35±0.03)ms,平均关闭时间常数为(46.75±10.04) ms.此外,还记录到L-型钙通道的Run-down现象.结论 本实验分离得到的大鼠心室肌细胞适用于膜片钳单通道记录模式;记录到的L-型钙通道的基本电生理学性质与文献报道相符.

  19. Captopril Combined urban Tampa Bay Sand Treatment of High Blood Pressure and Improve Left Ventricular Myocardial Hypertrophy Curative Effect Observation%卡托普利联合厄贝沙坦治疗高血压及改善左室心肌肥厚疗效观察

    王泽; 杜莉


      目的:观察卡托普利联合厄贝沙坦治疗高血压及改善左室心肌肥厚疗效.方法:选择高血压患者并行心脏彩超(提示左室心肌肥厚)患者118例,给予卡托普利联合厄贝沙坦口服治疗半年,检查血压及心脏彩超,了解左室舒张末期内径(LVDd)、舒张末期室间隔厚度(IVSd)、左室后壁厚度(LVPWd)、及计算左室重量指数(LVMI)评价疗效.结果:高血压患者治疗后收缩压及舒张压明显降低,左室舒张末期内径、舒张末期室间隔厚度、左室后壁厚度、及计算左室重量指数明显改善.治疗前后对比存在统计学意义(P<0.05).结论:卡托普利联合厄贝沙坦治疗高血压有效并明显改善左室心肌肥厚.%  Objective:To observe the captopril combined urban Tampa bay sand treatment of high blood pressure and improve left ventricular myocardial hypertrophy curative effect.Methods: choose hypertension and heart do colour to exceed (hint left ventricular myocardial hypertrophy) patient 118 examples, give captopril combined e bay sand jotham oral treatment half a year, check blood pressure and heart to exceed, understand left ventricular end-diastolic diameter (LVDd), end-diastolic interventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), and calculation left ventricular mass index (LVMI) assessment of curative effect. Results:After treatment in patients with high blood pressure and diastolic pressure systolic blood pressure significantly, left ventricular end-diastolic diameter, end-diastolic interventricular septum thickness, left ventricular posterior wall thickness, and calculation left ventricular weight index obviously improved. Existing contrast before and after treatment (P < 0.05). Conclusions:captopril combined e bay sand jotham could treat high blood pressure effectively and significantly improve left ventricular myocardial hypertrophy.

  20. Extracellular matrix remodelling in myocardial hypertrophy and failure : focus on osteopontin.

    Francia, Pietro; Uccellini, Arianna; Frattari, Alessandra; Modestino, Anna; Ricotta, Agnese; Balla, Cristina; Scialla, Ludovica; Volpe, Massimo


    Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.

  1. Mid-ventricular hypertrophy complicated with the lengthy of mitral valve leaflets lead to dynamic left ventricular outflow tract obstruction: A case report and literature review%左心室中部肥厚合并二尖瓣冗长致左室流出道梗阻——病例报告与文献复习

    洪李锋; 罗松辉; 夏璐; 范莹; 胡良焱; 项金洲


    Objective:To investigate the etiology,manifestations and the progress regarding the diagnosis and treatment for left ventricular outflow tract obstruction.Methods:Diagnosis and treatment of one case with mid-ventricular hypertrophy complicated with the lengthy of mitral valve leaflets lead to dynamic left ventricnlar outflow tract obstruction was followed up and reviewed with related literatures.Resuhs:The etiology of ventricular outflow tract obstruction was complex and the incidence was rather high.Transthoracic two-dimensional exercise echocardiography with transesophageal echocardiography analysis is the most effective non-invasive screening and prognostic predictive tool for left ventricular outflow tract obstruction.Conclusions:It is mandatory to selectively conduct multiple imaging examinations which mainly include exercise echocardiography and selectively left ventriculography in order to successfully improve the diagnosis of left ventricular outflow tract obstruction.%目的:探讨左室流出道梗阻的病因分类、临床表现和诊治进展.方法:对1例左心室中部肥厚合并二尖瓣前叶冗长致隐匿性左室流出道梗阻患者的诊治过程进行全程追踪随访,结合复习相关文献.结果:左室流出道梗阻病因复杂,发生率较高;超声心动图运动试验结合经食道超声探查是左室流出道梗阻最有效的无创筛查和随访评价手段,必要时左心室造影和测压可进一步明确诊断.结论:对左心室肥厚患者常规开展运动超声心动图、必要时左心室造影等多种影像学检查可以有效提高左室流出道梗阻及其病因的诊断正确率.

  2. Study on tissue Doppler imaging in diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease%组织多普勒成像技术诊断矽肺肺心病患者右心室肥大的研究



    Objective To investigate the value of tissue Doppler imaging (TDI) in the diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease.Methods A total of 50 cases of silicosis complicated by chronic pulmonary heart disease in our hospital underwent conventional electrocardiography (ECG) and TDI.The detection rates for right ventricular hypertrophy by two methods were compared.Results Of 50 cases of silicosis complicated by chronic pulmonary heart disease,19 were diagnosed with right ventricular hypertrophy by ECG,with a detection rate of 38.0%; 29 were diagnosed with right ventricular hypertrophy by TDI,with a detection rate off 58.0%.Statistical analysis suggested that TDI leads to a significantly higher detection rate for right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease (x2=4.006,P=0.036).Conclusion Both TDI and ECG can be used for detecting right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease,but the detection rate is higher when TDI is employed.In addition,ECG cannot directly reflect the increase in pulmonary artery pressure.Therefore,TDI is more suitable for the diagnosis of right ventricular hypertrophy in patients with silicosis complicated by chronic pulmonary heart disease and provides a strong diagnostic basis for the clinical treatment of silicosis complicated by pulmonary heart disease.%目的 探讨组织多普勒成像在矽肺并发慢性肺源性心脏病患者右心室肥大的诊断价值.方法 将本院50例矽肺并发慢性肺源性心脏病患者,分别行常规心电图和组织多普勒成像检查,比较两种方法右心室肥大检出率.结果 入组的50例矽肺并发慢性肺源性心脏病患者经心电图检查,发现右心室肥大患者19例,检出率为38.0%,而组织多普勒成像技术检查发现右心室肥大患者29例,检出率为58.0%,组织多

  3. Value of 4D-strain imaging echocardiography in detecting left ventricular systolic dysfunction in patients with aortic stenosis

    ZHENG Zhi-chao; LI He-zhi; LI Chang-mao; CHEN Ou-di; FEI Hong-wen; LIN Qiong-wen


    Background The myocyte dysfunction may be present in aortic stenosis (AS) patients with preserved left ventricular ejection fraction (LVEF).Early aortic valve replacement (AVR) can reverse the LV hypertrophy and improve LV systolic performance and clinical outcome.Strain imaging has demonstrated to be the most appropriate method to evaluate LV myocardial contractility.However,4D-strain imaging echocardiography for the detection of subclinical left ventricular dysfunction in AS patients with preserved LVEF is seldom studied.Methods We prospectively enrolled 30 consecutive moderate to severe AS patients with preserved LVEF,and 30 healthy controls.Conventional echocardiography and 4D-strain imaging echocardiography were undergone in two groups.The 4D strain echocardiographic analyses were undertaken by using 4D Auto LVQ software.Results Compared with the healthy controls,the moderate to severe AS patients with preserved LVEF had significantly decreased global radial strain (GRS),global longitudinal strain (GLS),global area strain (GAS) and 4D strain (P < 0.05),had significantly increased left ventricular end-diastolic volume index (LVEDVI) and left ventricular mass index (LVMI) (P < 0.05),and had lower global circumferential strain (GCS) (P > 0.05).Conclusions Impaired LV myocardial contractility exists in moderate to severe AS patients,although LVEF is preserved.4D-strain imaging echocardiography can detect early left ventricular dysfunction in AS patients with preserved LVEF.

