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Sample records for ventricular myocyte hypertrophy

  1. Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

    Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

    1995-01-01

    Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

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

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

    2003-01-01

    Activation of mammalian sterile 20–like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity–dependent manner. In vivo, cardiac-specific overexpr...

  3. Structural basis for pathologic left ventricular hypertrophy.

    Weber, K T; Brilla, C G

    1993-05-01

    Left ventricular hypertrophy (LVH) is a major risk factor associated with the emergence of symptomatic congestive heart failure. Cardiac myocyte excitation-contraction coupling has been the biochemical focus in the search for insights into the impaired contractility, relaxation, and stiffness of the hypertrophied myocardium. Although hypertrophied myocytes are the hallmark of LVH, other aspects of myocardial structure may be altered to impair pump function--specifically an abnormal accumulation of connective tissue (interstitial fibrosis). Cardiac fibroblasts, which are nonmyocyte cells of the cardiac interstitium, synthesize and degrade collagen and, therefore, represent an important determinant of pathologic LVH. Significantly, this reactive fibrosis has been found not only in the pressure-overloaded hypertrophied left ventricle but also in the normotensive, nonhypertrophied right ventricle of animals with experimental hypertension. These findings suggest the involvement of a circulating substance that has access to the coronary circulation common to both ventricles. Based on in vivo studies that examined this hypothesis, it can be concluded that chronic elevation of circulating aldosterone, relative to sodium intake, is associated with myocardial fibrosis, which initially adversely alters diastolic function and ultimately systolic ventricular function. The mechanisms by which fibroblast collagen metabolism is invoked in this setting are under investigation. Elucidation of these mechanisms may prepare the way to the prevention as well as the reversal of myocardial fibrosis and, in turn, of pathologic LVH. PMID:8504584

  4. Rapid ventricular filling in left ventricular hypertrophy: II. Pathologic hypertrophy.

    Smith, V E; Schulman, P; Karimeddini, M K; White, W B; Meeran, M K; Katz, A M

    1985-04-01

    To define the extent of left ventricular ejection and filling abnormalities in patients with mild hypertension, a non-imaging nuclear probe was used to generate high resolution time-activity curves in 25 patients with an average systolic blood pressure of 154 +/- 20 mm Hg and diastolic pressure of 98 +/- 8 mm Hg. The hypertensive patients did not meet electrocardiographic criteria for left ventricular hypertrophy, and none had evidence of ischemic or other cardiac disease. Compared with 25 age-matched normal subjects who had average systolic and diastolic pressures of 123 +/- 10 and 79 +/- 8 mm Hg, respectively, the hypertensive patients had a significantly lower ejection rate (2.00 +/- 0.20 versus 2.34 +/- 0.36 end-diastolic counts/s for the control group, p less than 0.05) and ejection fraction (58 +/- 4.9 versus 62 +/- 4.4) (p less than 0.05). The hypertensive patients had a markedly lower average rapid left ventricular filling rate (1.87 +/- 0.32 versus 2.69 +/- 0.41 counts/s for the control group, p less than 0.001). Although there was a modest inverse relation between echocardiographic left ventricular mass index and filling rate in the hypertensive patients (r = -0.59, p less than 0.01), 4 of 12 hypertensive patients with normal left ventricular mass index had a depressed filling rate. All of the hypertensive patients with increased left ventricular mass index had an abnormal left ventricular filling rate (less than 1.89 end-diastolic counts/s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3156176

  5. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

    Urbanek, Konrad; Quaini, Federico; Tasca, Giordano; Torella, Daniele; Castaldo, Clotilde; Nadal-Ginard, Bernardo; Leri, Annarosa; Kajstura, Jan; Quaini, Eugenio; Anversa, Piero

    2003-01-01

    It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation re...

  6. 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

    2016-04-01

    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. PMID:26902968

  7. Echocardiographic assessment of ejection fraction in left ventricular hypertrophy

    Wandt, B; Bojo, L; Tolagen, K; Wranne, B

    1999-01-01

    OBJECTIVE—To investigate the value of Simpson's rule, Teichholz's formula, and recording of mitral ring motion in assessing left ventricular ejection fraction (EF) in patients with left ventricular hypertrophy.
DESIGN—Left ventricular ejection fraction calculated by Simpson's rule and by Techholz's formula and estimated by mitral ring motion was compared with values obtained by radionuclide angiography.
SETTING—Secondary referral centre.
PATIENTS—16 patients with left ventricular hypertrophy ...

  8. Echocardiographic left ventricular hypertrophy in Chinese endurance athletes.

    Lo, Y. S.; Chin, M K

    1990-01-01

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

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

    Tuan, Hoang-Trong Minh; Williams, George S.B.; Chikando, Aristide C.; SOBIE, ERIC A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

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

  10. Mechanisms of Ca²+ handling in zebrafish ventricular myocytes.

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

    2013-12-01

    The zebrafish serves as a promising transgenic animal model that can be used to study cardiac Ca(2+) regulation. However, mechanisms of sarcoplasmic reticulum (SR) Ca(2+) handling in the zebrafish heart have not been systematically explored. We found that in zebrafish ventricular myocytes, the action potential-induced Ca(2+) transient is mainly (80 %) mediated by Ca(2+) influx via L-type Ca(2+) channels (LTCC) and only 20 % by Ca(2+) released from the SR. This small contribution of the SR to the Ca(2+) transient was not the result of depleted SR Ca(2+) load. We found that the ryanodine receptor (RyR) expression level in zebrafish myocytes was ∼72 % lower compared to rabbit myocytes. In permeabilized myocytes, increasing cytosolic [Ca(2+)] from 100 to 350 nM did not trigger SR Ca(2+) release. However, an application of a low dose of caffeine activated Ca(2+) sparks. These results show that the zebrafish cardiac RyR has low sensitivity to the mechanism of Ca(2+)-induced Ca(2+) release. Activation of protein kinase A by forskolin increased phosphorylation of the RyR in zebrafish myocardium. In half of the studied cells, an increased Ca(2+) transient by forskolin was entirely mediated by augmentation of LTCC current. In the remaining myocytes, the forskolin action was associated with an increase of both LTCC and SR Ca(2+) release. These results indicate that the mechanism of excitation-contraction coupling in zebrafish myocytes differs from the mammalian one mainly because of the small contribution of SR Ca(2+) release to the Ca(2+) transient. This difference is due to a low sensitivity of RyRs to cytosolic [Ca(2+)]. PMID:23821298

  11. Altered distribution of ICa impairs Ca release at the t-tubules of ventricular myocytes from failing hearts.

    Bryant, Simon M; Kong, Cherrie H T; Watson, Judy; Cannell, Mark B; James, Andrew F; Orchard, Clive H

    2015-09-01

    In mammalian cardiac ventricular myocytes, Ca influx and release occur predominantly at t-tubules, ensuring synchronous Ca release throughout the cell. Heart failure is associated with disrupted t-tubule structure, but its effect on t-tubule function is less clear. We therefore investigated Ca influx and release at the t-tubules of ventricular myocytes isolated from rat hearts ~18weeks after coronary artery ligation (CAL) or corresponding Sham operation. L-type Ca current (ICa) was recorded using the whole-cell voltage-clamp technique in intact and detubulated myocytes; Ca release at t-tubules was monitored using confocal microscopy with voltage- and Ca-sensitive fluorophores. CAL was associated with cardiac and cellular hypertrophy, decreased ejection fraction, disruption of t-tubule structure and a smaller, slower Ca transient, but no change in ryanodine receptor distribution, L-type Ca channel expression, or ICa density. In Sham myocytes, ICa was located predominantly at the t-tubules, while in CAL myocytes, it was uniformly distributed between the t-tubule and surface membranes. Inhibition of protein kinase A with H-89 caused a greater decrease of t-tubular ICa in CAL than in Sham myocytes; in the presence of H-89, t-tubular ICa density was smaller in CAL than in Sham myocytes. The smaller t-tubular ICa in CAL myocytes was accompanied by increased latency and heterogeneity of SR Ca release at t-tubules, which could be mimicked by decreasing ICa using nifedipine. These data show that CAL decreases t-tubular ICa via a PKA-independent mechanism, thereby impairing Ca release at t-tubules and contributing to the altered excitation-contraction coupling observed in heart failure. PMID:26103619

  12. Endothelin-1-induced remodelling of murine adult ventricular myocytes.

    Viero, Cedric; Wegener, Silke; Scholz, Anke; Ruppenthal, Sandra; Tian, Qinghai; Tabellion, Wiebke; Kreinest, Michael; Laschke, Matthias W; Kaestner, Lars; Lipp, Peter

    2016-01-01

    The precise role of hormones binding to Gαq protein-coupled receptors (H-GαqPCRs) in chronic heart diseases remains poorly understood. To address this, we used a model of cultured adult rat ventricular myocytes stimulated with endothelin-1 (ET-1) or phenylephrine (PE) over a period of 8 days in vitro (DIV). Chronically treated cells showed an increased number of arrhythmogenic Ca(2+) transients when electrically paced at 0.5Hz. While their post-rest behaviour was preserved, from DIV6 onwards the amplitude of caffeine-evoked Ca(2+) transients was increased in hormone-treated cells, suggesting an elevated sarcoplasmic reticulum Ca(2+) load. The duration of electrically evoked global Ca(2+) transients gradually increased over the culturing time indicating decreased activity of processes removing cytosolic Ca(2+). In treated cells, spontaneous Ca(2+) sparks displayed smaller amplitudes from DIV6 onwards, and a slower decay period for PE (from DIV3) and for ET-1 (from DIV6). This cellular functional remodelling was associated with changes in gene expression: chronic ET-1 treatment decreased PKCγ transcripts, whereas PE increased PKCγ and SERCA2a transcripts as probed by qPCR. Western blot analysis confirmed the upregulation of PKCγ with PE. To study ET-1 receptor desensitization in vivo, osmotic minipumps containing either NaCl or ET-1 were implanted in mice and Ca(2+) signalling was studied in acutely isolated ventricular myocytes after 2 weeks of chronic treatment. Interestingly, while cellular responses to isoproterenol stimulation were preserved in ET-1 treated animals, the inotropic response of myocytes to ET-1 stimulation was abrogated. We therefore conclude that chronic stimulation of cardiac myocytes by H-GαqPCRs induces cellular remodelling of Ca(2+) cycling with altered PKCγ expression and promotion of arrhythmogenic cellular responses. PMID:26794932

  13. Mechanisms of reoxygenation injury in cultured ventricular myocytes.

    Quaife, R A; Kohmoto, O; Barry, W H

    1991-02-01

    To investigate factors contributing to reperfusion and reoxygenation myocardial injury, we exposed layers of cultured chick ventricular myocytes to severe hypoxia for up to 3 hours in the presence of 20 mM 2-deoxyglucose, zero glucose, and 5 mM pyruvate, and then exposed the myocytes to reoxygenation. Lactate dehydrogenase (LDH) release was moderately increased during 3 hours of hypoxia but was increased markedly during reoxygenation. Coincident changes in intracellular calcium concentration ([Ca2+]i) and cell motion were also measured during hypoxia and reoxygenation. During hypoxia, [Ca2+]i increased to more than 1 microM, and with reoxygenation, [Ca2+]i abruptly decreased slightly but remained elevated more than 1 microM. Cells developed a stable rigor after 30 minutes of hypoxia. Reoxygenation caused a marked hypercontracture within 5 minutes. Pretreatment of myocytes with either 2,3-butanedione monoxime, which inhibits Ca2(+)-dependent force development, or cyanide inhibited reoxygenation hypercontracture. LDH release after reoxygenation was also significantly reduced in the presence of 2,3-butanedione monoxime. Treatment of myocytes with superoxide dismutase and catalase during hypoxia also resulted in a decrease in LDH release during reoxygenation. We conclude that an abrupt increase in [Ca2+]i during reoxygenation does not account for reoxygenation injury. However, in the presence of elevated [Ca2+]i, reoxygenation and the resulting probable resynthesis of ATP causes [Ca2+]i-dependent myofilament crossbridge cycling, and the resulting hypercontracture contributes to myocyte damage. The generation of oxygen free radicals after reoxygenation also appears to contribute to cell injury in this system. PMID:1991375

  14. Transcription Factor CHF1/Hey2 Regulates Specific Pathways in Serum Stimulated Primary Cardiac Myocytes: Implications for Cardiac Hypertrophy

    Yu, Man; Xiang, Fan; Beyer, Richard P; Farin, Federico M; Bammler, Theo K.; Chin, Michael T

    2010-01-01

    We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy. To identify transcriptional pathways regulated by CHF1/Hey2, we cultured primary neonatal mouse cardiac myocytes from wild type and transgenic mice overexpressing CHF1/Hey2 and treated them with serum, a potent hypertrophic stimulus. We verified that overexpression of CHF1/Hey2 suppressed cardiac myocyte hypertrophy induced by serum and then determined tra...

  15. Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

    Cooper, G.; Kent, R.L.; Uboh, C.E.; Thompson, E W; Marino, T A

    1985-01-01

    The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differe...

  16. 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

    2015-08-25

    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. PMID:26300251

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

    Gerdts, Eva; Okin, Peter M; Boman, Kurt; Wachtell, Kristian; Nieminen, Markku S; Dahlöf, Björn; Devereux, Richard B

    2012-01-01

    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....

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

    Yang Zhen-Yu; Guo Su-xia; Sun Li-ping; Guo Tao; Li Xiao-rong; Wang Ru-xing; Yang Xiang-Jun; Jiang Wen-ping

    2010-01-01

    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 ...

  19. Multiscale Modeling of Calcium Cycling in Cardiac Ventricular Myocyte: Macroscopic Consequences of Microscopic Dyadic Function

    Gaur, Namit; Rudy, Yoram

    2011-01-01

    In cardiac ventricular myocytes, calcium (Ca) release occurs at distinct structures (dyads) along t-tubules, where L-type Ca channels (LCCs) appose sarcoplasmic reticulum (SR) Ca release channels (RyR2s). We developed a model of the cardiac ventricular myocyte that simulates local stochastic Ca release processes. At the local Ca release level, the model reproduces Ca spark properties. At the whole-cell level, the model reproduces the action potential, Ca currents, and Ca transients. Changes i...

  20. Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats: influence of maternal Mg2+ supplementation.

    Wold, L E; Norby, F L; Hintz, K K; Colligan, P B; Epstein, P N; Ren, J

    2001-01-01

    Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol- induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics itself. PMID:12213974

  1. L-Arginine currents in rat cardiac ventricular myocytes.

    Peluffo, R Daniel

    2007-05-01

    L-Arginine (L-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import L-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel L-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular L-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent L-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of L-Arg. The inward movement of Arg molecules was found to be passive and independent of Na(2+), K(2+), Ca(2+) and Mg(2+). The process displayed saturation and membrane potential (V(m))-dependent kinetics, with a K(0.5) for l-Arg that increased from 5 mm at hyperpolarizing V(m) to 20 mm at +40 mV. L-Lysine and L-ornithine but not D-Arg produced currents with characteristics similar to that activated by L-Arg indicating that the transport process is stereospecific for cationic L-amino acids. L-Arg current was fully blocked after brief incubation with 0.2 mm N-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y(2+) family of transporters is responsible for L-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold. PMID:17303641

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

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

    1998-01-01

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

  3. Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts.

    Gadeberg, Hanne C; Bryant, Simon M; James, Andrew F; Orchard, Clive H

    2016-01-15

    In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (INCX) and l-type Ca current (ICa) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca]i) was monitored simultaneously using fluo-4. INCX was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell INCX was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of INCX and ICa away from the T tubules to the cell surface and an increase in t-tubular INCX/ICa density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular INCX in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between INCX and [Ca]i, which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes. PMID:26566728

  4. YY1 Protects Cardiac Myocytes from Pathologic Hypertrophy by Interacting with HDAC5

    Sucharov, Carmen C.; Dockstader, Karen; McKinsey, Timothy A.

    2008-01-01

    YY1 is a transcription factor that can repress or activate the transcription of a variety of genes. Here, we show that the function of YY1 as a repressor in cardiac myocytes is tightly dependent on its ability to interact with histone deacetylase 5 (HDAC5). YY1 interacts with HDAC5, and overexpression of YY1 prevents HDAC5 nuclear export in response to hypertrophic stimuli and the increase in cell size and re-expression of fetal genes that accompany pathological cardiac hypertrophy. Knockdown...