  4. 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

    Francisco de Assis Costa


    electrocardiográficos, correlacionándolos al índice de masa del ventrículo izquierdo (IMVI que se obtuvo mediante el ecocardiograma. MÉTODOS: Estudio transversal que incluyó a 100 pacientes (58 varones y 42 mujeres, edad de 46,2 ± 14,0 años con ERC de todas las etiologías, desde hace al menos 6 meses en hemodiálisis (HD. Se obtuvieron electrocardiograma (ECG y ecocardiograma de los pacientes, siempre hasta una hora tras el término de las sesiones de HD. RESULTADOS: La HVI se detectó en 83 pacientes (83%, de los que 56 (67,4% presentaban el estándar concéntrico y 27 (32,6% el estándar excéntrico de HVI. Todos los métodos electrocardiográficos estudiados tuvieron sensibilidad, especificidad y exactitud diagnósticas superiores al 50%. Mediante la correlación lineal de Pearson con el IMVI, solamente el criterio de Sokolow-Lyon voltaje no presentó coeficiente > 0,50. Sin embargo, el cálculo de la razón de verosimilitud evidenció que el ECG tiene poder discriminatorio para diagnóstico de HVI en la población estudiada, con énfasis para los criterios de Producto de Cornell y Romhilt-Estes. No hubo correlación entre IMVI con el QTc y su dispersión. CONCLUSIÓN: El ECG es un método útil, eficaz y de alta reproductibilidad en el diagnóstico de HVI de los pacientes en HD. En esa población, el criterio de Producto de Cornell fue más fiable para la detección de HVI.BACKGROUND: Left ventricular hypertrophy (LVH is an independent predictor of cardiovascular risk, and its characterization and prevalence in chronic renal disease (CRD should be further studied. OBJECTIVE: To establish the diagnosis of LVH in patients with stage-5 CRD using six different electrocardiographic criteria, and to correlate them with left ventricular mass index (LVMI as obtained by echocardiography. METHODS: Cross-sectional study including 100 patients (58 men and 42 women, mean age 46.2 ± 14.0 years with CRD of all causes undergoing hemodialysis (HD for at least six months

  5. New frontiers in heart hypertrophy during pregnancy.

    Li, Jingyuan; Umar, Soban; Amjedi, Marjan; Iorga, Andrea; Sharma, Salil; Nadadur, Rangarajan D; Regitz-Zagrosek, Vera; Eghbali, Mansoureh


    During Pregnancy, heart develops physiological left ventricular hypertrophy as a result of the natural volume overload. Previously we have characterized the molecular and functional signature of heart hypertrophy during pregnancy. Cardiac hypertrophy during pregnancy is a complex process that involves many changes including in the signalling pathways, composition of extracellular matrix as well as the levels of sex hormones. This review summarises the recent advances and the new frontiers in the context of heart hypertrophy during pregnancy. In particular we focus on structural and extracellular matrix remodelling as well as signalling pathways in pregnancy-induced physiological heart hypertrophy. Emerging evidence shows that various microRNAs modulate key components of hypertrophy, therefore the role of microRNAs in the regulation of gene expression in pregnancy induced hypertrophy is also discussed. We also review the role of ubiquitin proteasome system, the major machinery for the degradation of damaged and misfolded proteins, in heart hypertrophy. The role of sex hormones in particular estrogen in cardiac remodeling during pregnancy is also discussed. We also review pregnancy-induced cardiovascular complications such as peripartum cardiomyopathy and pre-eclampsia and how the knowledge from the animal studies may help us to develop new therapeutic strategies for better treatment of cardiovascular diseases during pregnancy. Special emphasis has to be given to the guidelines on disease management in pregnancy.

  6. The Obesity Associated Peptide Leptin Induces Hypertrophy in Neonatal Rat Ventricular Myocytes%瘦素(leptin)诱导新生大鼠心室肌细胞的肥厚

    张震; 惠汝太



  7. Amlodipine and atorvastatin improve ventricular hypertrophy and diastolic function via inhibiting TNF-α, IL-1β and NF-κB inflammatory cytokine networks in elderly spontaneously hypertensive rats.

    Lu, Jingchao; Liu, Fan; Chen, Fei; Jin, Yaqiong; Chen, Huiqiang; Liu, Demin; Cui, Wei


    This study aimed to examine the effects of amlodipine and atorvastatin alone or in combination on the regulation of inflammatory cytokines and the underlying mechanisms in elderly spontaneously hypertensive (SH) rats. The level of serum hs-CRP was detected with ELISA. The serum TNF-α and IL-1β levels were assessed by radioimmunity assay (RIA). Cardiac inflammatory cell infiltration was observed by HE staining. The protein levels of TNF-α, IL-1β, of NF-κB P65 and IκBα were detected by immunoblotting. The intracellular localization of NF-κB p65 was observed using immunohistochemistry. Amlodipine or atorvastatin obviously ameliorated the myocardial inflammatory cell infiltration in SH rats, which was further improved by combinatorial treatment with amlodipine and atorvastatin. Either amlodipine or atorvastatin decreased plasma IL-1β content in SH rats, but there was no significant difference when compared with untreated SH rats. However, the combination of amlodipine and atorvastatin significantly decreased plasma IL-1β level in SH rats. Moreover, amlodipine or atorvastatin intervention significantly reduced myocardial TNF-α and IL-1β protein levels in SH rats, which was further suppressed by the combination of amlodipine and atorvastatin. In addition, amlodipine or atorvastatin inhibited the activity of NF-κB signaling in SH rats, which was further suppressed by combinatorial treatment. Furthermore, amlodipine or atorvastatin restored the activity of IκB-α in SH rats, which was enhanced by combinatorial treatment. Our results demonstrated amlodipine and atorvastatin improved ventricular hypertrophy and diastolic function possibly through the intervention of TNF-α, IL-1β, NF-κB/IκB inflammatory cytokine network. Our study suggests that amlodipine combined with atorvastatin may have additive effect on inhibiting inflammatory response.