  5. The three-dimensional arrangement of the myocytes in the ventricular walls

    Anderson, Robert H; Smerup, Morten Holdgaard; Sanchez-Quintana, Damian; Loukas, Marios; Lunkenheimer, Paul P

    2009-01-01

    tangential to the epicardial and endocardial borders, albeit with marked variation in the angulation relative to the ventricular equator. Correlation with measurements taken using force probes shows that these myocytes produce the major unloading of the blood during ventricular systole. The second population...

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

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    2014-01-01

    Roč. 65, č. 4 (2014), s. 497-509. ISSN 0867-5910 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.386, year: 2014

  7. 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)

    2000-01-01

    BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, 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.

  8. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

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

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

    Palade Philip T

    2010-11-01

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

  10. YY1 protects cardiac myocytes from pathologic hypertrophy by interacting with HDAC5.

    Sucharov, Carmen C; Dockstader, Karen; McKinsey, Timothy A

    2008-10-01

    YY1 is a transcription factor that can repress or activate the transcription of a variety of genes. Here, we show that the function of YY1 as a repressor in cardiac myocytes is tightly dependent on its ability to interact with histone deacetylase 5 (HDAC5). YY1 interacts with HDAC5, and overexpression of YY1 prevents HDAC5 nuclear export in response to hypertrophic stimuli and the increase in cell size and re-expression of fetal genes that accompany pathological cardiac hypertrophy. Knockdown of YY1 results in up-regulation of all genes present during fetal development and increases the cell size of neonatal cardiac myocytes. Moreover, overexpression of a YY1 deletion construct that does not interact with HDAC5 results in transcription activation, suggesting that HDAC5 is necessary for YY1 function as a transcription repressor. In support of this relationship, we show that knockdown of HDAC5 results in transcription activation by YY1. Finally, we show that YY1 interaction with HDAC5 is dependent on the HDAC5 phosphorylation domain and that overexpression of YY1 reduces HDAC5 phosphorylation in response to hypertrophic stimuli. Our results strongly suggest that YY1 functions as an antihypertrophic factor by preventing HDAC5 nuclear export and that up-regulation of YY1 in human heart failure may be a protective mechanism against pathological hypertrophy. PMID:18632988

  11. Tissue characteristics in left ventricular hypertrophy using magnetic resonance imaging

    For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T1 and T2 values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T1 and T2 images were calculated. The regional wall thickness (WT) and T1 and T2 values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T1 and T2 values were significantly decreased in systole (T1: 185.6±37.9 msec, T2: 24.4±6.3 msec, mean±SD) compared to those in diastole (T1: 249.2±56.7 msec, T2: 31.7±9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T1 values and WT (ASH: r = 0.80, p 2 values and WT (ASH: r = 0.58, p 1 values in the ASH group (343.4±40.5 msec) were significantly higher than those of the CH group (247.3±21.4 msec), although the mean wall thickness values were similar in both groups. The T1/WT and T2/WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T1 and T2 values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T1 and T2 values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension. (author)

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

    Katholi, Richard E.; Daniel M. Couri

    2011-01-01

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

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

    Yang Zhen-Yu

    2010-04-01

    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.

  14. 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

    2016-01-01

    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

  15. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

    Musaro, A.; McCullagh, K. J.; Naya, F. J.; Olson, E. N.; Rosenthal, N.

    1999-01-01

    Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

  16. [Pathophysiology of left ventricular hypertrophy in arterial hypertension].

    Vallotton, M B; Braconi-Quintaje, S; Lang, U

    1997-02-11

    The role of left ventricular hypertrophy as an independent risk factor for subsequent cardio-vascular events is well established, therefore the authors, in this brief review, describe the endocrine function of the heart and the role played by various factors, including hormones, in the development of cardiac remodeling during the course of hypertension. They then outline the present state of our knowledge concerning transmembrane signaling in the cardiomyocyte in response to an activation of specific receptors for vasoactive hormones of the renin-angiotensin II-aldosterone system. PMID:9139339

  17. Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

    Siedlecka, U; Arora, M.; Kolettis, T; Soppa, G. K. R.; J. Lee; Stagg, M. A.; Harding, S E; Yacoub, M. H.; Terracciano, C. M. N.

    2008-01-01

    Clenbuterol, a compound classified as a β2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomer...

  18. Effect of haloperidol on transient outward potassium current in rat ventricular myocytes

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Nováková, M.

    2006-01-01

    Roč. 550, - (2006), s. 15-23. ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA305/04/1385 Institutional research plan: CEZ:AV0Z20760514 Keywords : rat ventricular myocytes * transient outward current * haloperidol * whole-cell patch clamp Subject RIV: BO - Biophysics Impact factor: 2.522, year: 2006

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

    Bacharova, Ljuba; Estes, E Harvey; Bang, Lia E; Hill, Joseph A; Macfarlane, Peter W; Rowlandson, Ian; Schillaci, Giuseppe

    2011-01-01

    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...

  20. From Left Ventricular Hypertrophy to Dysfunction and Failure.

    Lazzeroni, Davide; Rimoldi, Ornella; Camici, Paolo G

    2016-02-25

    Left ventricular hypertrophy (LVH) is growth in left ventricular mass caused by increased cardiomyocyte size. LVH can be a physiological adaptation to strenuous physical exercise, as in athletes, or it can be a pathological condition, which is either genetic or secondary to LV overload. Physiological LVH is usually benign and regresses upon reduction/cessation of physical activity. Pathological LVH is a compensatory phenomenon, which eventually may become maladaptive and evolve towards progressive LV dysfunction and heart failure (HF). Both interstitial and replacement fibrosis play a major role in the progressive decompensation of the hypertrophied LV. Coronary microvascular dysfunction (CMD) and myocardial ischemia, which have been demonstrated in most forms of pathological LVH, have an important pathogenetic role in the formation of replacement fibrosis and both contribute to the evolution towards LV dysfunction and HF. Noninvasive imaging allows detection of myocardial fibrosis and CMD, thus providing unique information for the stratification of patients with LVH. (Circ J 2016; 80: 555-564). PMID:26853555

  1. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  2. Non-gated computed tomography of left ventricular hypertrophy

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

  3. How reliable is the electrocardiogram in detecting left ventricular hypertrophy in hypertension?

    Vijan, S G; Manning, G.; Millar-Craig, M. W.

    1991-01-01

    This paper assesses the sensitivity and specificity of the electrocardiogram in detecting left ventricular hypertrophy in 75 hypertensive patients. Each patient underwent a 12 lead electrocardiogram and echocardiogram. Left ventricular mass index, using echocardiogram, was calculated according to the Penn convention and left ventricular hypertrophy was assessed by standard electrocardiographic criteria. The electrocardiogram was found to be very specific but insensitive in the detection of le...

  4. Effects of trimetazidine on pHi regulation in the rat isolated ventricular myocyte.

    Lagadic-Gossmann, D.; Le Prigent, K.; Feuvray, D.

    1996-01-01

    1. We have examined the effects of trimetazidine (TMZ) on intracellular pH (pHi) regulation in rat isolated ventricular myocytes. pHi was recorded ratiometrically by use of the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy-seminaphtorhodafluor). 2. Following an intracellular acid load (induced by 10 mM NH4Cl removal), pHi recovery in HEPES-buffered Tyrode solution was significantly slowed down upon application of 0.3 mM TMZ only when myocytes were pretreated for 5 h 30 min (slowing by ap...

  5. Rate of diastolic Ca release from the sarcoplasmic reticulum of intact rabbit and rat ventricular myocytes.

    Bassani, R A; D.M. Bers

    1995-01-01

    The sarcoplasmic reticulum (SR) of cardiac myocytes loses Ca during rest. In the present study, we estimated the rest-dependent unidirectional Ca efflux from the SR in intact rabbit and rat ventricular myocytes. We determined the time course of depletion of the SR Ca content (assessed as the amount of Ca released by caffeine) after inhibition of the SR Ca-ATPase by thapsigargin. Before rest intervals in Na-containing, Ca-free solution, a 3-min preperfusion with 0Na,0Ca solution was performed ...

  6. Mechanical Effects on KATP Channel Gating in Rat Ventricular Myocytes

    Huang, Haixia; Liang, Lifang; LIU, PING; Wei, Hua; Sachs, Frederick; Niu, Weizhen; WANG, Wei

    2013-01-01

    Cardiac KATP channels link metabolism with electrical activity. They are implicated in arrhythmias, secretion of atrial natriuretic peptide and protection of the heart from hypertrophy and failure. These processes may involve mechanosensitivity. KATP channels can be activated by mechanical stimulation and disrupting the cortical actin increases the activity. We propose that KATP channels are modulated by local bilayer tension and this tension is affected by cortical F-actin. Here we measured ...

  7. Ventricular premature contraction in hypertrophic cardiomyopathy and essential hypertension with left ventricular hypertrophy

    In order to investigate the relationship of different morbid states of the hypertrophied myocardium to the appearance of ventricular premature contraction (VPC), we compared the VPC findings from Holter ECG with those of UCG and stress thallium-201 myocardial SPECT scintigraphy (stress scinti) in 31 patients with hypertrophic cardiomyopathy (HCM) and 20 with essential hypertension (HT). The HCM patients consisted of 21 with asymmetric hypertrophy (ASH), 3 with symmetric hypertrophy (SH), and 7 with apical hypertrophy (APH). We recognized positive findings on the stress scinti such as fixed perfusion defect (FD) or reversible perfusion defect (RD) in 11 patients (ASH 10, APH 1) out of 31 patients with HCM (35%). Positive findings were observed in only one patient out of 20 with HT (5%). We recognized a high grade VPC (grade 4a and 4b of Lown's criteria) in 8 of 11 scinti positive patients with HCM (ASH 7, APH 1)(73%), while high grade VPC appeared in 5 (all of them are ASH) out of 20 scinti negative patients with HCM (25%). Therefore, these findings suggest that high grade VPCs in HCM occur in relation to a myocardial perfusion defect. (author)

  8. Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular myocytes

    Ajiro, Yoichi; Saegusa, Noriko; Giles, Wayne R; Diana M. Stafforini; Spitzer, Kenneth W.

    2011-01-01

    Sodium-hydrogen exchanger (NHE), the principal sarcolemmal acid extruder in ventricular myocytes, is stimulated by a variety of autocrine/paracrine factors and contributes to myocardial injury and arrhythmias during ischemia-reperfusion. Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent proinflammatory phospholipid that is released in the heart in response to oxidative stress and promotes myocardial ischemia-reperfusion injury. PAF stimulates NHE in ...

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

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

    2000-01-01

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

  10. Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Ohlídalová, D.; Jansová, D.; Šimurdová, M.; Šimurda, J.

    2010-01-01

    Roč. 200, č. 4 (2010), s. 301-314. ISSN 1748-1708 Institutional research plan: CEZ:AV0Z20760514 Keywords : action potential * ethanol * rat ventricular myocyte Subject RIV: BO - Biophysics Impact factor: 3.138, year: 2010 http:// apps .isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=15&SID=Y1pmpi@7k2HPEc8ehEE&page=1&doc=1&colname=WOS

  11. Characterization of the inward-rectifying potassium current in cat ventricular myocytes

    1988-01-01

    Whole-cell membrane currents were measured in isolated cat ventricular myocytes using a suction-electrode voltage-clamp technique. An inward- rectifying current was identified that exhibited a time-dependent activation. The peak current appeared to have a linear voltage dependence at membrane potentials negative to the reversal potential. Inward current was sensitive to K channel blockers. In addition, varying the extracellular K+ concentration caused changes in the reversal potential and slo...

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

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

  13. Hypertension and left ventricular hypertrophy in liquidators of consequences of the Chernobyl nuclear accident

    Echocardiography was used for the study of prevalence of left ventricular hypertrophy in 839 liquidators of consequences of the Chernobyl accident. Prevalence of left ventricular hypertrophy (left ventricular myocardial mass 134 g/m2) was 10.3, 13.4 and 22.5 % in liquidators with normal blood pressure, borderline hypertension and hypertension, respectively. Liquidators with normal blood pressure had significantly greater left ventricular myocardial mass than normotensive men from general population while liquidators and non liquidators with hypertension had equal values of this parameter

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

    Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L; D'Souza, Maria; Leósdóttir, Margrét; Nilsson, Peter M; Olsen, Michael H

    2015-01-01

    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...

  15. Exercise body surface maps in patients with left ventricular hypertrophy

    For evaluating exercise-induced myocardial ischemia in patients with ECG finding of left ventricular hypertrophy (LVH) with ST-T change, we recorded the body surface maps (QRST area maps) from 87 lead points before and after exercise and studied the patterns of the subtraction QRST area maps (S-maps) subtracting preexercise from postexercise maps in comparison with the findings of stress thallium (Tl) scans in 35 patients with hyertrophic cardiomyopathy (HCM) and 9 patients with essential hypertension (EH). All 21 patients whose S-maps revealed small changes less than -40μ VS or an increase only on the anterior chest region shoued no significant findings on the stress Tl scan. There were clear positive findings on the stress Tl scan in 7 of 8 patients with HCM (88%) whose S-maps revealed negative changes greater than -40μ VS on the wide precordial region and in 6 of 8 patients with HCM (75%) whose S-maps revealed increases on the anterior chest region but also had accompanying negative changes greater than -40μ VS somewhere on the precordial region. These results suggest that exercise QRST area maps may be useful in the identification of exercise-induced myocardial ischemia, especially in patients with HCM whose ECG showed LVH with ST-T changes. However, there were no significant findings on the stress Tl scan in 6 of 7 patients with EH whose S-maps revealed negative changes greater than -40μ VS on the precordial surface the same as those of HCM. These results suggest that factors other than exercise-induced myocardial ischemia such as the autonervous system may influence the ST-T changes in the EH cases. The specific mechanisms responsible for ischemic changes in patients with LVH (especially in those with HCM) are not clear, although small vessel disease combined with myocardial hypertrophy or myocardial squeezing may be causative factors. (author)

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

    Eduardo Cantoni Rosa

    2002-04-01

    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 height (LVM/h. The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI: or = 30kg/m. RESULTS: The BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height 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 height allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

  17. 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

    2015-12-01

    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. PMID:26454162

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

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M; Ibsen, H; Nordestgaard, B G

    2010-01-01

    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)....

  19. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes.

    Bryant, Simon; Kimura, Tomomi E; Kong, Cherrie H T; Watson, Judy J; Chase, Anabelle; Suleiman, M Saadeh; James, Andrew F; Orchard, Clive H

    2014-03-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation-contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. PMID:24412535

  20. Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy cntribute to adverse LV remodeling

    Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Bax, Noortje A M; Coppiello, Giulia; Oosterlinck, Wouter; Balogh, Agnes; Papp, Zoltan; Bouten, Carlijn V. C.; Bartunek, Jozef; D'Hooge, Jan; Luttun, Aernout; Verbeken, Erik

    2013-01-01

    Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosi...

  1. Exercise body surface mapping in patients with left ventricular hypertrophy

    To evaluate exercise-induced myocardial ischemia in patients with electrocardiographic evidence of left ventricular hypertrophy (LVH), including ST·T changes, body surface maps (QRST area maps) were recorded using 87 lead points before and after exercise. The patterns of the subtraction QRST area maps (S-maps) were compared with the findings of stress thallium (Tl) scans in 31 patients with hypertrophic cardiomyopathy and in five with essential hypertension. All 18 patients whose S-maps revealed changes less than -40 μVS or only an increase over the anterior chest region showed no positive findings on the stress Tl scans. However, there were clearly positive findings on stress Tl scans in eight (89%) of nine patients whose S-maps revealed changes greater than -40 μVS over a wide precordial region or in six (67%) of nine patients whose S-maps revealed increases over the anterior chest region and had accompanying changes greater than -40 μVS somewhere over the precordial region. These results suggested that exercise QRST area maps could differentiate exercise-induced myocardial ischemia from LVH with ST·T changes. (author)

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

    V. N. Poptsov

    2012-05-01

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

  3. 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

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (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. PMID:25711828

  4. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

    Hamouda, N N; Sydorenko, V; Qureshi, M A; Alkaabi, J M; Oz, M; Howarth, F C

    2015-02-01

    In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 25 mg/dl, n = 21) compared to Controls (98 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 2.28 %, n = 37) and STZ (76.58 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 5.35 %, n = 16) myocytes compared to Controls (92.01 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats. PMID:25351341

  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; Bella, Jonathan N; Aurigemma, Gerard P; Papademetriou, Vasilios; Dahlöf, Björn; Aalto, Tapio; Ibsen, Hans; Rokkedal, Jens E; Devereux, Richard B

    2010-01-01

    Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension with...... account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling...