  8. Effects of potassium channel activators on transient inward current in guinea pig ventricular myocytes%钾通道激动剂对豚鼠心室肌动作电位及瞬间内向电流作用机制的探讨

    张宏艳; 范崇济; 李小梅; 邢淑华; 潘永祜; 陈静; 杨楠; 陈朝晖


    Objective To investigate the mechanism of ATP-sensitive potassium channel(KATP) activator cromakaliam(CRK)on action potentials and transient inward current(Iti)in isolated guinea pig papillary and ventricular myocytes and to explore the mechanisms of effects of Iti and KATP treatment in idiopathic ventricular tachycardia.Methods The whole-cell patch clamp recording technique was used to detect the action potentials and Iti and KATP current alterations during the stimulated and triggered activity. Myocytes were isolated from guinea pig ventricle by enzyme digestion.The experiment was divided into four groups:(1)Control;(2)Control+Ouabain;(3)Control+CRK;(4)Control+Ouabain+CRK.(5) Control+Ouabain+CRK+glibenclamide(GLB).The action potential of guinea pig papillary muscules was measured by using standard microelectrode.The parameters in the experimant incluced the amplitude (APA),resting potentials(RP),action potentials duration(APD),as well as maximum rise of the action potential(Vmax).Results (1)When the guinea pig ventricular papillary myocytes were pretreated with Ouabain 0.5~mol/L,APD prolonged significantly,especially APD20,APD50,APD90.Delayed after depotorazion(DAD)and triggered activity were elicited.Iti currents and DAD as well as triggered activity increased.Iti current was(126.9±10.8)pA,lagT(1173.0±70.9)ms(n=10,P<0.01).(2)When guinea pig ventricular myocytes were pretreated with CRK(10 umol/L),APD was shortened and the amplitude of DAD was lowered.The coupling time in CRK group was significantly prolonged compared with Ouabain group(n=10,P<0.01).(3)CRK 50umol/L pretreatment of the ventricular myocytes led to an increase of KATP up to(342±89)pA,which was statistically significant as compared with the control group(P<0.01).ATP-sensitive potassium channel blocker glibeclamide(10umol/L)could antagonize the effects of CRK on APD and Iti currents.Conciusion CRK might reduce the toxic effect of Ouabain on cardiomyocytes,shorten APD,terminate DAD and trigger

  9. Carbachol augments Na/Ca exchange current via M2 muscarinic receptors in guinea pig ventricular myocytes%氨甲酰胆碱通过M2毒蕈碱受体增加豚鼠心肌细胞钠钙交换电流

    崔香丽; 陈还珍; 武冬梅; 吴博威


    Stimulation of cardiac mAChRs by carbachol (CCh) produces a biphasic inotropic response. The mechanisms of the positive inotropic response by higher concentration of CCh appear to be paradoxical. This article was aimed to study the mechanism of the positive inotropic effect of CCh in guinea pig ventricular myocytes. The effects of CCh on L-type calcium current (ICa) and Na/Ca exchange current (INa/Ca) were observed in voltage-clamped guinea pig ventricular myocytes by using Axon 200A amplifier. The results showed that CCh (100 μmol/L) increased both forword mode and reverse mode INa/Ca from (1.2±0.1) pA/pF to (2.0±0.3) pA/pF for forward mode (P<0.01) and from (1.3+0.5) pA/pF to (2.1+0.8) pA/pF for reverse mode (P<0.01), respectively. CCh had no effect on ICa. The stimulating effect of CCh on INa/Ca could be blocked by application of atropine, a nonselective blocker of muscarinic receptors,which means that the stimulating effect of CCh is through the activation of muscarinic receptors. We made a further study by using methoctramine, a selective antagonist of M2 muscarinic receptors. It completely abolished INa/Ca induced by 100 μmol/L CCh, indicating that the effect of CCh on INa/Ca was mediated by M2 muscarinic receptors. It is generally accepted that contraction in cardiac myocytes results from elevation of intracellular Ca2+ concentration. Ca2+ enters the cells through two pathways: L-type Ca2+ channels and, less importantly, reverse mode Na/Ca exchange. The calcium influx via both pathways promotes the contraction of cardiac myocytes.Because CCh had no effect on L-type Ca2+ current, the increase in Na/Ca exchange current might be the main factor in the positive inotropism of CCh. These results suggest that the positive inotropic effect of CCh in guinea pig heart is through stimulation of Na/Ca exchange and is mediated by M2 muscarinic receptors.%本文旨在研究氨甲酰胆碱(carbachol,CCh)对豚鼠心肌的正性变力性机制.用Axon200A膜片钳

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

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


    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

  11. Nuclear morphology and deformation in engineered cardiac myocytes and tissues.

    Bray, Mark-Anthony P; Adams, William J; Geisse, Nicholas A; Feinberg, Adam W; Sheehy, Sean P; Parker, Kevin K


    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease.

  12. Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

    Garciarena, Carolina D; Pinilla, Oscar A; Nolly, Mariela B; Laguens, Ruben P; Escudero, Eduardo M; Cingolani, Horacio E; Ennis, Irene L


    The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased approximately 40%, collagen volume fraction decreased approximately 50%, and capillary density increased approximately 45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100+/-19% versus 41+/-10% and 100+/-8% versus 61+/-9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca(2+) pump was significantly augmented, whereas that of Na(+)/Ca(2+) exchanger was unchanged (93+/-7% versus 167+/-8% and 158+/-13% versus 157+/-7%, sarcoplasmic reticulum Ca(2+) pump and Na(+)/Ca(2+) exchanger in SHR-Cs and SHR-Es, respectively; Peccentric model of cardiac hypertrophy (0.59+/-0.02 versus 0.53+/-0.01 in SHR-Cs and SHR-Es, respectively; Phypertrophy improving cardiac performance. The reduction of myocardial fibrosis and calcineurin activity plus the increase in capillary density represent factors to be considered in determining this beneficial effect.

  13. The Akt-mTOR axis is a pivotal regulator of eccentric hypertrophy during volume overload

    Masataka Ikeda; Tomomi Ide; Takeo Fujino; Yuka Matsuo; Shinobu Arai; Keita Saku; Takamori Kakino; Yasuhiro Oga; Akiko Nishizaki; Kenji Sunagawa


    The heart has two major modalities of hypertrophy in response to hemodynamic loads: concentric and eccentric hypertrophy caused by pressure and volume overload (VO), respectively. However, the molecular mechanism of eccentric hypertrophy remains poorly understood. Here we demonstrate that the Akt-mammalian target of rapamycin (mTOR) axis is a pivotal regulator of eccentric hypertrophy during VO. While mTOR in the heart was activated in a left ventricular end-diastolic pressure (LVEDP)-depende...

  14. Effects of 17-methoxyl-7-hydroxy-benzfuranchalcon on Intracellular Calcium Overload in Cultured Cardiac Myocytes of Neonatal Rats Injured by H2O2 and L-type Calcium Current in Isolated Ventricular Myocytes of Mice%17-甲氧基-7-羟基-苯并呋喃查尔酮对心肌细胞内游离钙浓度及L-型钙电流的影响

    李映新; 黄媛恒; 覃斐章; 林兴; 黄仁彬


    Objective:To investigate the effects of 17-methoxyl-7-hydroxy-benzfuranchalcon (YLSC) on intracellular calcium overload in cultured cardiac myocytes of neonatal rats injured by H2O2 and L-type calcium current (ICa-L) in isolated ventricular myocytes.Method:The cells of primary cultured cardiac myocytes of neonatal rats were divided into groups:①control group; ② model group:administrated with 0.3 mmol · L-1 H2O2; ③YLSC treated groups:incubation respectively with 100,200,400 μmol ·L-1 YLSC for 24 h,and add 0.3 mmol · L-1 H2O2.Laser confocal microscopy was used with Fluo-3/Am as indicator to detect changes of [Ca2+]i immediately and 15 mintues after H2O2 intervention.Single ventricular cell was obtained enzymatically by Langendorff perfusion apparatus.The wholecell patch clamp was used to record the ICa-L.Result:①The average fluorescence intensity values of the model group treated by H2O2 higher significantly than control group and the fluorescence enhancement ratio was 60.43 % ± 7.75%.The YLSC could decline the intensity values in a does-dependent manner manner,the fluorescence enhancement ratios of low,middle and high does respectively were 38.39% ±13.87%,14.49% ±2.94%,-28.1% ± 1.52%,and all of them were much lower compared with H2O2 group (P < 0.01).②YLSC can up-shifted the current-voltage (Ⅰ-Ⅴ) curves and markedly shifted the steady state activation and inactivation curve of ICa-L to the left.Conclusion:YLSC inhibited the L-type calcium channel,it can significantly reduce the myocardial intracellular Ca2+ overload induced by H2O2.%目的:研究17-甲氧基-7-羟基-苯并呋喃查尔酮(YLSC)对H2O2诱导的心肌细胞内钙超载的拮抗作用及对L型钙电流(ICa-L)的影响.方法:采用SD大鼠乳鼠进行心肌细胞培养,实验分为①正常对照组;②H2O2组:上机前加入终浓度为0.3 mmol·L-1的H2O2;③预先给予低、中、高不同终浓度YLSC药物处理组:分别给予100,200,400 μmol·L-1YLSC

  15. Asymptomatic cardiopulmonary changes caused by adenoid hypertrophy.

    Abdel-Aziz, Mosaad


    Adenoid hypertrophy is the most common cause of pediatric upper airway obstruction, and it can lead to cardiopulmonary complications such as pulmonary hypertension, cor pulmonale, and even heart failure. The aim of this study was to detect the asymptomatic cardiopulmonary changes that could happen in children with adenoid hypertrophy.Eighty children with adenoid hypertrophy were included in this study. Chest x-ray was used to assess the cardiothoracic ratio, whereas echocardiography was used for measuring the pulmonary arterial pressures, right ventricular diastolic filling parameters, and right ventricular end-diastolic diameters. All patients underwent adenoidectomy with or without tonsillectomy, and they were subjected again to echocardiographic assessment 6 months after the operation. No patient showed an increase in the cardiothoracic ratio on x-ray. Preoperative echocardiography showed an increase in pulmonary artery pressure (22.7 [SD, 3.8] mm Hg), a decrease in right ventricular diastolic filling parameters (E/A = 1.03 [SD, 0.17]), and an increase in right ventricular end-diastolic diameters (1.89 [SD, 0.19] cm). Postoperatively, pulmonary artery pressure decreased to 17.2 [SD, 2.1] mm Hg, right ventricular diastolic filling (E/A) increased to 1.25 [SD, 0.11], and right ventricular end-diastolic diameters decreased to 1.68 [SD, 0.12] cm. The comparison between preoperative and postoperative results for each individual parameter was statistically significant. Clinically asymptomatic cardiopulmonary changes due to adenoid hypertrophy are not rare. Early diagnosis and treatment of upper airway obstruction can prevent these serious complications. Echocardiographic examination should be recommended for these patients as a part of preoperative preparation to avoid anesthetic complications.


    周鑫洪; 王天游


    Objective To observe the effect of L - amlodipine besylate combined with benazepril in treatment of primary hypertension with left ventricular hypertrophy. Methods From March 2009 to March 2011,124 cases of primary hypertension with left ventricular hypertrophy patients were classified into two groups, in which the observation group of 62 cases were treated with L - amlodipine besylate combined with benazepril and control group of 62 cases were only treated with L - amlodipine besylate. The clinical effect between the two groups were compared. Results Compared with pretreatment, the levels of 24h systolic blood pressure ( SBP ) and 24h diastolic blood pressure ( DBP ) and the levels of interventricular septal thickness ( IVST ), posterior wall thickness ( PWT ), left ventricular end diastolic diameter ( LVDD ) and left ventricular mass index ( LVMI ) in observation group were significantly decreased( P <0. 05 ) after treatment, while only the levels of 24h SBP and 24h DBP were significantly decreased in control group ( P <0. 05 ). Moreover,the levels of 24h SBP and 24h DBP and the levels of IVST, PWT, LVDD and LVMI in observation group were significantly lower than those in control group( P <0. 05 ). Conclusion L - amlodipine besylate combined with benazepril in treatment of primary hypertension with left ventricular hypertrophy can lower blood pressure, and reverse left ventricular hypertrophy, which can be applied in clinic.%目的 观察苯磺酸左旋氨氯地平与贝那普利治疗原发性高血压伴左心室肥厚的临床效果.方法 2009年3月-2011年3月,原发性高血压伴左心室肥厚患者124例随机分为2组,观察组62例采用苯磺酸左旋氨氯地平与贝那普利联合治疗,对照组62例仅采用苯磺酸左旋氨氯地平治疗,比较2组的治疗效果.结果 与治疗前比较,观察组治疗后24h收缩压、24h舒张压、舒张期室间隔厚度(interventricular septal thickness,IVST)、舒

  17. Carbachol exhibited positive inotropic effect on rat ventricular myocytes via M2 muscarinic receptors%氨甲酰胆碱通过M2胆碱能受体对大鼠心肌细胞发挥正性肌力作用

    崔香丽; 陈还珍; 吴博威


    为研究氨甲酰胆碱(carbachol,CCh)对大鼠心肌细胞的正性肌力作用机制,利用电压钳方法观察CCh对急性分离的单个大鼠心肌细胞L-型钙电流(ICa,L)和钠/钙交换电流(INa/Ca)的影响.细胞负载Fura-2/AM后,用离子成像系统测定场刺激下单个大鼠心肌细胞的钙瞬变和细胞缩短.结果表明,100 μmol/L CCh使正向INa/Ca从(1.18±0.57)pA/pF增加到(1.65±0.52)pA/pF(P<O.01),反向INa/Ca从(1.11±0.49)pA/pF增加到(1.53±0.52)pA/pF(P<0.01),但不影响ICa,L.阿托品(非选择性M胆碱受体拮抗剂)和methoctramine(选择性M2胆碱受体拮抗剂)可阻断这种增加作用.100 μmol/L CCh使钙瞬变从对照组的203.8±50.0增加到234.8±64.3,使细胞缩短从对照组的(3.00±0.67)μm增加到(3.55±1.21)μm.KB-R7943(选择性反向INa/Ca抑制剂)不影响钙瞬变和细胞缩短的基础水平,却完全阻断CCh引起的钙瞬变和细胞缩短的增加.尼卡地平(ICa,L抑制剂)抑制钙瞬变和细胞缩短.CCh在尼卡地平存在下仍可增加钙瞬变和细胞缩短值,提示其正性肌力作用是通过刺激钠/钙交换实现的.CCh不改变钙敏感性.阿托品和methoctramine阻断CCh的这种激动作用,说明CCh的正性肌力作用是通过M2受体实现的.以上结果提示,CCh对大鼠心肌细胞有正性肌力作用,这种作用是通过激动反向钠/钙交换实现,由M2受体介导.%The present study was aimed to investigate the positive inotropic mechanism of carbachol (CCh) on rat ventricular myocytes. The effects of CCh on L-type calcium current (ICa,L) and Na+/Ca2+ exchange current (INa/Ca) were investigated in isolated rat ventricular myocytes. After loading myocytes with Fura-2/AM, electrically triggered Ca2+ transient and cell shortening in single myocyte were measured simultaneously using ion imaging system with charge-coupled device (CCD) camera. CCh (100 μmol/L)increased INa/Ca in forward mode from (1.18±0.57) pA/pF in the conrol group to (1.65±0

  18. Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

    Ahmad, Ashfaq; Sattar, Munavvar A.; Azam, Maleeha; Abdulla, Mohammed H.; Khan, Safia A.; Hashmi, Fayyaz; Abdullah, Nor A.; Johns, Edward J.