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

    Seyyed Mohsen Hosseini

    2014-01-01

    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.

  7. 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

    2016-01-01

    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. PMID:27165726

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

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

    2012-01-01

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

  9. 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; Dahlöf, B; Nieminen, M S; Papademetriou, V; Bella, J N; Ibsen, H; Rokkedal, J; Devereux, R B

    2000-01-01

    Abnormal left ventricular (LV) filling may exist in early stages of hypertension. Whether this finding is related to LV hypertrophy is currently controversial. This study was undertaken to assess relations between abnormal diastolic LV filling and LV geometry in a large series of hypertensive...... patients with electrocardiographic LV hypertrophy. M-mode, 2-dimensional, and pulsed Doppler echocardiographic recordings of mitral inflow velocity and isovolumetric relaxation time (IVRT) were obtained in 750 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiography...

  10. Cardiac Biomarkers and Left Ventricular Hypertrophy in Asymptomatic Hemodialysis Patients

    Reneta Yovcheva Koycheva

    2015-12-01

    Full Text Available BACKGROUND: Cardiac biomarkers are often elevated in dialysis patients showing the presence of left ventricular dysfunction. The aim of the study is to establish the plasma levels of high-sensitivity cardiac troponin T (hs TnT, precursor of B-natriuretic peptide (NT-proBNP and high sensitivity C-reactive protein (hs CRP and their relation to the presence of left ventricular hypertrophy (LVH in patients undergoing hemodialysis without signs of acute coronary syndrome or heart failure. MATERIAL AND METHODS: Were studied 48 patients - 26 men and 22 women. Pre and postdialysis levels of hs cTnT, NT-proBNP and hs CRP were measured at week interim procedure. Patients were divided in two groups according to the presence of echocardiographic evidence of LVH - gr A - 40 patients (with LVH, and gr B - 8 patients (without LVH. RESULTS: In the whole group of patients was found elevated predialysis levels of all three biomarkers with significant increase (p < 0.05 after dialysis with low-flux dialyzers. Predialysis values of NT-proBNP show moderate positive correlation with hs cTnT (r = 0.47 and weaker with hs CRP (r = 0.163. Such dependence is observed in postdialysis values of these biomarkers. There is a strong positive correlation between the pre and postdialysis levels: for hs cTnT (r = 0.966, for NT-proBNP (r = 0.918 and for hs CRP (r = 0.859. It was found a significant difference in the mean values of hs cTnT in gr. A and gr. B (0.07 ± 0.01 versus 0.03 ± 0.01 ng /mL, p < 0.05 and NT-proBNP (15,605.8 ± 2,072.5 versus 2,745.5 ± 533.55 pg /mL, p < 0.05. Not find a significant difference in hs CRP in both groups. CONCLUSIONS: The results indicate the relationship of the studied cardiac biomarkers with LVH in asymptomatic patients undergoing hemodialysis treatment.

  11. Purinergic facilitation of ATP-sensitive potassium current in rat ventricular myocytes

    Babenko, Andrey P; Vassort, Guy

    1997-01-01

    The effects of different purinergic agonists on the cardiac adenosine 5′-triphosphate (ATP)-sensitive potassium current (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 μM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 purinoceptor antagonist.The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation o...

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

    Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard; Spätjens, Roel L H M G; Sipido, Karin R; Vos, Marc A

    the deactivation is much faster, is still unclear. In this study the conditions under which accumulation occurs in canine ventricular myocytes were studied with regard to its physiological relevance in controlling action potential duration (APD). At baseline, square pulse voltage clamp experiments...... revealed that the accumulation of canine IKs could occur, but only at rather short interpulse intervals (<100 ms). With action potential (AP) clamp commands of constant duration (originally recorded at rate of 2 Hz), an accumulation was only found at interpulse intervals close to 0 ms. Transmembrane...

  13. Effects of propafenone on calcium current in guinea-pig ventricular myocytes.

    Delgado, C; Tamargo, J; Henzel, D.; Lorente, P.

    1993-01-01

    1. The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2. Propafenone, 10(-7) -5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (ICa) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak ICa at +10 mV was 5 x 10(-6) M. 3. The voltage-dependence of ICa inactivation was shifte...

  14. Effects of oleic acid on the high threshold barium current in seabass Dicentrarchus labrax ventricular myocytes

    Chatelier, Aurelien; Imbert, Nathalie; Zambonino, Jose-luis; Mckenzie, David; Bois, P.

    2006-01-01

    The present study employed a patch clamp technique in isolated seabass ventricular myocytes to investigate the hypothesis that oleic acid (OA), a mono-unsaturated fatty acid, can exert direct effects upon whole-cell barium currents. Acute application of free OA caused a dose-dependent depression of the whole-cell barium current that was evoked by a voltage step to 0 mV from a holding potential of -80 mV. The derived 50% inhibitory concentration (IC50) was 12.49 +/- 0.27 mu mol l(-1). At a con...

  15. Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release of Rat Left Atrial Myocytes Due to Elevated Afterload

    Zhang, Haifei; Cannell, Mark B.; Kim, Shang Jin; Watson, Judy J.; Norman, Ruth; Calaghan, Sarah C.; Orchard, Clive H.; James, Andrew F.

    2015-01-01

    Atrial remodeling due to elevated arterial pressure predisposes the heart to atrial fibrillation (AF). Although abnormal sarcoplasmic reticulum (SR) function has been associated with AF, there is little information on the effects of elevated afterload on atrial Ca2+-handling. We investigated the effects of ascending aortic banding (AoB) on Ca2+-handling in rat isolated atrial myocytes in comparison to age-matched sham-operated animals (Sham). Myocytes were either labelled for ryanodine receptor (RyR) or loaded with fluo-3-AM and imaged by confocal microscopy. AoB myocytes were hypertrophied in comparison to Sham controls (P<0.0001). RyR labeling was localized to the z-lines and to the cell edge. There were no differences between AoB and Sham in the intensity or pattern of RyR-staining. In both AoB and Sham, electrical stimulation evoked robust SR Ca2+-release at the cell edge whereas Ca2+ transients at the cell center were much smaller. Western blotting showed a decreased L-type Ca channel expression but no significant changes in RyR or RyR phosphorylation or in expression of Na+/Ca2+ exchanger, SR Ca2+ ATPase or phospholamban. Mathematical modeling indicated that [Ca2+]i transients at the cell center were accounted for by simple centripetal diffusion of Ca2+ released at the cell edge. In contrast, caffeine (10 mM) induced Ca2+ release was uniform across the cell. The caffeine-induced transient was smaller in AoB than in Sham, suggesting a reduced SR Ca2+-load in hypertrophied cells. There were no significant differences between AoB and Sham cells in the rate of Ca2+ extrusion during recovery of electrically-stimulated or caffeine-induced transients. The incidence and frequency of spontaneous Ca2+-transients following rapid-pacing (4 Hz) was greater in AoB than in Sham myocytes. In conclusion, elevated afterload causes cellular hypertrophy and remodeling of atrial SR Ca2+-release. PMID:26713852

  16. Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle's cycle.

    Fang, Yong-Hu; Piao, Lin; Hong, Zhigang; Toth, Peter T; Marsboom, Glenn; Bache-Wiig, Peter; Rehman, Jalees; Archer, Stephen L

    2012-01-01

    Right ventricular hypertrophy (RVH) and RV failure are major determinants of prognosis in pulmonary hypertension and congenital heart disease. In RVH, there is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly increasing GO improves RV function, demonstrating the susceptibility of RVH to metabolic intervention. However, the effects of RVH on fatty acid oxidation (FAO), the main energy source in adult myocardium, are unknown. We hypothesized that partial inhibitors of FAO (pFOXi) would indirectly increase GO and improve RV function by exploiting the reciprocal relationship between FAO and GO (Randle's cycle). RVH was induced in adult Sprague-Dawley rats by pulmonary artery banding (PAB). pFOXi were administered orally to prevent (trimetazidine, 0.7 g/L for 8 weeks) or regress (ranolazine 20 mg/day or trimetazidine for 1 week, beginning 3 weeks post-PAB) RVH. Metabolic, hemodynamic, molecular, electrophysiologic, and functional comparisons with sham rats were performed 4 or 8 weeks post-PAB. Metabolism was quantified in RV working hearts, using a dual-isotope technique, and in isolated RV myocytes, using a Seahorse Analyzer. PAB-induced RVH did not cause death but reduced cardiac output and treadmill walking distance and elevated plasma epinephrine levels. Increased RV FAO in PAB was accompanied by increased carnitine palmitoyltransferase expression; conversely, GO and pyruvate dehydrogenase (PDH) activity were decreased. pFOXi decreased FAO and restored PDH activity and GO in PAB, thereby increasing ATP levels. pFOXi reduced the elevated RV glycogen levels in RVH. Trimetazidine and ranolazine increased cardiac output and exercise capacity and attenuated exertional lactic acidemia in PAB. RV monophasic action potential duration and QTc interval prolongation in RVH normalized with trimetazidine. pFOXi also decreased the mild RV fibrosis seen in PAB. Maladaptive increases in FAO reduce RV function in PAB-induced RVH. pFOXi inhibit FAO, which increases GO and enhances RV function. Trimetazidine and ranolazine have therapeutic potential in RVH. PMID:21874543

  17. Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

    Luo, An-tao; Luo, Hong-Yan; Hu, Xin-wu; Gao, Lin-lin; Liang, Hua-Min; Tang, Ming; Hescheler, Jürgen

    2010-01-01

    Aim: To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I Ca,L) in rat ventricular myocytes. Methods: The whole-cell patch-clamp techniques were used to record I Ca,L in rat ventricular myocytes. Results: Hyposmotic challenge(∼220 mosmol/L) induced biphasic changes of I Ca,L, a transient increase followed by a sustained decrease. I Ca,L increased by 19.1%±6.1% after short exposure (within 3 min) to hyposmotic solution. On the contrar...

  18. Effects of trimetazidine on pHi regulation in the rat isolated ventricular myocyte.

    Lagadic-Gossmann, D.; Le Prigent, K.; Feuvray, D.

    1996-01-01

    1. We have examined the effects of trimetazidine (TMZ) on intracellular pH (pHi) regulation in rat isolated ventricular myocytes. pHi was recorded ratiometrically by use of the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy-seminaphtorhodafluor). 2. Following an intracellular acid load (induced by 10 mM NH4Cl removal), pHi recovery in HEPES-buffered Tyrode solution was significantly slowed down upon application of 0.3 mM TMZ only when myocytes were pretreated for 5 h 30 min (slowing by approximately 50%; P < 0.01). This effect of TMZ on pHi recovery was shown to be not only time- but also dose-dependent with a large, quickly reversible, effect obtained with 1 mM TMZ applied for 2-3 h (slowing by approximately 64%; P < 0.001). This slowing of pHi recovery was also associated with a decrease of the NH4+ removal-induced acidification. 3. Relationship between intracellular intrinsic buffering power (beta i) and pHi was assessed in absence or presence of TMZ (0.3 mM or 1 mM). As expected, beta i increased roughly linearly with a decrease in pHi in all cases. However, both concentrations of TMZ significantly increased beta i (by approximately 55 and 65% at pHi 7.1, respectively). 4. When Na+/H+ exchange was inhibited by dimethyl amiloride (DMA; 40 microM), trimetazidine (1 mM) did not change the H+ flux estimated at pHi 7.1 (0.31 +/- 0.03 mequiv l-1 min-1, n = 5, control, versus 0.30 +/- 0.025 mequiv l-1 min-1, n = 5, TMZ), ruling out any effect of TMZ on background acid loading. 5. Acid efflux carried by Na+/H+ exchange was significantly decreased only when myocytes were pretreated with 1 mM TMZ, for 2-3 h (JeH = 2.86 +/- 0.38 mequiv l-1 min-1, n = 26, control, versus 1.66 +/- 0.26 mequiv l-1 min-1, n = 10, TMZ, estimated at pHi 7.1; P < 0.05). 6. In conclusion, the present work demonstrates that, following an intracellular acid load in HEPES-buffered medium, trimetazidine slows down pHi recovery in rat isolated ventricular myocytes, primarily through an increase of beta i. An effect on Na+/H+ exchange is also detected but only after long-term incubation of the myocytes with TMZ. PMID:8851498

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

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

    2012-04-15

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

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

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

    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...... isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may preventthe development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility....

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

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

    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...... 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....

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

    Nadia Sánchez Torres

    2011-01-01

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

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

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

    2015-08-15

    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)

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

    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/m2 for women or ≥ 116 g/m2 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/m2 (± 28.5; 99.2 to 228.5 g/m2] 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)

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

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

    2012-04-15

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

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

    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.

  7. QT interval dispersion in chronic heart failure and left ventricular hypertrophy: relation to autonomic nervous system and Holter tape abnormalities.

    Davey, P. P.; Bateman, J.; Mulligan, I. P.; Forfar, C; C Barlow; Hart, G.

    1994-01-01

    OBJECTIVE--To study QT dispersion in left ventricular hypertrophy and chronic heart failure and to determine the relation to ventricular arrhythmias. SETTING--Investigational laboratory of a tertiary referral centre. STUDY DESIGN--Patients with left ventricular hypertrophy and normal systolic function (n = 14) and patients with chronic heart failure (n = 18) were matched with controls (n = 17). The QT dispersion was examined in relation to abnormalities in resting mechanical and autonomic fun...

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

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

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and...

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

    Westerhout, Cynthia M; Lauer, Michael S; Fu, Yuling; Wallentin, L; Armstrong, Paul W; Husted, Steen

    2007-01-01

    AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries...

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

    Julio lvarez

    2013-04-01

    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.

  11. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

    Lowes, B D; Minobe, W; Abraham, W T; Rizeq, M N; Bohlmeyer, T J; Quaife, R A; Roden, R L; Dutcher, D L; Robertson, A D; Voelkel, N F; Badesch, D B; Groves, B M; Gilbert, E M; Bristow, M R

    1997-11-01

    Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction. PMID:9410910

  12. Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular myocytes.

    Ajiro, Yoichi; Saegusa, Noriko; Giles, Wayne R; Stafforini, Diana M; Spitzer, Kenneth W

    2011-12-01

    Sodium-hydrogen exchanger (NHE), the principal sarcolemmal acid extruder in ventricular myocytes, is stimulated by a variety of autocrine/paracrine factors and contributes to myocardial injury and arrhythmias during ischemia-reperfusion. Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent proinflammatory phospholipid that is released in the heart in response to oxidative stress and promotes myocardial ischemia-reperfusion injury. PAF stimulates NHE in neutrophils and platelets, but its effect on cardiac NHE (NHE1) is unresolved. We utilized quiescent guinea pig ventricular myocytes bathed in bicarbonate-free solutions and epifluorescence to measure intracellular pH (pH(i)). Methylcarbamyl-PAF (C-PAF; 200 nM), a metabolically stable analog of PAF, significantly increased steady-state pH(i). The alkalosis was completely blocked by the NHE inhibitor, cariporide, and by sodium-free bathing solutions, indicating it was mediated by NHE activation. C-PAF also significantly increased the rate of acid extrusion induced by intracellular acidosis. The ability of C-PAF to increase steady-state pH(i) was completely blocked by the PAF receptor inhibitor WEB 2086 (10 μM), indicating the PAF receptor is required. A MEK inhibitor (PD98059; 25 μM) also completely blocked the rise in pH(i) induced by C-PAF, suggesting participation of the MAP kinase signaling cascade downstream of the PAF receptor. Inhibition of PKC with GF109203X (1 μM) and chelerythrine (2 μM) did not significantly affect the alkalosis induced by C-PAF. In summary, these results provide evidence that PAF stimulates cardiac NHE1, the effect occurs via the PAF receptor, and signal relay requires participation of the MAP kinase cascade. PMID:21949111

  13. Soy-derived isoflavones exert opposing actions on Guinea pig ventricular myocytes.

    Liew, Reginald; Williams, J Koudy; Collins, Peter; MacLeod, Kenneth T

    2003-03-01

    Soy-derived isoflavones appear to possess cardioprotective properties, although the precise nature of this protection and the particular isoflavones responsible remain unclear. We hypothesized that isoflavones may differ in their cardiac actions in view of their varying affinities for the estrogen receptor and differences in ability to inhibit tyrosine kinase. We investigated the direct effects of three closely related isoflavones, genistein, daidzein, and equol (a metabolite of daidzein formed by gut microflora), on the contractile function of isolated guinea pig ventricular myocytes. Genistein (10 and 40 microM) significantly increased cell shortening and the Ca(2+) transient (measured using indo-1). In contrast, equivalent concentrations of equol produced the opposite effect, decreasing cell shortening and the Ca(2+) transient, whereas daidzein was without effect. The opposing actions of genistein and equol were still observed in the presence of the specific estrogen receptor antagonist ICI 182,780 (10 microM). However, the stimulatory actions of genistein were markedly reduced in the presence of the potent phosphotyrosine phosphatase inhibitor, bpV(phen). Both genistein and equol significantly inhibited the peak L-type Ca(2+) current. We conclude that genistein and equol affect the contractile function of ventricular myocytes in opposing ways despite a common initial action of Ca(2+) current antagonism. These differences occur independently of the estrogen receptor but may be partly related to the unique actions of genistein as a tyrosine kinase inhibitor. Furthermore, isoflavone metabolites, such as equol, may be more biologically active than their precursors and have a greater role in cardioprotection than previously realized. PMID:12604673

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

    Matsui Hiroki

    2012-12-01

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

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

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

  16. The transcription factor myocyte enhancer factor-2 (MEF2) in cardiac hypertrophy and heart failure

    van Oort, R.J.