    The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development. PMID:27191852

  19. Association of left ventricular hypertrophy with leukoaraiosis in elderly patients with hypertension%老年高血压病患者左心室肥厚 与脑白质疏松症的关系

    李庆华; 王菲; 王玉敏


    目的 探讨老年高血压病患者左心室肥厚和脑白质疏松症(LA)的关系。方法 138例老年高血压病患者,按有或无LA分为两组,并对其年龄、是否合并左心室肥厚、糖尿病、高胆固醇血症、吸烟史以及收缩压和舒张压水平、高血压病持续时间进行分析。结果 在单因素Logistic回归分析中,左心室肥厚、收缩压水平、高血压病持续时间及年龄均为LA的影响因素;在多因素条件Logistic 回归分析中,左心室肥厚仍为LA的危险因素之一(OR=2.771,95%CI值1.260~6.094;P<0.01)。结论 左心室肥厚为老年高血压病患者LA独立的危险因素。%Objective To investigate whether left ventricular hypertrophy(LVH) is a risk factor for leukoaraiosis(LA) in elderly persons with hypertension.Methods 138 hypertensive patients with or without LA were investigated.We analysed the clinical features such as the age, LVH, the duration of hypertention,systolic and diastolic blood pressure, diabetes mellitus, hypercholesterolemia and smoking.Results In the univariate analysis, the age, LVH, the duration of hypertention, systolic blood pressure were statistically significant risk factors of LA in elderly persons with hypertension.Multivariate analysis revealed that LVH was a significant risk factor when the age, the duration of hypertention, systolic blood pressure as covariates in a logistic model(OR=2.771;95%CI,1.260~6.049;P<0.01).Conclusion LVH is a risk factor for LA in elderly persons with hypertension.

  20. Physiologic Limits of Left Ventricular Hypertrophy in Elite Junior Football Athletes%青少年足球运动员左室肥厚的生理极限研究



    Objectives:This study was undertaken to define physiologic limits of left ventricular hypertrophy in elite football athletes. Methods: 60 elite football athletes and 60 healthy sedentary controls and 40 sundry items of similar age and gender underwent echocardiography. Results:Compared with controls, football athletes had greater absolute LVWT (9.5±1.7mm vs. 8.4±1.4mm;). Maximal LVWT exceeded predicted upper limits in 5 athletes (8.3%);however, only one trained male athletes had absolute LVWT>12 mm (1.7%). Each of the 5 athletes with a LVWT exceeding predicted limits also showed enlarged left ventricular cavity dimension (54.4±2.1 mm;range 52 to 60 mm). Female athlete had a LVWT>11 mm. Conclusions:Trained adolescent football athletes demonstrated greater absolute LVWT compared with nonathletes. Only a small proportion of athletes exhibited a LVWT exceeding upper limits, very rarely>12 mm, and then always with chamber enlargement. Hypertrophic cardiomyopathy should be considered strongly in any trained football male athlete with LVWT>12 mm(females>11mm).%目的:确定青少年足球运动员左室肥厚的生理极限值,预防运动员运动性猝死的发生风险。方法:采用超声心动仪检测60名优秀青少年足球运动员和60名年龄、性别类似的健康对照者及40名其他项目运动员的左心室厚度。结果:与对照组相比,青少年足球运动员的左心室壁厚度(LVWT)较大,为9.5±1.7 mm,对照组为8.4±1.4mm。其中5名运动员(8.3%)的最大LVWT超过了预测值的上限;只有1名男运动员的绝对LVWT值大于12mm(1.7%)。5名运动员的LVWT超过了预测限度,提示左心腔扩大(54.4±2.1mm;范围为52~60mm)。而女运动员LVWT值均小于11 mm。结论:与非运动员相比,有训练的青少年足球运动员的LVWT值更大。只有一小部分运动员的LVWT超过了上限,但少有大于12mm,而腔室一般都有扩大现象。提示,当有训练

  1. 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

    Antonio Carlos Cicogna


    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

  2. The Frank-Starling mechanism in vertebrate cardiac myocytes.

    Shiels, Holly A; White, Ed


    The Frank-Starling law of the heart applies to all classes of vertebrates. It describes how stretch of cardiac muscle, up to an optimum length, increases contractility thereby linking cardiac ejection to cardiac filling. The cellular mechanisms underlying the Frank-Starling response include an increase in myofilament sensitivity for Ca2+, decreased myofilament lattice spacing and increased thin filament cooperativity. Stretching of mammalian, amphibian and fish cardiac myocytes reveal that the functional peak of the sarcomere length (SL)-tension relationship occurs at longer SL in the non-mammalian classes. These findings correlate with in vivo cardiac function as non-mammalian vertebrates, such as fish, vary stroke volume to a relatively larger extent than mammals. Thus, it seems the length-dependent properties of individual myocytes are modified to accommodate differences in organ function, and the high extensibility of certain hearts is matched by the extensibility of their myocytes. Reasons for the differences between classes are still to be elucidated, however, the structure of mammalian ventricular myocytes, with larger widths and higher levels of passive stiffness than those from other vertebrate classes may be implicated.

  3. Nanoscale three-dimensional imaging of the human myocyte.

    Sulkin, Matthew S; Yang, Fei; Holzem, Katherine M; Van Leer, Brandon; Bugge, Cliff; Laughner, Jacob I; Green, Karen; Efimov, Igor R


    The ventricular human myocyte is spatially organized for optimal ATP and Ca(2+) delivery to sarcomeric myosin and ionic pumps during every excitation-contraction cycle. Comprehension of three-dimensional geometry of the tightly packed ultrastructure has been derived from discontinuous two-dimensional images, but has never been precisely reconstructed or analyzed in human myocardium. Using a focused ion beam scanning electron microscope, we created nanoscale resolution serial images to quantify the three-dimensional ultrastructure of a human left ventricular myocyte. Transverse tubules (t-tubule), lipid droplets, A-bands, and mitochondria occupy 1.8, 1.9, 10.8, and 27.9% of the myocyte volume, respectively. The complex t-tubule system has a small tortuosity (1.04±0.01), and is composed of long transverse segments with diameters of 317±24nm and short branches. Our data indicates that lipid droplets located well beneath the sarcolemma are proximal to t-tubules, where 59% (13 of 22) of lipid droplet centroids are within 0.50μm of a t-tubule. This spatial association could have an important implication in the development and treatment of heart failure because it connects two independently known pathophysiological alterations, a substrate switch from fatty acids to glucose and t-tubular derangement.

  4. Magnesium homeostasis in cardiac myocytes of Mg-deficient rats.

    Michiko Tashiro

    Full Text Available To study possible modulation of Mg(2+ transport in low Mg(2+ conditions, we fed either a Mg-deficient diet or a Mg-containing diet (control to Wistar rats for 1-6 weeks. Total Mg concentrations in serum and cardiac ventricular tissues were measured by atomic absorption spectroscopy. Intracellular free Mg(2+ concentration ([Mg(2+]i of ventricular myocytes was measured with the fluorescent indicator furaptra. Mg(2+ transport rates, rates of Mg(2+ influx and Mg(2+ efflux, were estimated from the rates of change in [Mg(2+]i during Mg loading/depletion and recovery procedures. In Mg-deficient rats, the serum total Mg concentration (0.29±0.026 mM was significantly lower than in control rats (0.86±0.072 mM after 4-6 weeks of Mg deficiency. However, neither total Mg concentration in ventricular tissues nor [Mg(2+]i of ventricular myocytes was significantly different between Mg-deficient rats and control rats. The rates of Mg(2+ influx and efflux were not significantly different in both groups. In addition, quantitative RT-PCR revealed that Mg deficiency did not substantially change mRNA expression levels of known Mg(2+ channels/transporters (TRPM6, TRPM7, MagT1, SLC41A1 and ACDP2 in heart and kidney tissues. These results suggest that [Mg(2+]i as well as the total Mg content of cardiac myocytes, was well maintained even under chronic hypomagnesemia without persistent modulation in function and expression of major Mg(2+ channels/transporters in the heart.

  5. miRNA-133与高血压左心室肥厚的相关性及预测价值%Relation and diagnosis of miRNA-133 for being used as a prediction target molecular marker of left ventricular hypertrophy with hypertension

    黄雨晴; 余雪菊; 李捷; 周颖玲; 陈纪言; 冯颖青


    目的:先前国内外实验研究均表明miRNA-133可通过调控RhoA蛋白、细胞分化周期蛋白-42、参与心脏发生的核因子基因和结缔组织生长因子的表达而影响高血压左心室肥厚,但是上述实验并没有在临床上验证 miRNA-133对高血压左心室肥厚的预测价值,因此本研究旨在验证miRNA-133对高血压左心室肥厚的预测价值。方法收集未服用降压药物且发生左心室肥厚的单纯高血压患者和年龄性别相匹配的正常人外周血浆-80℃保存,采用 RT-PCR 技术验证差异表达miRNA的稳定性;组间比较用t检验,采用受试者工作特征(ROC)曲线验证miRNA-133对高血压左心室肥厚的预测价值。结果66例高血压左心室肥厚和33例正常人入选,血压和左心室质量指数有统计学差异(P<0.05),而年龄、血脂等基线资料无统计学差异(P>0.05);RT-PCR结果显示miRNA-133在正常人和高血压左心室肥厚组相对表达量分别为0.04±0.005、0.30±0.44,差异有统计学意义(P<0.05);调整年龄、性别和体质量指数后,miRNA-133表达水平与左心室肥厚具有相关性(ORs=1.654,95%CI 1.273~2.146,P<0.05);miRNA-133对高血压心肌肥厚预测的ROC曲线下面积(AUC)为0.860(P=0.000),95%CI 0.786~0.934(P<0.05)。结论 miRNA-133对高血压左心室肥厚有较好的预测价值。%ObjectivePrevious experimental studies at home and abroad indicated that miRNA-133 had effect on left ventricular hypertrophy in hypertension by regulating and controlling RhoA protein, cell division cycle protein-42, participating in the heart of nuclear factor gene and the expression of connective tissue growth factor, but those experiments were not clinically validated in the miRNA-133 for the value of hypertensive left ventricular hypertrophy, so this study is to verify the predictive value of miRNA-133 to left ventricular hypertrophy in hypertension

  6. Status and risk factors of chronic kidney disease complicated by left ventricular hypertrophy%慢性肾脏病并发左室肥厚现况及其危险因素

    彭道有; 岳华; 何卫; 关彦军; 赵龙


    Objective: To explore the prevalence of left ventricular hypertrophy (LVH) and risk factors among patients with chronic kidney disease (CKD) at ages 40-75years.Methods: The medical records of 210 patients with CKD at the stage of 2-5, who were nephrology inpatients in our hospital and 40-75 years old, were analyzed retrospectively.Results: (1) The incidence of diastolic dysfunction was significantly higher than systolic dysfunction (79.1% VS 20.3% P=0.000); The detection rate of left atrial enlargement was significantly higher than that of left ventricular enlargement (46.5% VS 19.8% P=0.000); The detection rate of interventricular septum thickening(IVSH) was significantly higher than that of left ventricular posterior wall thickening(LVPWH) (43.0% VS 21.1% P=0.000); LVH prevalence (according to the formula) was significantly higher than IVSH prevalence (47.9% VS 35% P=0.001), LVH in females had significantly difference than that in male (73.2% VS 31.0% P=0.000).However, if applying a different diagnostic criteria for LVH, no significant differences (50% VS 34.5% P=0.068).(2) The systolic blood pressure(SBP), pulse pressure(PP), serum creatinine (Scr) in IVSH group were higher than those in non-IVSH.The serum phosphate in LVPWH group in addition to the above factors was still higher than those non-LVPWH group, but by subgroup analysis in CKD5 ,only the SBP compared with the control group was significantly different.In LVH group SBP, PP were higher than those non-LVH, and hemoglobin(Hb), body mass index(BMI) were lower than the control group.Logistic regression analysis indicated that only gender, BMI were statistically significant.Conclusion:(1) 40-75 years old CKD patients with high risk of cardiovascular disease, diagnosed by echocardiography with different diagnostic criteria, different conclusions of LVH may be drawn,but the highest positive rate of LVH is from the formula.(2) 40-75 years CKD patients, SBP, PP, anemia, BMI, female are

  7. Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptor-induced cardiomyocyte hypertrophy

    Da-li LUO; Jian GAO; Xiao-mei LAN; Gang WANG; Sheng WEI; Rui-ping XIAO; Qi-de HAN


    Aim: Intracellular Ca2+ plays pivotal roles in diverse cellular functions, including gene transcription that underlies cardiac remodeling during stress responses. However, the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the mediation of cardiac intracellular Ca2+ and hypertrophic growth remains elusive. Prior work with neonatal rat ventricular myocytes suggests that activation of IP3Rs may be linked to α1 adrenergic receptor (α1AR) increased stereotyped Ca2+ spark occurrence and global Ca2+ oscillations. Thus, we hypothesized that Ca2+ release through IP3Rs was necessary for α1AR-stimulated cardiac hypertrophy. Methods: We used myoinositol 1,4,5-trisphosphate hexakis (butyryloxymethyl) ester (IP3BM), a membrane-permeant ester of IP3, to activate IP3Rs directly, and Fluo 4/AM to measure intracellular Ca2+ signaling. Results: IP3BM (10μmol·L-1) mimicked the effects of phenylephrine, a selective agonist of α1AR, in increments in local Ca2+ spark release (especially in the perinuclear area) and global Ca2+ transient frequencies. More importantly, IP3R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C, abolished the IP3BM-induced Ca2+ responses, and significantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cell size, [3H] leucine incorporation and atrial natriuretic factor gene expression, during sustained (48 h) phenylephrine stimulation. Conclusion: These results, therefore, provide cellular mechanisms that link IP3R signaling to α1AR-stimulated gene expression and cardiomyocyte hypertrophy.

  8. Left ventricular remodeling after experimental myocardial cryoinjury in rats.

    Ciulla, Michele M; Paliotti, Roberta; Ferrero, Stefano; Braidotti, Paola; Esposito, Arturo; Gianelli, Umberto; Busca, Giuseppe; Cioffi, Ugo; Bulfamante, Gaetano; Magrini, Fabio


    The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation

  9. Myocardial hypertrophy induces carotid body hyperplasia.

    Sivridis, Efthimios; Pavlidis, Pavlos; Fiska, Aliki; Pitsiava, Dimitra; Giatromanolaki, Alexandra


    The carotid bodies tend to enlarge after long-standing cardiopulmonary disease. Our objective was to investigate whether cardiac hypertrophy is associated with carotid body hyperplasia. Fifteen autopsy cases with combined left and right ventricular hypertrophy were examined and compared with two control groups (16 cases). The study involved a meticulous dissection of carotid bifurcations, thin serial sections, and morphometric analysis of carotid body volume and cell types (progenitor, dark, light, and sustentacular). There was a significant increase in sustentacular cells in all individuals with cardiac hypertrophy, which was not drug-induced, and accompanied by a similar increase in carotid body volume. Dark or light cell accumulation was detected focally and only in three instances. It appears that the generalized sustentacular cell hyperplasia is the result of long-standing hypoxia, while a superimposed focal prominence of dark or light cells may be proliferative or metaplastic in nature and attributed to short-term hypoxia.