    2007-01-01

    The heart responds to stress signals by hypertrophic growth, which is the first step towards heart failure (HF). The genetic pattern underlying HF remains largely elusive. Although the transcription factor Myocyte Enhancer Factor-2 (MEF2) is known to be a common endpoint for several hypertrophic signaling pathways, its precise role in myocardial remodeling is unknown. To this end, we pursued comprehensive gain- and loss-of-function approaches for MEF2 transcriptional activity in heart muscle ...

  17. Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy

    In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program

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

    Walsh Michael

    2010-06-01

    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.

  19. Pathophysiologic assessment of left ventricular hypertrophy and strain in asymptomatic patients with essential hypertension

    To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality

  20. 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

    2015-12-01

    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 ?-catenin/cyclin D1 invitro. In this study, we investigated the possible functions and mechanisms of Wnt5a in HPH invivo. 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 ?-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 ?-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 ?-catenin/cyclin D1 signaling. A therapy targeting the ?-catenin/cyclin D1 signaling pathway might be a potential strategy for HPH treatment. PMID:25956683

  1. Metal particulate matter components affect gene expression and beat frequency of neonatal rat ventricular myocytes.

    Graff, Donald W; Cascio, Wayne E; Brackhan, Joseph A; Devlin, Robert B

    2004-05-01

    Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into the bloodstream and transported to the heart where they might induce the expression of inflammatory cytokines and remodel electrical properties. We exposed cultured rat ventricular myocytes to similar concentrations of two metals [zinc (Zn) and vanadium (V)] found commonly in PM and measured changes in spontaneous beat rate. We found statistically significant reductions in spontaneous beat rate after both short-term (4-hr) and long-term (24-hr) exposures, with a more substantial effect seen with Zn. We also measured the expression of genes associated with inflammation and a number of sarcolemmal proteins associated with electrical impulse conduction. Exposure to Zn or V (6.25-50 microM) for 6 hr produced significant increases in IL-6, IL-1 alpha, heat shock protein 70, and connexin 43 (Cx43). After 24 hr exposure, Zn induced significant changes in the gene expression of Kv4.2 and KvLQt (potassium channel proteins), the alpha 1 subunit of the L-type calcium channel, and Cx43, as well as IL-6 and IL-1 alpha. In contrast, V produced a greater effect on Cx43 and affected only one ion channel (KvLQT1). These results show that exposure of rat cardiac myocytes to noncytotoxic concentrations of Zn and V alter spontaneous beat rate as well as the expression of ion channels and sarcolemmal proteins relevant to electrical remodeling and slowing of spontaneous beat rate, with Zn producing a more profound effect. As such, these data suggest that the cardiac effects of PM are largely determined by the relative metal composition of particles. PMID:15159208

  2. Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes.

    Shutt, Robin H; Howlett, Susan E

    2008-09-01

    Components of excitation-contraction (EC)-coupling were compared at 37 degrees C and 22 degrees C to determine whether hypothermia altered the gain of EC coupling in guinea pig ventricular myocytes. Ca(2+) concentration (fura-2) and cell shortening (edge detector) were measured simultaneously. Hypothermia increased fractional shortening (8.3+/-1.7 vs. 2.6+/-0.3% at 37 degrees C), Ca(2+) transients (157+/-33 vs. 35+/-5 nM at 37 degrees C), and diastolic Ca(2+) (100+/-9 vs. 60+/-6 nM at 37 degrees C) in field-stimulated myocytes (2 Hz). In experiments with high-resistance microelectrodes, the increase in contractions and Ca(2+) transients was accompanied by a twofold increase in action potential duration (APD). When voltage-clamp steps eliminated changes in APD, cooling still increased contractions and Ca(2+) transients. Hypothermia increased sarcoplasmic reticulum (SR) Ca(2+) stores (83+/-17 at 37 degrees C to 212+/-50 nM, assessed with caffeine) and increased fractional SR Ca(2+) release twofold. In contrast, peak Ca(2+) current was much smaller at 22 degrees C than at 37 degrees C (1.3+/-0.4 and 3.5+/-0.7 pA/pF, respectively). In cells dialyzed with sodium-free pipette solutions to inhibit Ca(2+) influx via reverse-mode Na(+)/Ca(2+) exchange, hypothermia still increased contractions, Ca(2+) transients, SR stores, and fractional release but decreased the amplitude of Ca(2+) current. The rate of SR Ca(2+) release per unit Ca(2+) current, a measure of EC-coupling gain, was increased sixfold by hypothermia. This increase in gain occurred regardless of whether cells were dialyzed with sodium-free solutions. Thus an increase in EC-coupling gain contributes importantly to positive inotropic effects of hypothermia in the heart. PMID:18614812

  3. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

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

    Chiranjivi Potu

    2012-02-01

    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.

  5. On the mechanism of rectification of the isoproterenol-activated chloride current in guinea-pig ventricular myocytes

    1993-01-01

    The whole cell configuration of the patch clamp technique was used to investigate the mechanism underlying rectification of the isoproterenol- activated chloride (Cl-) current in isolated guinea pig ventricular myocytes. When extracellular Cl- was replaced with either bromide (Br- ), glutamate (Glut), iodide (I-), isethionate (Iseth), or nitrate (NO3- ), the magnitude of the shift in reversal potential of the macroscopic current suggested the following selectivity sequence: NO3- > Br- > or = ...

  6. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes

    Bryant, Simon; Kimura, Tomomi E.; Kong, Cherrie H.T.; Watson, Judy J.; Chase, Anabelle; Suleiman, M. Saadeh; James, Andrew F; Orchard, Clive H

    2014-01-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation–contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC...

  7. Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?

    Pol, Christine J.; Muller, Alice; Simonides, Warner S.

    2008-01-01

    Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signali...

  8. Estrogen Attenuates Left Ventricular and Cardiomyocyte Hypertrophy by an Estrogen Receptor-Dependent Pathway that Increases Calcineurin Degradation

    Donaldson, Cameron; Eder, Sarah; Baker, Corey; Aronovitz, Mark J; Weiss, Alexandra Dabreo; Hall-Porter, Monica; Wang, Feng; Ackerman, Adam; Karas, Richard H; Molkentin, Jeffery D; Patten, Richard D.

    2008-01-01

    Left ventricular (LV) hypertrophy commonly develops in response to chronic hypertension and is a significant risk factor for heart failure and death. The serine-threonine phosphatase, calcineurin (CnA), plays a critical role in the development of pathologic hypertrophy. Previous experimental studies in murine models show that estrogen limits pressure overload-induced hypertrophy; our purpose was to explore further the mechanisms underlying this estrogen effect. Wild type, ovariectomized femal...

  9. Degradation of [125I]-atrial natriuretic peptide by a soluble metallopeptidase isolated from rat ventricular myocytes

    Atrial natriuretic peptide is rapidly degraded by a soluble, heat labile peptidase isolated from ventricular myocytes. Degradation of [125I]-ANP is antagonized by unlabelled ANP, bradykinin, glucagon, 1,10-phenanthroline, PCMB, EDTA and the bacterial antibiotic bacitracin, but not by phenylmethylsulphonyl fluoride, aprotinin, phosphoramidon, E-64, amastatin or the ACE inhibitor SQ 20881 and bradykinin potentiator C. In addition neither bovine serum albumin nor caesin afforded any protection against degradation. Peptidase activity was optimal at pH values above 8.5. The peptidase is likely to be of intracellular origin and may contribute to the extensive ANP degradative activity found in various ventricular muscle preparations

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

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

  11. [Advances in the relationship between leptin and hypertensive-left ventricular hypertrophy].

    Hu, Didan; Xu, Tongtong; Li, Jing; Wang, Wenyan; Lu, Xiangwei

    2015-07-01

    Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance. PMID:26267697

  12. A clinical study of thallium-201 scintigraphy in hypertensive patients with and without left ventricular hypertrophy

    Objective: Based on coronary angiography, thallium-201 myocardial scintigraphy was evaluated in hypertensive patients with and without left ventricular hypertrophy, and the causes of its perfusion abnormalities were discussed. Methods: Thallium-201 myocardial scintigraphy was performed on 85 patients with clinically suspected coronary artery disease. Coronary angiography was performed on patients with perfusion abnormalities in one month after scintigraphy. Results: The rate of 201Tl perfusion abnormalities in hypertensive patients with hypertrophy (85.7%) was higher than normal blood pressure (39.3%, P201Tl perfusion abnormalities occur in hypertensive patients with hypertrophy. The perfusion abnormalities may be caused not only by coronary large vessel disease, but also by coronary microvascular disease

  13. Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle’s cycle

    Fang, Yong-Hu; Piao, Lin; Hong, Zhigang; Toth, Peter T.; Marsboom, Glenn; Bache-Wiig, Peter; REHMAN, Jalees; Archer, Stephen L

    2011-01-01

    Right ventricular hypertrophy (RVH) and RV failure are major determinants of prognosis in pulmonary hypertension and congenital heart disease. In RVH, there is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly increasing GO improves RV function, demonstrating the susceptibility of RVH to metabolic intervention. However, the effects of RVH on fatty acid oxidation (FAO), the main energy source in adult myocardium, are unknown. We hypothesized that partial inhibitors of FAO (...

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

    Ching SM; Chia YC; Wan Azman WA

    2012-01-01

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

  15. Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription

    HUANG, HAIYAN; Joseph, Leroy C.; Gurin, Michael I.; Thorp, Edward B.; Morrow, John P.

    2014-01-01

    Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that Extracellular Signal-regulated Kinase (ERK) 1/2 activation during hypertrophy reduced SERCA2 transcription. Using a neonatal rat ventricular myocyte model of hypertrophy, we found that pharmacologic inhibitors of ERK activation ...

  16. A human ventricular myocyte model with a refined representation of excitation-contraction coupling.

    Himeno, Yukiko; Asakura, Keiichi; Cha, Chae Young; Memida, Hiraku; Powell, Trevor; Amano, Akira; Noma, Akinori

    2015-07-21

    Cardiac Ca(2+)-induced Ca(2+) release (CICR) occurs by a regenerative activation of ryanodine receptors (RyRs) within each Ca(2+)-releasing unit, triggered by the activation of L-type Ca(2+) channels (LCCs). CICR is then terminated, most probably by depletion of Ca(2+) in the junctional sarcoplasmic reticulum (SR). Hinch et al. previously developed a tightly coupled LCC-RyR mathematical model, known as the Hinch model, that enables simulations to deal with a variety of functional states of whole-cell populations of a Ca(2+)-releasing unit using a personal computer. In this study, we developed a membrane excitation-contraction model of the human ventricular myocyte, which we call the human ventricular cell (HuVEC) model. This model is a hybrid of the most recent HuVEC models and the Hinch model. We modified the Hinch model to reproduce the regenerative activation and termination of CICR. In particular, we removed the inactivated RyR state and separated the single step of RyR activation by LCCs into triggering and regenerative steps. More importantly, we included the experimental measurement of a transient rise in Ca(2+) concentrations ([Ca(2+)], 10-15 μM) during CICR in the vicinity of Ca(2+)-releasing sites, and thereby calculated the effects of the local Ca(2+) gradient on CICR as well as membrane excitation. This HuVEC model successfully reconstructed both membrane excitation and key properties of CICR. The time course of CICR evoked by an action potential was accounted for by autonomous changes in an instantaneous equilibrium open probability of couplons. This autonomous time course was driven by a core feedback loop including the pivotal local [Ca(2+)], influenced by a time-dependent decay in the SR Ca(2+) content during CICR. PMID:26200878

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

    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123I-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 201Tl 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 201Tl 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)

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

    Celso Ferreira Filho

    2010-01-01

    Full Text Available OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed, Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor and verapamil (Ca++ channel blocker caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker were similar. Indapamina (diuretic had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1 receptor antagonist produced better results than atenolol (selective β1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  19. [Left ventricular hypertrophy as a marker of adverse cardiovascular risk in persons of various age groups].

    Barsukov, A V; Glukhovskoĭ, D V; Zobnina, M P; Mirokhina, M A; Dydyshko, V T; Vasil'ev, V N; Kitsyshin, V P; Tishko, V V

    2014-01-01

    The paper considers modern conceptions about the prognostic value of left ventricular hypertrophy (LVH) different types. The role of interaction of demographic, hemodynamic, regulatory, intracardiac factors in the formation of prognostic peculiarities in patients with different types of LVH is marked. The data of own investigations indicating that the left ventricular myocardial mass has not less important value in long-term general prognostication than belonging to a concentric or eccentric LVH type in elderly patients with hypertension are presented. Some data concerning left atrial dilatation as an inalienable component of the cardiovascular continuum in essential hypertension are submitted. Pathogenic and prognostic contribution of metabolic disorders associated with hypertension and abdominal obesity in the development of the heart's left parts structural and functional disorders is shown. Issues of long-term outcome in elderly hypertensive patients with metabolic syndrome taking into account the peculiarities of left ventricular geometry are highlighted. PMID:25946857

  20. Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats

    Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 m Hg). After two weeks all were injected intravenously with 50 μCi of 201Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension

  1. PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy.

    Gollob, Michael H; Green, Martin S; Tang, Anthony S L; Roberts, Robert

    2002-05-01

    Genetic studies of families with inherited cardiac rhythm disturbances have established a molecular basis for ventricular arrhythmogenic disorders. Genes responsible for the long QT syndrome, Brugada syndrome, and polymorphic ventricular tachycardia have been identified. The elucidation of genetic defects responsible for more commonly occurring supraventricular rhythm disturbances have not been as forthcoming, with the exception of SCN5A mutations known to cause conduction system disease. Recently, we identified the genetic cause of a familial arrhythmogenic syndrome characterized by ventricular preexcitation and tachyarrhythmias (Wolff-Parkinson-White syndrome), progressive conduction system disease, and cardiac hypertrophy. The causative gene was shown to be the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase. The role of AMP-activated protein kinase in the regulation of the glucose metabolic pathway in muscle suggests that genetic defects in PRKAG2 may induce a previously undescribed cardiac glycogenosis syndrome. PMID:12015471

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

    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 specificity for each index were analyzed. The more sensitive the ECG criteria, the better the allometric fit. In conclusion: The allometric paradigm should be regarded as the way to design new and more sensitive ECG-based LVH markers.

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

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

    2011-12-01

    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.

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

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

    2000-01-01

    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)

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

    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 99mTc-methoxy-isobutyl isonitrile (MIBI) imaging and rest 123I-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 123I-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 123I-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 123I-BMIPP). Eighteen normotensive patients with apical defect by 123I-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 123I-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 123I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and 123I-BMIPP imaging are useful for the identification of these patients. (author)

  6. Phorbol ester and endothelin-1 alter functional expression of Na+/Ca2+ exchange, K+, and Ca2+ currents in cultured neonatal rat myocytes

    Puglisi, José L.; Yuan, Weilong; Timofeyev, Valeriy; Myers, Richard E.; Chiamvimonvat, Nipavan; Samarel, Allen M.; Bers, Donald M.

    2010-01-01

    Endothelin-1 (ET-1) and activation of protein kinase C (PKC) have been implicated in alterations of myocyte function in cardiac hypertrophy and heart failure. Changes in cellular Ca2+ handling and electrophysiological properties also occur in these states and may contribute to mechanical dysfunction and arrhythmias. While ET-1 or PKC stimulation induces cellular hypertrophy in cultured neonatal rat ventricular myocytes (NRVMs), a system widely used in studies of hypertrophic signaling, there ...

  7. 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

    2015-11-01

    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

  8. Normal pulmonary vascular resistance and left ventricular hypertrophy in young infants with bronchopulmonary dysplasia: an echocardiographic and pathologic study.

    Malnick, G; Pickoff, A S; Ferrer, P L; Peyser, J; Bancalari, E; Gelband, H

    1980-10-01

    To evaluate the cardiac anatomy and functional hemodynamics in young infants with chronic lung disease, nine patients, aged 2 to 7 months, with a clinical diagnosis of bronchopulmonary dysplasia (BPD) underwent echocardiographic examination. All infants required supplemental O2 (mean FIO2 35%) to maintain adequate systemic oxygenation (Pao2 greater than 50 mm Hg). None of the infants had evidence of a patent ductus arteriosus at the time of examination. Echocardiographic measurements of left and right ventricular systolic time intervals revealed normal systolic time interval ratios suggesting pulmonary vascular resistances. However, echocardiographic evidence of left ventricular hypertrophy was found in eight of the nine infants, while right ventricular anterior wall thickness and right ventricular diastolic dimensions were not increased. Two infants died; marked left ventricular hypertrophy was noted at the time of postmortem examination while the right ventricular wall thickness was normal. The findings of left ventricular hypertrophy led to a retrospective review of autopsy material of seven patients who died with BPD over the past year. In six of seven cases examined, left ventricular posterior wall thickening was noted (range 7 to 11 mm); while the right ventricular wall thickness was normal (range 2 to 5 mm). These data suggest that (1) as assessed by echocardiography, the pulmonary vascular resistance is not significantly elevated in young infants with BPD, and (2) a hypertrophic left ventricle evolves which may assume importance in the pathogenesis of pulmonary edema in BPD, though the precise etiology remains undetermined. PMID:6448973

  9. 123I-MIBG myocardial imaging in hypertensive patients. Abnormality progresses with left ventricular hypertrophy

    Twenty-seven patients with essential hypertension were prospectively studied with 123I-labeled metaiodobenzyl-guanidine (123I-MIBG) to assess the presence and location of impaired sympathetic innervation in hypertrophied myocardium. Thirteen patients had left ventricular hypertrophy on echocardiography, and 14 had normal echocardiograms. The wash-out ratio of 123I-MIBG in these two groups did not differ significantly (35.3±6.1 and 35.4±5.1) but was higher than in control subjects (29.4±6.7). The delayed heart-to-mediastinum count ratio was lower in the patients with hypertrophy than in the patients without hypertrophy (1.93±0.28 and 2.22±0.21; p<0.05) and the control subjects (1.93±0.28 and 2.33±0.25; p<0.05). On SPECT imaging, abnormalities in segmental uptake were frequent at the posterior and postero-lateral wall in both groups, although the hypertrophic group had more significant impairment. Our results lead to the hypothesis that hypertension in more advanced stages may be associated not only with hypertrophic changes but also with more advanced regional impairment of cardiac sympathetic innervation. (author)

  10. NOS1 induces NADPH oxidases and impairs contraction kinetics in aged murine ventricular myocytes.

    Villmow, Marten; Klöckner, Udo; Heymes, Christophe; Gekle, Michael; Rueckschloss, Uwe

    2015-09-01

    Nitric oxide (NO) modulates calcium transients and contraction of cardiomyocytes. However, it is largely unknown whether NO contributes also to alterations in the contractile function of cardiomyocytes during aging. Therefore, we analyzed the putative role of nitric oxide synthases and NO for the age-related alterations of cardiomyocyte contraction. We used C57BL/6 mice, nitric oxide synthase 1 (NOS1)-deficient mice (NOS1(-/-)) and mice with cardiomyocyte-specific NOS1-overexpression to analyze contractions, calcium transients (Indo-1 fluorescence), acto-myosin ATPase activity (malachite green assay), NADPH oxidase activity (lucigenin chemiluminescence) of isolated ventricular myocytes and cardiac gene expression (Western blots, qPCR). In C57BL/6 mice, cardiac expression of NOS1 was upregulated by aging. Since we found a negative regulation of NOS1 expression by cAMP in isolated cardiomyocytes, we suggest that reduced efficacy of β-adrenergic signaling that is evident in aged hearts promotes upregulation of NOS1. Shortening and relengthening of cardiomyocytes from aged C57BL/6 mice were decelerated, but were normalized by pharmacological inhibition of NOS1/NO. Cardiomyocytes from NOS1(-/-) mice displayed no age-related changes in contraction, calcium transients or acto-myosin ATPase activity. Aging increased cardiac expression of NADPH oxidase subunits NOX2 and NOX4 in C57BL/6 mice, but not in NOS1(-/-) mice. Similarly, cardiac expression of NOX2 and NOX4 was upregulated in a murine model with cardiomyocyte-specific overexpression of NOS1. We conclude that age-dependently upregulated NOS1, putatively via reduced efficacy of β-adrenergic signaling, induces NADPH oxidases. By increasing nitrosative and oxidative stress, both enzyme systems act synergistically to decelerate contraction of aged cardiomyocytes. PMID:26173391

  11. The evaluation of left ventricular eccentric hypertrophy by 201Tl-myocardial scintigraphy

    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. (author)

  12. 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

    2013-12-01

    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. PMID:24065618

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

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

  14. Hemodynamics, function and perfusion of the myocardium in arterial hypertensive with varying left ventricular hypertrophy

    Seventy eight patients with arterial hypertension were examined by echo-, radiocardiography and scintigraphy of the myocardium, using 99mTc pyrophosphate and 201Tl. A relationship was found between the development of hypertrophy of the left ventricle and the impairment of it perfusion and function. At the same time there was a correlation benween the decrease in cardiac output and the deterioration of myocardial blood supply. It was demonstrated that 99mTc pyrophosphate or 201Tl myocardial scintigraphy yielded the coincident results when relative heart failure was evaluated in patients with arterial hypertension and left ventricular hypertropy

  15. Diadenosine tetraphosphate-induced inhibition of ATP-sensitive K+ channels in patches excised from ventricular myocytes.

    Jovanovic, A.; Terzic, A

    1996-01-01

    Diadenosine 5',5''-P1,P4-tetraphosphate (Ap4A) has been termed 'alarmone' due to its role in intracellular signaling during metabolic stress. It is not known whether Ap4A could modulate ATP-sensitive K+ (KATP) channels, a family of channels regulated by the metabolic status of a cell. We applied the single-channel patch-clamp technique to measure the effect of Ap4A on KATP channels. When applied to the intracellular side of patches, excised from guinea-pig ventricular myocytes, Ap4A inhibited...

  16. Effects of acidosis and NO on nicorandil-activated KATP channels in guinea-pig ventricular myocytes

    Moncada, Gustavo A; Kishi, Yukio; Numano, Fujio; Hiraoka, Masayasu; Sawanobori, Tohru

    2000-01-01

    Nicorandil is a hybrid compound of K+ channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K+ channel (KATP) in guinea-pig ventricular myocytes using the patch-clamp technique.In whole-cell recordings, external application of 300 μM nicorandil activated KATP in the presence of 2 mM intracellular ATP concentration ([ATP]i) at external pH (pHo) 7.4, but the activated current was decreased by reducin...

  17. Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Jansová, D.; Šimurdová, M.; Nováková, M.; Šimurda, J.

    2009-01-01

    Roč. 380, č. 2 (2009), s. 125-133. ISSN 0028-1298 Institutional research plan: CEZ:AV0Z20760514 Keywords : perphenazine * antipsychotic drug * sodium current * transient outward current * rat ventricular myocytes Subject RIV: ED - Physiology Impact factor: 2.631, year: 2009 http:// apps .isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=T1JpdjJ8PNNeAL7D3il&page=1&doc=3&colname=WOS

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

    Chinali, M.; Simone, G. de; Wachtell, K.; Gerdts, E.; Gardin, J.M.; Boman, K.; Nieminen, M.S.; Papademetriou, V.; Dahlof, B.; Devereux, R.B.

    2008-01-01

    = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297......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...... 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...

  19. Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

    Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

    1998-01-01

    Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

  20. Evaluation of left ventricular hypertrophy using thallium-201 myocardial scintigraphy, echocardiography and vectorcardiography

    Thallium-201 (201Tl) myocardial scintigraphy was performed in 40 patients with left ventricular hypertrophy(LVH). Twelve out of 40 patients had pressure overloading (Aortic stenosis: 5, Hypertension: 7), 14 patients had volume overloading (Aortic regurgitation: 9, Mitral regurgitation: 5) and 14 had idiopathic cardiomyopathy (Hypertrophic type (HCM): 8, Congestive type (CCM): 6), respectively. LV area, LV uptake index and Wall uptake ratio were calculated from left anterior oblique view of 201Tl myocardial images. These three indices of both pressure overloading and volume overloading were significantly higher than those of controls. The degree of LVH was indicated by both LV area and LV uptake index. LV area was significantly larger in volume overloading than in pressure overloading. In idiopathic cardiomyopathy, these three indices of HCM and LV area and LV uptake index of CCM were significantly increased compared with those of controls. LV area of CCM was significantly larger than that of HCM, while Wall uptake ratio of HCM was significantly higher than that of CCM. LV uptake index and Wall uptake ratio of HCM became higher according as left ventricular cavity became smaller. LV area of CCM became larger in proportion as left ventricular cavity became larger and as left ventricular wall thickness became thinner. (author)

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

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

    2011-01-01

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

  2. Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction

    Warren Stafford G; Delgado Reynolds; Bauch Terry; Hayat Matthew J; Bungo Michael W; Rahman M; Vrtovec Bojan; Starc Vito; DePalma Jude L; Greco E; Feiveson Alan H; Kulecz Walter B; Schlegel Todd T; Núñez-Medina Tulio; Medina Rubén

    2010-01-01

    Abstract Background Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a ~5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods Resu...

  3. Different involvement of right ventricular myocardial function in either physiologic or pathologic left ventricular hypertrophy: a Doppler tissue study.

    D'Andrea, Antonello; Caso, Pio; Severino, Sergio; Sarubbi, Berardo; Forni, Alberto; Cice, Gennaro; Esposito, Nicolino; Scherillo, Marino; Cotrufo, Maurizio; Calabrò, Raffaele

    2003-02-01

    The aim of the study was to analyze right ventricular (RV) myocardial function in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HC) or athletic endurance training. Doppler echocardiography and pulsed Doppler tissue imaging of the posterior septal wall, and mitral and tricuspid annulus were performed in 32 top-level endurance athletes (AT) and in 27 patients with HC, all men. LV mass index was comparable between the 2 groups. All transmitral Doppler indexes were higher in AT, whereas only tricuspid inflow peak E and E/A ratio were slightly decreased in the HC group. In the HC group, Doppler tissue analysis showed lower myocardial systolic and early-diastolic (Em) peak velocities, and longer time intervals at the level of all the analyzed segments, even after correction for age, heart rate, and LV mass index. Distinct multiple linear regression models revealed an independent positive association between RV peak Em velocity and LV end-diastolic diameter (beta coefficient = 0.72, P <.0001) in AT, and an independent inverse correlation of the same peak Em velocity of tricuspid annulus with septal thickness (beta = - 0.65, P <.001) in the HC group. Of interest, a RV Em peak velocity < 0.16 m/s differentiated AT and HC groups better than tricuspid Doppler (89% sensitivity and 93% specificity). In conclusion, Em RV myocardial function is positively influenced by preload increase in AT and negatively associated to increased septal thickness in patients with HC. Therefore, Doppler tissue imaging may represent a useful tool in the differential diagnosis between athlete's heart and HC, underlining the different involvement of RV myocardial function in either physiologic or pathologic LV hypertrophy. PMID:12574742

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

    Bang, Casper N; Okin, Peter M; Køber, Lars; Wachtell, Kristian; Gottlieb, Alice Bendix; Devereux, Richard B

    2014-01-01

    BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value of...... 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...

  5. Xanthine Oxidase Inhibition with Febuxostat Attenuates Systolic Overload-induced Left Ventricular Hypertrophy and Dysfunction in Mice

    Xu, Xin; Hu, Xinli; Lu, Zhongbing; Zhang,Ping; Zhao, Lin; Wessale, Jerry L.; Bache, Robert J.; Chen, Yingjie

    2008-01-01

    The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mic...

  6. Differentiation of hypertrophic cardiomyopathy from left ventricular hypertrophy induced by essential hypertension using magnetic resonance imaging

    To examine the efficacy of magnetic resonance imaging (MRI) in diagnosing hypertrophic cardiomyopathy (HCM), 16 patients with HCM and 14 hypertensives with left ventricular hypertrophy (LDH) were studied using a 0.5 Tesla Siemens MRI apparatus equipped with cardiac gating. In HCM, left ventricular hypertrophy was localized to the septal wall in four, to the apical wall in two, to both the septal and apical walls in two, and to the apical and inferior walls in one, and it was diffuse in seven patients. In hypertensives, LVH was localized to the septal wall in three, to both the septal and anterior walls in two, to the free wall in one, and it was diffuse in eight patients. The distribution of the hypertrophic portion was nearly equal in both groups. The thickest portion of the left ventricular wall was 24.6 ± 4.8 mm in HCM and 21.6 ± 5.4 mm in hypertension, and there was no significant difference between them. The T2 relaxation time of the hypertrophic portion was 52.2 ± 4.8 msec in HCM and 45.3 ± 6.1 msec in hypertension, and there was a significant difference between them (p 2 relaxation times of the hypertrophic and non-hypertrophic protions in both groups. In conclusion, it may be difficult to differentiate HCM from hypertension based on the distribution of hypertrophic portions, but measurements of the T2 relaxation times may be useful for making the differential diagnosis. (author)

  7. Echocardiographic partition values and prevalence of left ventricular hypertrophy in hypertensive Nigerians

    Oladapo Olulola O

    2006-08-01

    Full Text Available Abstract Background Left ventricular hypertrophy (LVH is a well known independent risk factor for cardiovascular events. It has been shown that combination of left ventricular mass (LVM and relative wall thickness (RWT can be used to identify different forms of left ventricular (LV geometry. Prospective studies have shown that LV geometric patterns have prognostic implications, with the worst prognosis associated with concentric hypertrophy. The methods for the normalization or indexation of LVM have also recently been shown to confer some prognostic value especially in obese population. We sought to determine the prevalence of echocardiographic lLVH using eight different and published cut-off or threshold values in hypertensive subjects seen in a developing country's tertiary centre. Methods Echocardiography was performed in four hundred and eighty consecutive hypertensive subjects attending the cardiology clinic of the University college Hospital Ibadan, Nigeria over a two-year period. Results Complete data was obtained in 457 (95.2% of the 480 subjects (48.6% women. The prevalence of LVH ranged between 30.9–56.0%. The highest prevalence was when LVM was indexed to the power of 2.7 with a partition value of 49.2 g/ht2.7 in men and 46.7 g/ht2.7 in women. The lowest prevalence was observed when LVM was indexed to body surface area (BSA and a partition value of 125 g/m2 was used for both sexes. Abnormal LV geometry was present in 61.1%–74.0% of our subjects and commoner in women. Conclusion The prevalence of LVH hypertensive patients is strongly dependent on the cut-off value used to define it. Large-scale prospective study will be needed to determine the prognostic implications of the different LV geometry in native Africans.

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

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

  9. 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; Olsen, Michael Hecht; Ibsen, Hans; Opie, Lionel; Holm, Søren; Hesse, Birger

    2005-01-01

    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...

  10. 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

    2014-01-01

    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.

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

    Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi; Nordestgaard, Børge G; Kontula, Kimmo; de Faire, Ulf; Ibsen, Hans; Kjeldsen, Sverre; Os, Ingrid; Dahlöf, Björn

    2013-01-01

    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...

  12. Does reduced myocardial efficiency in systemic hypertensive-hypertrophy correlate with increased left-ventricular wall thickness?

    Han, June-Chiew; Barrett, Carolyn J; Taberner, Andrew J; Loiselle, Denis S

    2015-08-01

    Elevated systemic blood pressure, and the attendant development of pathologic left ventricular (LV) hypertrophy, ultimately culminates in heart failure and death. In clinical studies, a reduction of myocardial efficiency has been implicated in systemic hypertensive-hypertrophy. However, it is uncertain whether reduced efficiency correlates with LV wall thickness. Hence, we performed experiments on isolated working hearts of spontaneously hypertensive rats (SHRs)-a widely-used experimental model of human hypertensive-hypertrophy. We contrasted their mechanoenergetic performance with that of Wistar controls at two ages: Adult (9 months) and Aged (post-18 months). The use of animal hearts allowed us to perform experiments over a wide range of afterloads. We found that mechanoenergetic performance (coronary and aortic flows, work output and oxygen consumption) declined with age. The peak efficiency of the Adult SHR was essentially similar to that of Control, but that for the Aged SHR was lower, compared with that of age-matched Wistar rats. All variables, including peak efficiency, obtained from the failing Aged SHR hearts (which also developed right ventricular hypertrophy), were greatly reduced. Our data reveal that peak efficiency of the Aged SHR, upon transitioning from compensated hypertrophy to failure, diminishes sharply, arising from compromised flows-both aortic and coronary. We further show that the reduction of myocardial efficiency in hypertensive-hypertrophy does not correlate with LV wall thickness, but instead is inversely correlated with whole-heart mass. The latter relation may serve as a prognostic and diagnostic tool in the clinical setting. PMID:25787044

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

    Belcher, Scott M.; Chen, Yamei; Yan, Sujuan

    2012-01-01

    Previously we showed that 17β-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E2 on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10−12 m, and the most efficacious concentrations for each were at 10−9 m. Sensitivity to E2 and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E2 suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ERβ knockout mouse model showed that ERα and ERβ have opposing actions in myocytes and that the balance between ERβ and ERα signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E2 and BPA is dominated by the stimulatory ERβ-mediated signaling, and the absence of BPA and E2 responsiveness in males is due to a counterbalancing-suppressive action of ERα. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ERα and ERβ signaling. PMID:22166976

  14. Stilbene disulfonates block ATP-sensitive K+ channels in guinea pig ventricular myocytes.

    Furukawa, T; Virg, L; Sawanobori, T; Hiraoka, M

    1993-12-01

    Effects of stilbene disulfonates on single KATP channel currents were investigated in inside-out and outside-out membrane patches from guinea pig ventricular myocytes. All drugs tested, 4,4'-diisothiocyanatostilbene,2,2'-disulfonic acid (DIDS), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), and 4,4'-diaminostilbene-2,2'-disulfonic acid (DADS), inhibited the KATP channel when they were applied to the intracellular, but not extracellular side of the membrane patch. Inhibitory actions of DIDS and SITS were irreversible, whereas those induced by DNDS and DADS were reversible. KATP channel inhibition was concentration dependent with an order of potency of DIDS > SITS approximately DNDS > DADS; the Hill coefficient was close to unity for each drug. No change in channel conductance was observed during exposure to DIDS or DNDS; however, channel kinetics was altered. Distribution of the open time within bursts and that between bursts could be described by a single exponential relation in the absence and presence of DIDS or DNDS. The time constant of the open time within bursts was not altered, but that between bursts was decreased by DIDS (from 40.0 +/- 8.1 to 29.8 +/- 6.7 msec, P < 0.05) and by DNDS (from 43.1 +/- 9.3 to 31.9 +/- 7.1 msec, P < 0.05). Distributions of closed time within bursts were also fitted to a single exponential function both in the absence and presence of drugs, while those of the closed time between bursts were fitted to a single exponential function in the absence of drugs, but a double exponential function was required in the presence of drugs. The rates of onset and development of channel inhibition by DIDS and DNDS appeared to be concentration dependent; a longer time was required to reach a new steady-state of channel activity as drug concentration was decreased. Inhibition by DIDS or DNDS was regulated by intracellular pH; inhibition was greater during acidic conditions. For DIDS (0.1 mM), the open probability (Po) expressed as a fraction of the value before drug application was 42.9 +/- 8.3% at pH 7.4 and 8.2 +/- 6.6% at pH 6.5 (P < 0.01); corresponding values for DNDS (1 mM) were 39.6 +/- 17.6 and 8.9 +/- 5.8%, respectively (P < 0.01). From these data, we conclude that stilbene disulfonates block the KATP channel by binding to their target site with one-to-one stoichiometry. Similar to glibenclamide, the binding of stilbene disulfonates may reflect interpolation in an "intermediate lipid compartment" between the cytosolic drug and the site of drug action. PMID:8114079

  15. Association of glomerular filtration rate and inflammation with left ventricular hypertrophy in chronic kidney disease patients

    Dervisoglu, E; Kozdag, G; Etiler, N; Kalender, B

    2012-01-01

    Background: Although left ventricular hypertrophy (LVH) is an independent predictor of mortality in patients with end stage renal disease, few have examined its prevalence before the initiation of dialysis. The aim of this study was to investigate the relationship between LVH, estimated glomerular filtration rate (GFR), and inflammatory markers in patients with chronic kidney disease (CKD). Methods: Forty-one CKD patients (18 women, 23 men, mean age 5317 years) with an estimated GFR between 15 and 59 mL/min (mean 34.2 mL/min) were enrolled and the following tests performed: routine serum biochemical analyses, high sensitivity C-reactive protein (hs-CRP), fibrinogen, ferritin, and homocysteine, and left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS). Results: LVH was diagnosed in 32/41 patients (78%). CKD patients with LVH (n=32) had significantly higher hs-CRP (p=0.012), fibrinogen (p=0.031), and lower serum albumin (p=0.028) levels than those without LVH (n=9). In all patients, LVMI correlated positively with hs-CRP (r=0.483, p=0.002) and serum fibrinogen (r=0.426, p=0.015). Estimated GFR correlated positively with LVEF (r=0.414, p=0.007) and LVFS (r=0.376, p=0.018). Conclusions: Important positive associations exist between markers of inflammation and LVMI in patients with CKD. In addition to hs-CRP, elevated fibrinogen may portend the development of LVH in patients with CKD who are not yet on dialysis. PMID:23935269

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

    de Simone, G; Okin, P M; Gerdts, E; Olsen, M H; Wachtell, K; Hille, D A; Dahlöf, B; Kjeldsen, S E; Devereux, R B

    2009-01-01

    more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality......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 or...... 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...

  17. Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.

    Dellsperger, K C; Martins, J B; Clothier, J L; Marcus, M L

    1990-09-01

    Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size. PMID:1975521

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

    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for 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.

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

    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)

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

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

    1985-06-01

    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).

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

    Elena Ulasova

    2013-01-01

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

  2. Evaluation of right ventricular hypertrophy by thallium-201 myocardial perfusion image with vectorcadiography

    Right ventricular hypertrophy (RVH) was studied by Thallium-201 (201Tl) myocardial scintigraphy and vectorcardiography. The relationship between hypertrophy and volume or pressure overload was also examined in this way. Right ventricle (RV)/left ventricle (LV) Tl-201 uptake ratio and Q/P (rep. right ventricle diastolic dimension/left ventricle diastolic dimension) ratio on myocardial imaging of the left anterior oblique (LAO) view were measured in 37 patients with RVH in a hemodynamic study. The patients' QRS-loop Vectors in a horizontal plane were classified into four patterns (types I, II, III and IV) according to Chou's and Mori's classifications of RVH. The RV/LV uptake ratio and Q/P ratio were compared with four patterns of VCG. The relationship between those ratios and the pattern of VCG was clarified as a result of these studies. Types III and IV showed severe RVH patterns, with type III patients exhibiting a tendency of volume overload, while type IV patients tended foward pressure overload. Types I and II showed moderate RVH patterns. We concluded that more precise assessment of quantitative and qualitative analysis of RVH could be obtained by using 201Tl-RI myocardial scintigraphy in addition to VCG, elucidating the relationship between pressure and volume overloads which may affect the changes of VCG horizontal patterns. (author)

  3. 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

    2010-01-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca(2+) 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 Ca(2+) leak in the form of Ca(2+) quarks, increase the probability of occurrence of spontaneous Ca(2+) waves even with smaller SR Ca(2+) stores, accelerate Ca(2+) 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 Ca(2+) wave model under HF conditions provides a new view of Ca(2+) dynamics that could not be mimicked by adjusting traditional parameters involved in Ca(2+) release units and other ion channels, and contributes to understanding the underlying mechanism of HF. PMID:20505230

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

    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

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

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

  6. Does the ADMA/DDAH/NO pathway modulate early regression of left ventricular hypertrophy with esmolol?

    Quintana-Villamandos, Begoa; Delgado-Baeza, Emilio

    2016-02-01

    Hypertensive left ventricular hypertrophy (LVH) is a maladaptive response to chronic pressure overload and a strong independent risk factor for cardiovascular disease. Regression of LVH is associated with improved prognosis. Regression of LVH with antihypertensive therapy (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics) has been reported, although only after long-term treatment. Asymmetrical dimethylarginine (ADMA), the most potent endogenous NO synthase inhibitor, is emerging as an important cardiovascular risk factor in patients with arterial hypertension and LVH, and dimethylarginine dimethylaminohydrolase (DDAH) is the mechanism that most frequently leads to accumulation of ADMA (plasma ADMA is cleared in small part by renal excretion, although the bulk of ADMA is degraded by DDAH). Left ventricular mass is strongly modulated by the NO system. As an important inhibitor of the bioavailability of NO, ADMA is an underlying mechanism of LVH. Beta-blockers can induce regression of LVH and reduced plasma ADMA levels. Oxidative stress is increased in patients with LVH, and this in turn increases generation of ADMA. In a previous preclinical study of spontaneously hypertensive rats, we found that short-term treatment (48h) with esmolol reverses early LVH, increases the bioavailability of NO, and improves antioxidant status in plasma. Therefore, we propose that the ADMA/DDAH/NO pathway could modulate early regression of LVH with esmolol. PMID:26826640

  7. Organic Nitrates Favor Regression of Left Ventricular Hypertrophy in Hypertensive Patients on Chronic Peritoneal Dialysis

    Han Li

    2013-01-01

    Full Text Available The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH in hypertensive patients on chronic peritoneal dialysis (PD. Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two patients (nitrate group took isosorbide mononitrate for 24 weeks. The remaining 32 patients (non-nitrate group took other antihypertensive drugs. Blood pressure (BP, left ventricular mass index (LVMI and plasma asymmetric dimethylarginine (ADMA were monitored. Subjects with normal renal function were included as the control group (n = 30. At baseline, plasma ADMA levels in PD patients were significantly higher than the control group, but there was no significant difference in plasma ADMA levels between the two groups. At the end of the 24-week period, BP, LVMI, LVH prevalence and plasma ADMA levels in the nitrate group were significantly lower than those in the non-nitrate group. BP did not show a significant difference between 12 and 24 weeks in the nitrate group with a reduced need for other medication. Logistic regression analysis showed that nitrate supplementation and SBP reduction were independent risk factors of LVMI change in PD patients after adjusting for age, gender, diabetes history and CCB supplementation. It was concluded that organic nitrates favor regression of LVH in hypertensive patients on chronic peritoneal dialysis, and nitrates may be considered for use before employing the five other antihypertensive agents other than nitrates.

  8. Thyroid hormone induces cardiac myocyte hypertrophy in a TRα1-specific manner that requires TAK1 and p38 MAPK.

    Kinugawa, Koichiro; Jeong, Mark Y.; Bristow, Michael R.; Long, Carlin S.

    2005-01-01

    Alterations in thyroid hormone receptor (TR)1 isoform expression have been reported in models of both physiologic and pathologic cardiac hypertrophy as well as in patients with heart failure. In this report, we demonstrate that thyroid hormone (TH) induces hypertrophy as a direct result of binding to the TRα1 isoform and moreover, that over-expression of TRα1 alone is also associated with a hypertrophic phenotype, even in the absence of ligand. The mechanism of TH and TRα1-specific hypertroph...

  9. The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats.

    Elmedal, Britt; de Dam, Mette Y; Mulvany, Michael John; Simonsen, Ulf

    2004-01-01

    1. The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats. 2. Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not distal pulmonary arteries, from chronic hypoxic rats. 3. Treatment with tempol (86 mg x kg(-1) day(-1) in drinking water) normalized RVSP and reduced right ventricular hypertrophy, while systemic blood pressure, lung and liver weights, and blunted ACh relaxation of pulmonary arteries were unchanged. 4. Treatment with molsidomine (15 mg x kg(-1) day(-1) in drinking water) had the same effects as tempol, except that liver weight was reduced, and potassium and U46619-evoked vasoconstrictions in pulmonary arteries were increased. Combining tempol and molsidomine did not have additional effects compared to tempol alone. ACh relaxation in pulmonary arteries was not normalized by these treatments. 5. The media to lumen diameter ratio of the pulmonary arteries was greater for the hypoxic rats compared to the normoxic rats, and was not reversed by treatment with tempol, molsidomine, or the combination of tempol and molsidomine. 6. We conclude that tempol, like molsidomine, is able to correct RVSP and reduce right ventricular weight in the rat hypoxic model. Functional and structural properties of pulmonary small arteries were little affected. The results support the possibility that superoxide dismutase mimetics may be a useful means for the treatment of PH. PMID:14656807

  10. The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

    Elmedal, Britt; de Dam, Mette Y; Mulvany, Michael John; Simonsen, Ulf

    2003-01-01

    The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats.Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not distal pulmonary arteries, from chronic hypoxic rats.Treatment with tempol (86 mg kg−1 day−1 in drinking water) normalized RVSP and reduced right ventricular hypertrophy, while systemic blood pressure, lung and liver weights, and blunted ACh relaxation of pulmonary arteries were unchanged.Treatment with molsidomine (15 mg kg−1 day−1 in drinking water) had the same effects as tempol, except that liver weight was reduced, and potassium and U46619-evoked vasoconstrictions in pulmonary arteries were increased. Combining tempol and molsidomine did not have additional effects compared to tempol alone. ACh relaxation in pulmonary arteries was not normalized by these treatments.The media to lumen diameter ratio of the pulmonary arteries was greater for the hypoxic rats compared to the normoxic rats, and was not reversed by treatment with tempol, molsidomine, or the combination of tempol and molsidomine.We conclude that tempol, like molsidomine, is able to correct RVSP and reduce right ventricular weight in the rat hypoxic model. Functional and structural properties of pulmonary small arteries were little affected. The results support the possibility that superoxide dismutase mimetics may be a useful means for the treatment of PH. PMID:14656807

  11. Left ventricular hypertrophy and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe

    2002-01-01

    Background: This study investigated the association between electrocardiographically assessed left ventricular hypertrophy (LVH) and fatal, non-fatal, haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE.

  12. 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; Lambrechtsen, Jess; Sand, Niels Peter Rønnow; Nørgaard, Bjarne Linde; Mickley, Hans; Diederichsen, Axel Cosmus Pyndt

    2013-01-01

    PURPOSE:: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. In...... this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification. METHOD:: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A...... noncontrast computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage × QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association...

  13. Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy

    van der Merwe, Lize; Cloete, Ruben; Revera, Miriam; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; Brink, Paul A.; Moolman-Smook, Johanna C.

    2008-01-01

    Hypertrophic cardiomyopathy, a common, inherited cardiac muscle disease, is primarily caused by mutations in sarcomeric protein-encoding genes and is characterized by overgrowth of ventricular muscle that is highly variable in extent and location. This variability has been partially attributed to locus and allelic heterogeneity of the disease-causing gene, but other factors, including unknown genetic factors, also modulate the extent of hypertrophy that develops in response to the defective s...

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

    Cesare Cuspidi; Francesca Negri; Alberto Zanchetti

    2008-01-01

    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...

  15. LONG-TERM EFFECTS OF CHLORTHALIDONE VS HYDROCHLOROTHIAZIDE ON ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY IN THE MULTIPLE RISK FACTOR INTERVENTION TRIAL

    Ernst, Michael E; Neaton, James D.; Grimm, Richard H.; Collins, Gary; Thomas, William; Soliman, Elsayed Z.; Prineas, Ronald J

    2011-01-01

    Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy (LVH) is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial (MRFIT), which randomly assigned 8,012 hypertensive men to special intervention (SI) or usual care (UC). SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic use...

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

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

  17. Reverse mode of the sarcoplasmic reticulum calcium pump and load-dependent cytosolic calcium decline in voltage-clamped cardiac ventricular myocytes.

    Shannon, T R; Ginsburg, K S; Bers, D M

    2000-01-01

    We have characterized [Ca](i) decline in voltage-clamped rabbit ventricular myocytes with progressive increases in sarcoplasmic reticulum (SR) calcium load. "Backflux" through the SR calcium pump is a critical feature which allows realistically small values for SR calcium leak fluxes to be used. Total cytosolic calcium was calculated from the latter part of [Ca](i) decline using rate constants for cellular calcium buffers. Intra-SR calcium buffering characteristics were also deduced. We found...

  18. Allosteric Activation of Na+-Ca2+ Exchange by L-Type Ca2+ Current Augments the Trigger Flux for SR Ca2+ Release in Ventricular Myocytes

    Sobie, Eric A.; Cannell, Mark B; Bridge, John H.B.

    2008-01-01

    The possible contribution of Na+-Ca2+ exchange to the triggering of Ca2+ release from the sarcoplasmic reticulum in ventricular cells remains unresolved. To gain insight into this issue, we measured the “trigger flux” of Ca2+ crossing the cell membrane in rabbit ventricular myocytes with Ca2+ release disabled pharmacologically. Under conditions that promote Ca2+ entry via Na+-Ca2+ exchange, internal [Na+] (10 mM), and positive membrane potential, the Ca2+ trigger flux (measured using a fluore...

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

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

  20. 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)

    2014-08-29

    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 left ventricular myocytes.

  1. CAVEOLIN-3 IS UP-REGULATED IN THE PHYSIOLOGICAL LEFT VENTRICULAR HYPERTROPHY INDUCED BY VOLUNTARY EXERCISE TRAINING IN RATS

    Ikuo Yokoyama

    2002-12-01

    Full Text Available Various substances have been introduced in relation with cardiac hypertrophy almost always with controversy in their roles in signal transduction. Those controversies may attribute to the diversity of cardiac hypertrophy. We previously showed that calcineurin was activated in physiological left ventricular hypertrophy (LVH induced by voluntary exercise training, but not in decompensated pressure-overload LVH. In the current study, we advanced our search for the differences between the voluntary exercise-induced LVH and the pressure-overload LVH into several other hypertrophy-related substances including caveolin. Wistar rats were assigned to one of the following three groups: 10 weeks of voluntary exercise (EX, sedentary regimen (SED, and 4 weeks of ascending aortic constriction (AC. The EX rats voluntarily ran 1.6±1.1 km/day in the specially manufactured cages resulting in LVH (24 % increase in left ventricular weight per body weight ratio. Myocardial tissue homogenate of the EX rats revealed different characteristics in signal transduction of hypertrophy from that of the AC. The EX rats had normal sarcoplasmic reticulum (SR Ca2+ATPase mRNA level and normal myosin heavy chain isozyme pattern assessed by RNA protection assay, while AC rats had decreased SR Ca2+ATPase mRNA level and increased beta myosin heavy chain mRNA level. Myocardial caveolin-3 protein levels assessed by Western blotting increased in the EX rats but decreased in the AC rats. The voluntary exercise-induced LVH differed in signal transduction from the decompensated pressure-overload LVH. Caveolin-3 was induced in the voluntary exercise-induced LVH, while it was decreased in the decompensated pressure-overload LVH

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

    Aleksandra Zebrowska

    2009-03-01

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

  3. Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?

    Pol, Christine J; Muller, Alice; Simonides, Warner S

    2010-03-01

    Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established. PMID:19107595

  4. The three-dimensional arrangement of the myocytes aggregated together within the Mammalian ventricular myocardium

    Smerup, Morten; Nielsen, Eva Amalie; Agger, Peter; Frandsen, Jesper; Vestergaard-Poulsen, Peter; Andersen, Johnnie; Nyengaard, Jens; Pedersen, Michael; Ringgaard, Steffen; Hjortdal, Vibeke; Lunkenheimer, Paul P; Anderson, Robert H

    2009-01-01

    solitary tract of myocardial cells extending throughout the ventricular mass. Instead, each pathway possessed endocardial, midwall, and epicardial components, merging one into another in consistent fashion. Endocardial tracks, when followed towards the basal or apical parts of the left ventricle, changed...... similarly to endocardial tracks. This is the first study to show myocardial pathways that run through the mammalian left and right ventricles in a highly reproducible manner according to varying local helical and transmural intrusion angles. The patterns generated are an inherent feature of the three...

  5. Modulation by histamine of the delayed outward potassium current in guinea-pig ventricular myocytes.

    K. Yazawa; Abiko, Y.

    1993-01-01

    1. Histamine receptor-mediated modulation of the delayed outward potassium current (IK) was investigated in guinea-pig single ventricular cells by the whole-cell voltage clamp. 2. Histamine increased IK in a dose- dependent manner with a half-maximum dose of 3.8 x 10(-8) M. Histamine (10(-6) M) increased IK by a factor of 3.02 without a significant change in the current kinetics. The threshold dose of histamine for increasing IK was 10(-9) M and this value was similar to that for calcium curr...

  6. Screening for Fabry Disease by Urinary Globotriaosylceramide Isoforms Measurement in Patients with Left Ventricular Hypertrophy

    Gaggl, Martina; Lajic, Natalija; Heinze, Georg; Voigtländer, Till; Sunder-Plassmann, Raute; Paschke, Eduard; Fauler, Günter; Sunder-Plassmann, Gere; Mundigler, Gerald

    2016-01-01

    Background: Left ventricular hypertrophy (LVH) is a frequent echocardiographic feature in Fabry disease (FD) and in severe cases may be confused with hypertrophic cardiomyopathy (HCM) of other origin. The prevalence of FD in patients primarily diagnosed with HCM varies considerably in screening and case finding studies, respectively. In a significant proportion of patients, presenting with only mild or moderate LVH and unspecific clinical signs FD may remain undiagnosed. Urinary Gb3 isoforms have been shown to detect FD in both, women and men. We examined whether this non-invasive method would help to identify new FD cases in a non-selected cohort of patients with various degree of LVH. Methods and results: Consecutive patients older than 18 years with a diastolic interventricular septal wall thickness of ≥12mm determined by echocardiography were included. Referral diagnosis was documented and spot urine was collected. Gb3 was measured by mass spectroscopy. Subjects with an elevated Gb3-24:18 ratio were clinically examined for signs of FD, α-galactosidase-A activity in leukocytes was determined and GLA-mutation-analysis was performed. We examined 2596 patients. In 99 subjects urinary Gb3 isoforms excretion were elevated. In these patients no new cases of FD were identified by extended FD assessment. In two of three patients formerly diagnosed with FD Gb3-24:18 ratio was elevated and would have led to further diagnostic evaluation. Conclusion: Measurement of urinary Gb3 isoforms in a non-selected cohort with LVH was unable to identify new cases of FD. False positive results may be prevented by more restricted inclusion criteria and may improve diagnostic accuracy of this method.

  7. Tear me down: Role of calpain in the development of cardiac ventricular hypertrophy

    Patterson, Cam; Portbury, Andrea; Jonathan C. Schisler; Monte S Willis

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize...

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

    Bugenhagen, Scott M.; Beard, Daniel A.

    2015-10-01

    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 ?-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 ?-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) ?-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 CaMKII-mediated regulation of neither the LCC nor of PLB is required to explain the frequency-dependence of the data.

  9. THE PREVALENCE OF ARTERIAL HYPERTENSION AND THE SPECIFIC FEATURES OF DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY IN RADIATION-EXPOSED PERSONS

    S. K. Kukushkin

    2015-10-01

    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.

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

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

    2014-01-01

    Roč. 27, č. 1 (2014), s. 99-106. ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP301/10/0756; GA ČR(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant ostatní: Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.852, year: 2014

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

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

  12. 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)

    2012-02-17

    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.

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

    Yu-luan Xiang

    2012-03-01

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

  14. 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; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

    2012-03-01

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM. PMID:22331134

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

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

    2012-01-01

    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 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 inj...

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

    Cesare Cuspidi

    2008-03-01

    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

  17. 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.

    2000-01-01

    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.

  18. Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy

    Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients with hypertrophic hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed to determine the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was >12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7±3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked. (author)

  19. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

    Lowes, B D; Minobe, W; Abraham, W T; Rizeq, M N; Bohlmeyer, T J; Quaife, R. A.; Roden, R L; Dutcher, D L; Robertson, A.D.; Voelkel, N.F.; Badesch, D B; Groves, B M; Gilbert, E M; Bristow, M. R.

    1997-01-01

    Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation ...

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

    Luis R. Llerena Rojas

    2011-01-01

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

  1. Scintigraphic evaluation of ventricular hypertrophy using Tc-99m methoxyisobutyl isonitrile

    The usefulness of a newly developed myocardial imaging agent, Tc-99m methoxyisobutylisonitrile (MIBI), was assessed in 15 patients with hypertrophy. The patients underwent myocardial scintigraphy with Tc-99m MIBI at rest 30 minutes after the administration of 925 MBq. The findings were compared with those of concurrently performed myocardial scintigraphy with Tl-201 (111 MBq). Both types of scans showed hypertrophy in 14 patients. Of a total of 75 segments, 42 (56%) and 45 segmetns (61%) were found hypertrophied on Tc-99m MIBI and Tl-201 scans, respectively. In detecting hypertrophy, an overall concurrence rate between Tc-99m MIBI and Tl-201 scans was 50%: it tended to be high in the anterior and lateral segments and low in the apical, septal, and postero-inferior segments. Decrease or defect of uptake was more frequent on Tl-201 scans than on Tc-99m MIBI scans (9 vs 5 segments). When using echographically proven septum thickness, Tc-99m MIBI and Tl-201 scans defined the septum 13 mm or more and 11 mm or more as hypertrophy, respectively. For the septum 12 mm or more, the detection rates of Tc-99m MIBI and Tl-201 scans were 69% and 46%, respectively. On visual assessment, Tc-99m MIBI scans had the same diagnostic sensitivity as Tl-201 scans. In view of the potential of clear imaging and less overestimation, Tc-99m MIBI scans seemed to be useful in the diagnosis of hypertrophic heart. (N.K.)

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

    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 α-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.)

  3. 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)

    2011-07-15

    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.)

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

    Gerdts, E.; Cramariuc, D.; Simone, G. de; Wachtell, K.; Dahlof, B.; Devereux, R.B.

    2008-01-01

    AIMS: Less is known about the relation between in-treatment left ventricular (LV) geometry and risk of cardiovascular events. We assessed LV geometric patterns on baseline and annual echocardiograms as time-varying predictors of the primary composite endpoint (cardiovascular death, stroke, and...

  5. 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...

  6. 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; Oikarinen, Lasse; Nieminen, Markku S; Dahlöf, Björn; Devereux, Richard B

    2010-01-01

    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....

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

    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia Gry; Honge, Jesper L; Smerup, Morten Holdgaard; Hasenkam, J Michael; Sloth, Erik; Cremer, Signe Emilie; Olsen, Lisbeth H

    2014-01-01

    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...

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

    Boersma Hester

    2009-04-01

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

  9. Role of osteoprotegerin and its gene polymorphisms in the occurrence of left ventricular hypertrophy in essential hypertensive patients.

    Shen, Anna; Hou, Xuwei; Yang, Deguang; Liu, Tingrong; Zheng, Dezhong; Deng, Liehua; Zhou, Tao

    2014-12-01

    The aim of the study was to investigate the role of osteoprotegerin (OPG) in left ventricular hypertrophy (LVH) development in patients with essential hypertension (EH). A total of 1092 patients diagnosed with EH were recruited. The LVHs were determined and OPG gene polymorphisms were genotyped. Patients with LVH had a significantly higher mean serum OPG level than those without LVH. The 1181CC genotype carriers had significantly lower risk for LVH compared with GC and GG genotype carriers. The serum OPG level and OPG 1181 G>C polymorphism were found to be independent risk factors for the occurrence of LVH in hypertensive patients. In vitro study shows that OPG overexpression upregulates cell surface size, protein synthesis per cell, and hypertrophy- and fibrosis-related proteins in both cardiomyocytes and cardiac fibroblasts, whereas OPG inhibition can abolish the above-mentioned changes. Consistent with the in vitro data, our in vivo study revealed that the OPG administration induced the LVH in hypertensive rats. This study is the first to report the close association between OPG and LVH development in EH patients and the regulatory effect of OPG on cardiomyocytes and cardiac fibroblasts. PMID:25546658

  10. Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition after anterior Q-wave myocardial infarction.

    Jugdutt, B I; Humen, D P

    1998-05-01

    To determine whether limitation of left ventricular (LV) hypertrophy with angiotensin-converting enzyme inhibition after myocardial infarction (MI) is associated with improved systolic and diastolic function, quantitative two-dimensional echocardiograms and Doppler of 40 patients, who were randomized on day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and mass (3D reconstruction), remodeling parameters and peak early (E) and late (A) transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6 months and 1 year. Compared to placebo over 1 year, captopril limited (p ejection fraction and diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and hypertrophy and improved both systolic and diastolic function up to 1 year. PMID:9643276

  11. Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction

    Warren Stafford G

    2010-06-01

    Full Text Available Abstract Background Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD and left ventricular hypertrophy (LVH and low positive predictive value (PPV for prediction of left ventricular systolic dysfunction (LVSD. We hypothesized that a ~5-min resting 12-lead advanced ECG test ("A-ECG" that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. Results Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84% to 92% (88-96% (P Conclusion Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

  12. The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients.

    Erten, Yasemin; Ebinç, Fatma Ayerden; Ebinç, Haksun; Paşaoğlu, Hatice; Demirtaş, Canan; Taçoy, Gülten; Koç, Eyüp; Derici, Ulver; Reis, Kadriye Altok; Bali, Musa; Arinsoy, Turgay; Sindel, Sükrü

    2008-01-01

    Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-alpha, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-alpha levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 +/- 387.86 ng/mL) than hemodialysis (97.68 +/- 244.96 ng/mL,) and control (41.33 +/- 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-alpha (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = -0.305, p = 0.01), (r = -0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (beta = 0.369, p = 0.001) and IL-6 (beta = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-alpha. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index. PMID:18661412

  13. Hipertrofia ventricular esquerda em pacientes com doena renal crnica em tratamento conservador Left ventricular hypertrophy in patients with chronic kidney disease under conservative treatment

    Rachel Bregman

    2010-03-01

    Full Text Available A doena cardiovascular (DCV permanece sendo uma das maiores causas de morte em pacientes com doena renal crnica (DRC. A hipertrofia ventricular esquerda (HVE est presente em 75% dos pacientes ao iniciarem dilise, sugerindo que esta deve estar presente precocemente no curso da DRC. Poucos estudos avaliaram a prevalncia de HVE na pr-dilise. Foram avaliados 309 pacientes clinicamente estveis em acompanhamento por pelo menos trs meses em cinco Centros no Brasil. Perfil bioqumico e marcadores inflamatrios foram avaliados. Dados so 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 doena de base esteve presente em 35% dos pacientes em ambos os grupos. Filtrao glomerular estimada foi 30 11 e 32 12 mL/min para pacientes com HVE e sem, respectivamente (p = 0,19. A distribuio de pacientes mostrou que 60% com HVE se encontravam no estgio 4. Anlise logstica 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, respectively (p = 0.19. The distribution of patients showed that 60% of those with LVH were in stage 4. Multivariate logistic regression analysis indicated the following independent determinants for LVH: age (p < 0.001; calcium (p < 0.001; hemoglobin (p < 0.048; and diastolic blood pressure (p < 0.001. Systolic blood pressure, lipids, and inflammatory markers showed no correlation with LVH. In conclusion, the incidence of LVH was high even among patients under conservative treatment, and, except for age, LVH correlated with reversible factors. The need for strictly diagnosing CKD and preventing LVH in the predialysis phase is emphasized to decrease mortality due to CVD in that population.

  14. Pathologic ventricular hypertrophy in the offspring of diabetic mothers : a retrospective study

    Ullmo S.

    2007-01-01

    L'hypertrophie ventriculaire pathologique chez les nouveau-nés des mères diabétiques une étude rétrospective RESUME Objectif L'incidence du diabète chez les femmes enceintes ne cesse de croître, de même que les complications chez leurs nouveau-nés. C'est pourquoi, nous avons étudié la population de mères diabétiques suivies dans notre établissement entre les années 2003-2005 dans le but d'analyser spécifiquement le problème d'hypertrophie ventriculaire pathologique (HVP) chez les nouveau-nés ...

  15. 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)

    1992-03-01

    {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).

  16. Bilirubin Level is Associated with Left Ventricular Hypertrophy Independent of Blood Pressure in Previously Untreated Hypertensive Patients

    Ayaz, Teslime; Kocaman, Sinan Altan; Durako?lugil, Tu?ba; Erdo?an, Turan; ?ahin, Osman Zikrullah; ?ahin, Serap Baydur; iek, Yksel; ?atiro?lu, mer

    2014-01-01

    Background and Objectives Left ventricular hypertrophy (LVH), a sign of subclinical cardiovascular disease, is an important predictor of cardiovascular morbidity and mortality. The aim of our study was to determine the association of left ventricular mass (LVM) with possible causative anthropometric and biochemical parameters as well as carotid intima-media thickness (CIMT) and brachial flow-mediated dilation (FMD) as surrogates of atherosclerosis and endothelial dysfunction, respectively, in previously untreated hypertensive patients. Subjects and Methods Our study included 114 consecutive previously untreated hypertensive patients who underwent echocardiography and ultrasonography to evaluate their vascular status and function via brachial artery CIMT and FMD. Results Among all study parameters, age, systolic blood pressure (BP), diastolic BP, pulse pressure, plasma glucose, uric acid, total bilirubin, direct bilirubin, hemoglobin, and CIMT were positively correlated with the LVM index. Multiple logistic regression analysis revealed that office systolic BP, age, male gender, and total bilirubin were independent predictors of LVH. Conclusion Bilirubin seems to be related to LVM and LVH. The positive association of bilirubin with these parameters is novel and requires further research. PMID:25278987

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

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

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

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

    2002-12-01

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

  19. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

    Schunkert, H.; Dzau, V. J.; S. S. Tang; Hirsch, A. T.; Apstein, C S; Lorell, B. H.

    1990-01-01

    We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +...

  20. New Findings on the Effects of Tannic Acid: Inhibition of L-Type Calcium Channels, Calcium Transient and Contractility in Rat Ventricular Myocytes.

    Zhu, Fengli; Chu, Xi; Wang, Hua; Zhang, Xuan; Zhang, Yuanyuan; Liu, Zhenyi; Guo, Hui; Liu, Hongying; Liu, Yang; Chu, Li; Zhang, Jianping

    2016-03-01

    Tannic acid (TA) is a group of water-soluble polyphenolic compounds that occur mainly in plant-derived feeds, food grains and fruits. Many studies have explored its biomedical properties, such as anticancer, antibacterial, antimutagenic, antioxidant, antidiabetic, antiinflammatory and antihypertensive activities. However, the effects of TA on the L-type Ca(2+) current (ICa-L ) of cardiomyocytes remain undefined. The present study examined the effects of TA on ICa-L using the whole-cell patch-clamp technique and on intracellular Ca(2+) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge detection system. Exposure to TA resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half maximal inhibitory concentration of 1.69 μM and the maximal inhibitory effect of 46.15%. Moreover, TA significantly inhibited the amplitude of myocyte shortening and peak value of Ca(2+) transient and increased the time to 10% of the peak. These findings provide new experimental evidence for the cellular mechanism of action of TA and may help to expand clinical treatments for cardiovascular disease. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26762248

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

    George, Colleen; And Others

    1985-01-01

    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)

  2. Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in adult rabbit ventricular myocytes.

    Litwin, S E; J Li; Bridge, J H

    1998-01-01

    The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca release remains controversial. Therefore, we measured whole-cell Ca currents (ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na concentration markedly affected the relationship between cell shortening (or Ca transients) and voltage, but did not affect the Ca current-voltage relationship. We then inhibit...

  3. 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.

  4. The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

    Elmedal, Britt; de Dam, Mette Y; Mulvany, Michael John; Simonsen, Ulf

    2003-01-01

    The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats.Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN...

  5. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling

    Oka, Toru; Xu, Jian; Kaiser, Robert A.; Melendez, Jaime; Hambleton, Michael; Sargent, Michelle A.; Lorts, Angela; Brunskill, Eric W; Dorn, Gerald W., II; Conway, Simon J.; Aronow, Bruce J; Robbins, Jeffrey; Molkentin, Jeffery D

    2007-01-01

    The cardiac extracellular matrix is a dynamic structural support network that is both influenced by, and a regulator of, pathological remodeling and hypertrophic growth. In response to pathologic insults the adult heart re-expresses the secreted extracellular matrix protein periostin (Pn). Here we show that Pn is critically involved in regulating the cardiac hypertrophic response, interstitial fibrosis, and ventricular remodeling following long-term pressure overload stimulation and myocardia...

  6. 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

    2016-04-01

    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. PMID:26801307

  7. Usefulness of thallium-201 scintigraphy in predicting the development of angina pectoris in hypertensive patients with left ventricular hypertrophy

    Hypertension and left ventricular (LV) hypertrophy are independent risk factors for the development of coronary artery disease. To determine whether patients at higher risk for coronary artery disease can be identified, 40 asymptomatic hypertensive men with LV hypertrophy were prospectively studied using exercise thallium-201 scintigraphy and exercise radionuclide angiography. Endpoints indicative of coronary artery disease were defined as the subsequent development of typical angina pectoris, which occurred in 8 patients during a median follow-up of 38 months, or myocardial infarction, which did not occur. The exercise electrocardiogram was interpreted by standard ST-segment criteria and by a computerized treadmill exercise score. Abnormal ST-segment responses were present in 16 of the 40 hypertensives (40%), whereas the treadmill score was positive in 8 of those same 40 patients (20%). Scintigraphic perfusion defects assessed both visually and semiquantitatively were observed in 8 of 40 (20%) patients. An abnormal ejection fraction response to exercise was present in 40% (16 of 40) of patients, and 3 of 40 (7.5%) developed new wall motion abnormalities during exercise. Six of 8 patients with either perfusion defects or abnormal treadmill score developed typical angina during follow-up. All 5 patients with concordant positive exercise scintigrams and treadmill score developed chest pain during follow-up and had coronary artery disease confirmed by coronary angiography. However, only 7 of 16 (44%) patients with positive ST changes or abnormal ejection fraction responses during exercise developed chest pain during follow-up. In contrast, of 32 patients with negative scintigrams only 2 developed atypical chest pain syndromes, and significant coronary artery disease was excluded by angiography in 1 patient

  8. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study

    Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

    2016-01-01

    Objectives To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Design Case control study. Setti...

  9. Left ventricular outflow tract obstruction in the presence of asymmetric septal hypertrophy and accessory mitral valve tissue treated with alcohol septal ablation.

    Kim, Michael S; Klein, Andrew J; Groves, Bertron M; Quaife, Robert A; Salcedo, Ernesto E

    2008-09-01

    Redundant or accessory mitral valve tissue (AMVT) is a rare clinical condition. It is an even rarer cause of left ventricular outflow tract obstruction. We report a case of an adult male with medically unresponsive hypertrophic obstructive cardiomyopathy in whom real-time three-dimensional transesophageal echocardiography was used to both diagnose the presence of coexistent asymmetric septal hypertrophy and AMVT as well as confirm the safety and efficacy of treatment with alcohol septal ablation. PMID:18490281

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

    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 mm2) 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.)

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

    Assadi F ; Translated by: Akbari Asbagh P

    2007-04-01

    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.

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

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

  13. Electrocardiographic diagnosis of left ventricular hypertrophy in aortic valve disease: evaluation of ECG criteria by cardiovascular magnetic resonance

    Feuerbach Stefan

    2009-06-01

    Full Text Available Abstract Background Left ventricular hypertrophy (LVH is a hallmark of chronic pressure or volume overload of the left ventricle and is associated with risk of cardiovascular morbidity and mortality. The purpose was to evaluate different electrocardiographic criteria for LVH as determined by cardiovascular magnetic resonance (CMR. Additionally, the effects of concentric and eccentric LVH on depolarization and repolarization were assessed. Methods 120 patients with aortic valve disease and 30 healthy volunteers were analysed. As ECG criteria for LVH, we assessed the Sokolow-Lyon voltage/product, Gubner-Ungerleider voltage, Cornell voltage/product, Perugia-score and Romhilt-Estes score. Results All ECG criteria demonstrated a significant correlation with LV mass and chamber size. The highest predictive values were achieved by the Romhilt-Estes score 4 points with a sensitivity of 86% and specificity of 81%. There was no difference in all ECG criteria between concentric and eccentric LVH. However, the intrinsicoid deflection (V6 37 ± 1.0 ms vs. 43 ± 1.6 ms, p Conclusion By calibration with CMR, a wide range of predictive values was found for the various ECG criteria for LVH with the most favourable results for the Romhilt-Estes score. As electrocardiographic correlate for concentric LVH as compared with eccentric LVH, a shorter intrinsicoid deflection and a significant ST-segment and T-wave depression in the anterolateral leads was noted.

  14. TISSUE DOPPLER IMAGING OF LONGITUDINAL MOVEMENT OF A FIBROUS RING OF MITRAL VALVE DURING ISOVOLUMIC PERIODS IN LEFT VENTRICULAR HYPERTROPHY

    B. Amarjagal

    2015-12-01

    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 ?/?mm 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.

  15. Ischemic preconditioning effect of prodromal angina is attenuated in acute myocardial infarction patients with hypertensive left ventricular hypertrophy

    Several animal experiments on acute myocardial infarction (AMI) have shown that the cardioprotective effects of ischemic preconditioning are more significant in hypertensive subjects. However, because there are no clinical data on the impact of hypertension on ischemic preconditioning in patients with AMI, whether clinical ischemic preconditioning of prodromal angina was beneficial in AMI patients with hypertension was investigated in the present study. 125 patients with a first anterior AMI who had undergone successful reperfusion therapy were divided into 2 groups, with or without hypertension, and into 2 further subgroups based on the presence or absence of prodromal angina. Dual-isotope (thallium-201(TL)/Tc-99m pyrophosphate) single-photon emission computed tomography (SPECT) was performed within 1 week of reperfusion therapy. Left ventricular (LV) function and LV mass index (LVMI) were measured by left ventriculography and echocardiography, respectively. In patients without hypertension, prodromal angina resulted in significantly less myocardial damage on TL-SPECT, better LV ejection fraction and a greater myocardial blush grade compared to patients without prodromal angina. However, these cardioprotective effects of prodromal angina were significantly diminished in hypertensive patients. Importantly, the myocardial salvage effects of prodromal angina showed a significant negative correlation with LVMI, which was significantly greater in hypertensive patients. The cardioprotective effects of prodromal angina were attenuated in patients with hypertension. Hypertensive LV hypertrophy may crucially limit the effects of ischemic preconditioning in AMI. (author)

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

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

  17. EFFECT OF ANTIHYPERTENSIVE THERAPY BASED ON NEW METHOD OF INDIVIDUAL CHOICE OF DRUGS ON LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS

    K. I. Pshenichkin

    2015-12-01

    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.

  18. Differentiation between pathologic and physiologic left ventricular hypertrophy by tissue Doppler assessment of long-axis function in patients with hypertrophic cardiomyopathy or systemic hypertension and in athletes.

    Vinereanu, D; Florescu, N; Sculthorpe, N; Tweddel, A C; Stephens, M R; Fraser, A G

    2001-07-01

    To identify new echocardiographic indexes of long-axis function that might differentiate between pathologic and physiologic left ventricular (LV) hypertrophy, we compared 60 subjects with different types of LV hypertrophy (group I: 15 patients with hypertrophic cardiomyopathy, group II: 15 patients with systemic hypertension, and group III: 30 athletes) with 20 normal subjects (group IV). The peak velocities of mitral annular motion at 4 sites were measured from the apex by tissue Doppler echocardiography. There were no differences in mean age and global ejection fraction between groups. Groups I and II had lower long-axis systolic and early diastolic velocities than the athletes (p <0.01) for all 4 sites. The best differentiation of pathologic from physiologic hypertrophy was provided by a mean systolic annular velocity <9 cm/s (sensitivity 87%, specificity 97%). Heterogeneity of annular velocities discriminated between group I and group II. Thus, long-axis systolic and early diastolic velocities are decreased in patients with pathologic hypertrophy, but preserved in athletes. These simple new echocardiographic parameters can differentiate between pathologic and physiologic hypertrophy. PMID:11423058

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

    Vildbrad, Mads D; Andersen, Asger; Holmboe, Sarah; Ringgaard, Steffen; Nielsen, Jan M; Nielsen-Kudsk, Jens Erik

    2014-01-01

    surgery (n = 8), pulmonary trunk banding (PTB; n = 8), or monocrotaline injection (MCT; n = 7). RV function was evaluated at baseline and after injection of placebo and two concentrations of levosimendan (12 and 60 μg/kg) using magnetic resonance imaging, echocardiography, and invasive pressure recordings....... PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% ± 3.8% [P = 0.0038]; MCT: 9.9% ± 3.1% [P = 0.018]; PTB: 24.5% ± 3.3% [P = 0.0001]; mean ± SEM) compared with placebo....... Levosimendan markedly increased RV stroke volume (SV) in the MCT group (29.1% ± 8.3%; P = 0.012), did not change RV SV in the PTB group (0.4% ± 4.5%; P = 0.93), and decreased RV SV in the sham surgery group (-10.9% ± 3.7%; P = 0.020). Nitroprusside, which was used to mimic the systemic arterial vasodilator...

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

    Daniel, Piskorz; Alicia, Tommasi.

    2010-03-01

    Full Text Available Introduo. Em pacientes hipertensos considera-se que uma queda nos valores da presso arterial necessria para atingir a regresso da leso em rgos-alvo. O objetivo deste estudo determinar o efeito obtido com a diminuio da presso arterial em pacientes hipertensos arteriais na hipertrofia v [...] entricular esquerda em uma clnica especializada. Material e mtodos. Os pacientes hipertensos na primeira consulta, segundo definio da IV Guias da Federao Argentina de Cardiologia, com hipertrofia ventricular esquerda diagnosticada pelo mtodo ecocardiogrfico de Devereux, considerando sua presena com um ndice de massa ventricular esquerda igual ou superior a 110 g/m em mulheres e 125 g/m, em homens, divididos em dois grupos: 1) a presso arterial controlada: menos de 140 - 90 mm Hg ou inferior a 130 - 80 mm Hg em pacientes de alto risco, os pacientes com nefropatia diabtica ou portadores de doena isqumica do corao no final do seguimento, 2) presso arterial no controlada: acima dos valores estabelecidos no final do seguimento. Aplicou-se na anlise estadstica o teste t de Student, considerando-se significncia estatstica p Abstract in spanish Introduccin. En pacientes hipertensos se considera que el descenso de las cifras de presin arterial logra la regresin del dao en rgano blanco. El objetivo del presente estudio es determinar el efecto que se obtiene con el descenso de la presin arterial en pacientes hipertensos arteriales sobre [...] la hipertrofia ventricular izquierda en un consultorio especializado. Material y mtodos. Pacientes hipertensos en primera consulta segn definicin de las IV Guas de la Federacin Argentina de Cardiologa, con hipertrofia ventricular izquierda diagnosticada en ecocardiografa por mtodo de Devereux, considerndose su presencia con un ndice de masa ventricular izquierda mayor o igual a 110 gramos/m en las mujeres y 125 gramos/m en los hombres; divididos en dos grupos: 1) presin arterial controlada: menor a 140-90 mm Hg o menor a 130-80 mm Hg en pacientes de alto riesgo, diabticos, nefrpatas o portadores de cardiopata isqumica al final del seguimiento; 2) presin arterial no controlada: por encima de las cifras enunciadas al final del seguimiento. En el anlisis estadstico, se aplic test t de students, considerndose significacin estadstica p Abstract in english Background. In hypertensive patients it is considered that a fall in blood pressure values is necessary to achieve the regression of target organ damage. The aim of this study is to determine the effect obtained with decreasing blood pressure in hypertensive patients on left ventricular hypertrophy [...] in a specialized clinic. Methods. Hypertensive patients at first consultation as defined by Argentina Cardiology Federation Guides IV, with left ventricular hypertrophy diagnosed by echocardiographic method