    钟明; 张运; 张薇; 卞继峰; 卜培莉; 耿昭; 钟敬泉; 赵静


    探讨继发性右室肥厚(RVH)患者心肌细胞内Ca2+超负荷及钙调蛋白mRNA和蛋白 质表达的变化。方法:采用三电极直流等离子体原子发射直读光电光谱法测定心肌细胞内Ca2+含量;采用RT-PCR和Western bbt法测定RVH患者和正常对照钙调蛋白mRNA和蛋白质表达的变化。结果:与正常对照组相比,RVH患者心肌细胞内Ca2+含量提高3倍以上〔(1025.67±414.71)ug/ml vs(270.86±109.24)μg/ml,P0.05);Ca2+ -ATPase的蛋白质表达明显低于对照组(0.78±0.09 vs 1.03±0.03,P0.05)。结论:RVH患者SR Ca2+ -ATPase mRNA和蛋白质表达减低及细胞膜L型Ca2+ 通道mRNA转录减低是导致心肌细胞内Ca2+ 超负荷和RVH发生的主要分子生物学机制。%To elucidate molecular mechanisms of the changes of calmodulin gene expression when Ca2+ is overload in cardic muscle cell of patients with secondary right ventricular hypertrophy(RVH). Methods: Ten patients with secondary RVH and 6 control subjects were randomly selected. The content of calci um was assayed by spectrocomparator. The mRNA amounts of these calmodulin genes including L-type calcium channel, sarcoplasmic reticular(SR) Ca2+ -ATPase, ryanodine receptor, calsequestrin and phospholamban were de tected by reverse transcription-polymerase chain reaction(RT-PCR) and normalized to the mRNA levels of actin. The protein levels of SR Ca2+ -ATPase and phospholamban were analyzed by Western blot analysis. Results:The content of calcium increased significantly in patients with RVH. RT-PCR analyses showed that the steady-state level of mRNA encoding the SR Ca2 +-ATPase and cardiac L-type calcium channel decreased significantly in pa tients with RVH(0.66±0.28 vs 1.09±0.11, P<0.05,0.72±0.21 vs 1.08±0.14, P<0.05 ). In contrast, no alterations at the mRNA level for SR phospholamban, ryanodine receptor,calsequestrin were observed in pa tients with RVH compared with those in control subjects. Protein level of SR Ca2+ -ATPase

  11. 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

    Sérgio Lamêgo Rodrigues


    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

  12. Study on Amlodipine Besylate and Benazepril Hydrochloride Tablets Mixture in Reducing Hypertension Atrial Fibrillation in Patients With Left Ventricular Hypertrophy%氨氯地平贝那普利片合剂减少高血压伴左室肥厚患者新发房颤的研究

    宋宏雁; 景江新; 方志敏; 钟小兰; 刘顺民; 陆云


    Objective To compare amlodipine benazepril tablet and single agent to reduce the morbidity of atrial ifbrillation of hypertension patients with left ventricular hypertrophy. Methods 256 patients with hypertension with left ventricular hypertrophy were randomly divided into three groups, amlodipine group (n=85), the benazepril tablet group (n=87), amlodipine benazepril mixture group (n=84), Course of treatment is 18 months. Before and after treatment, blood pressure and echocardiography, dynamic electrocardiogram inspection and new atrial fibrillation and adverse reactions occur were been recorded. Results After treatment, the numerical value of amlodipine benazepril mixture group of patients including diastolic blood pressure, systolic pressure, diastolic left ventricular wall thickness, left atrial diameter value lower than single drug group was obviously, (P<0.05). New af rate is lower than single drug group, incidence of adverse reactions obviously lower than single drug group. Conclusion Amlodipine benazepril tablet is an effective drug to treat hypertension with left ventricular hypertrophy, can obviously control the patient's blood pressure and reverse left ventricular hypertrophy and left atrial enlargement, more signiifcant effect and higher security, lower incidence of atrial ifbrillation.%目的:比较氨氯地平贝那普利片和单剂减少高血压伴左室肥厚患者新发房颤的效果。方法高血压伴左室肥厚患者256例随机分为三组,氨氯地平组(n=85),贝那普利片组(n=87),氨氯地平贝那普利合剂组(n=84),疗程均为18个月。治疗前后进行血压和超声心动图、动态心电图检查和记录新发房颤和不良反应发生情况。结果治疗后,氨氯地平贝那普利合剂组患者舒张压、收缩压、舒张末期左室后壁厚度、左房内径数值较单药组降低明显(P均<0.05);新发房颤率低于单药组,不良反应发生率低于单药组。结论氨

  13. 人参二醇组与三醇组皂甙对大鼠心室肌细胞钙通道阻滞作用的通道分析%Single channel analysis on calcium channel blockadeaction of panaxadioi and panaxatriol saponins on cul-tured rat ventricular myocytes

    张文杰; 钟国赣; 江岩; 王小明; 王中峰


    Wistar rat ventricular myocytes were isolated. Panaxadiol saponins 1 5 0 0 μg· ml-1, panaxatriol saponins 300 μg ·ml-1,verapamil 37.5 μg·ml-1, or BAY k 8644 5μmol ·L-1 were added into the bath solution separately. The single channel activities of L, T, and B type calcium channels were recorded before and after the administration,using voltage patch - clamp technique in cell -attached configuration. The calcium channel blockade effect of these 2 groups of ginseno-sides was authenticated verified. The mecha-nism existed in the decrease in both the open time and the open - state probability of the calcium channel.%分离Wistar大鼠乳鼠的心室肌细胞.向培养基中分别加入人参二醇组皂甙1500 μg·ml-1,人参三醇组皂甙300μg·ml-1,维拉帕米37.5μg·ml-1或BAY k 8644 5 μmol·L-1.用斑片钳的连细胞电压钳法,记录加药前后L,T,B三型钙通道的单通道活动.确证了这两组人参皂甙的钙通道阻滞作用.其作用机制在于使钙通道的开放时间缩短与开放概率减少.

  14. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas


    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...... 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....

  15. 老年慢性肾脏病患者左心室肥厚危险因素分析%The risk factors of left ventricular hypertrophy of the elderly with chronic kidney disease

    袁晓玲; 林利容; 何娅妮


    Objective To explore the risk factors of left ventricular hypertrophy (LVH)in elderly patients with chronic kidney disease (CKD)1 -4 stages.Methods 1 98 cases of hospitalized patients over 65 years old with CKD in 1 -4 stages were selected and divided into LVH group and non LVH group according to left ventricular mass index(LVMI).Collecting the 24 hours ambulatory blood pressure and laboratory indices to analyze risk factors of LVH in CKD 1 -2 stages and CKD 3-4 stages.Results (1 )In the 1 98 cases of elderly patients with CKD,58 cases with LVH accounted for 29.3%.The prevalence of LVH in CKD 1 -4 stages were 8.1 %,26.2%,36.8% and 60.0%,respectively(P <0.01 ). (2)Compared with non-LVH group,patients in CKD 1 -2 stages with LVH had higher diurnal and nocturnal systolic blood pressure (SBP),diastolic blood pressure (DBP),mean arterial pressure level (MBP)and nocturnal hypertension incidence.Patients in CKD 3-4 phstages with LVH had higher serum phosphorus, calcium phosphorus product,day and night SBP and non dipper blood pressure rhythm incidence(P <0.05). (3)Diurnal and nocturnal SBP,DBP,MBP and nocturnal hypertension had positive correlation with LVH in CKD 1 -2 stages.Diurnal and nocturnal SBP increasing,non dipper blood pressure rhythm and serum phosphorus,calcium phosphorus product had positively correlation with LVH in patients of CKD 3-4 stages (P <0.05).(4)Women,24h-MBP were the risk factors of LVH in patients with CKD 1 -2 stages.Blood phosphorus and nocturnal SBP were the risk factors of LVH in patients with CKD 3-4 stages.Conclusion LVH in elderly patients with CKD is common.SBP increasing,calcium and phosphorus metabolism,renal function impairment are the significant causes of LVH in the elderly with CKD.%目的:探讨老年慢性肾脏病(CKD)1~4期患者发生左心室肥厚(LVH)的危险因素。方法选取198例 CKD 1~4期年龄≥65岁患者,根据左心室质量指数(LVMI)分为 LVH 组与非 LVH 组。收集动态血压、

  16. 丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道的影响%Effect of Salvianolic Acid B and Tetrahydropalmatine on the L-type Calcium Channel of Rat Ventricular Myocytes

    孟红旭; 王宝; 刘建勋


    目的 观察单独及联合使用丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道的影响.方法 采用急性酶解分离法获得大鼠的单个心肌细胞,使用全细胞膜片钳技术记录钙通道电流.观察给药前后钙通道电流峰值(钙电流活化后峰值点与完全失活后电流轨迹的垂直距离)的变化.结果 单独使用丹酚酸B(1,10,100 μmol/L)对钙电流峰值的抑制率分别为:(25.3±16.4)%(n=4),(44.6±24.0)%(n=6),(86.0±20.4)%(n=4).单独使用延胡索乙素(10,30,100 μmol/L)对钙电流峰值的抑制率分别为:(22.2±6.4)%(n=5),(27.4±1.6)%(n=3),(51.0±23.0)%(n=9);联合使用丹酚酸B(1μmoL/L)和延胡索乙素(10 μmol/L)对钙通道电流峰值的抑制作用强于单独使用丹酚酸B(1 μmol/L)或延胡索乙素(10μmoL/L),差异有统计学意义(P<0.05);盐酸阿托品(14 mmoL/L)能够逆转延胡索乙素对L-型钙通道的抑制作用,而加强丹酚酸B的抑制作用.结论 丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道均有抑制作用,两者之间能够产生协同效应,并且这两种有效成分调控L-型钙通道的作用机制不同.%Objective To observe the effects of the separate and joint use of salvianolic acid B (SalB) and tetrahydropalmatine (THP) on the L-type calcium channel of rat ventricular myocytes. Methods Single isolated ventricular myocytes of rats were obtained using acute enzymolysis separation. The current of the L-type calcium channel was recorded using whole-cell patch clamp technique. Changes of the current peak value of the calcium channel (the vertical distance between the peak value point after activation of the calcium electric current and the electric current track after complete inactivation) were observed before and after medication. Results The inhibition rate of using SalB (at the dose of 1, 10, and 100 μmol/L) alone on the current peak value of the calcium channel was respectively (25. 3 ±16. 4)% (n=4

  17. Intervention of systolic pressure and left ventricular hypertrophy in rats under cold stress%冷应激下高血压大鼠收缩压和左室肥厚的干预

    孙传福; 王苏贵; 彭易根; 石岩; 杜叶平; 施国祥; 文通; 王云开; 苏海


    目的 观察不同药物对冷应激下自发性高血压大鼠收缩压(SBP)、左心室肥厚(LVH)的影响.方法 将40只10周龄雄性自发性高血压大鼠(160~200 g)于(20±1)℃实验室适应性饲养7d,随机分成5组(n=8),即对照组、冷应激对照组、美托洛尔组、氨氯地平组、贝那普利组.每周测量1次大鼠SBP、体重和心率;放血处死后,称量大鼠左心室重量(LVW),计算其左心室重量指数(LVWI,mg/g);放射免疫法测定血浆和心肌内皮素-1(ET-1)、血管紧张素Ⅱ(AngⅡ)浓度,化学法检测血浆和心肌NO浓度;用反转录聚合酶链式反应(RT-PCR)法检测组织中内皮素A受体mRNA表达.结果 与冷应激对照组比较,各用药组大鼠SBP于第5周开始明显降低(P<0.05).与对照组[(2.89±0.19) mg/g]比较,冷应激对照组大鼠LVWI[(3.38±0.27) mg/g]明显增加(P<0.05);与冷应激对照组比较,氨氯地平组LVWI[(2.98±0.28)mg/g]明显降低(P<0.05).与对照组[(129.3±17.8) μmol/L]比较,冷应激对照组大鼠血浆NO浓度[(104.9±19.5) μmol/L]明显减少(P<0.05);与冷应激对照组比较,各用药组血液NO浓度为明显增高,差异均有统计学意义(P<0.05).与对照组[(4.5±1.9) pg/100 mg]比较,冷应激对照组大鼠心肌ET-1[(6.3±1.5)pg/100mg]明显增加(P<0.05);与冷应激对照组比较,氨氯地平组ET-1[(4.4±1.0)pg/100 mg]明显减少(P<0.05).冷应激对照组心肌内皮素A受体mRNA表达(0.86±0.23)明显高于对照组(0.45±0.16),差异有统计学意义(P<0.01);与冷应激对照组比较,氨氯地平组内皮素A受体mRNA表达(0.41±0.14)明显减少,差异有统计学意义(P<0.01).结论 氨氯地平可以降低冷应激下自发性高血压大鼠的SBP升高,抑制LVH.%Objective To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress.Methods A total of 40 male spontaneously hypertensive

  18. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups.

    Golden, Honey B; Gollapudi, Deepika; Gerilechaogetu, Fnu; Li, Jieli; Cristales, Ricardo J; Peng, Xu; Dostal, David E


    Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FBs) serve as in vitro models for studying fundamental mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Both cell types are relatively easy to culture as monolayers and can be manipulated using molecular and pharmacological tools. Because NRVM cease to proliferate after birth, and FBs undergo phenotypic changes and senescence after a few passages in tissue culture, primary cultures of both cell types are required for experiments. Below we describe methods that provide good cell yield and viability of primary cultures of NRVM and FBs from 0 to 3-day-old neonatal rat pups.

  19. Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

    RUAN Yanfei; LIU Nian; ZHOU Qiang; LI Yang; WANG Lin


    Summary: The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P0.05). The lower IK,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

  20. Raf-mediated cardiac hypertrophy in adult Drosophila.

    Yu, Lin; Daniels, Joseph; Glaser, Alex E; Wolf, Matthew J


    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK) signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFR(A887T), Ras85D(V12) and Ras85D(V12S35), which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr) RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERK(D334N), which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for

  1. Raf-mediated cardiac hypertrophy in adult Drosophila

    Lin Yu


    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimension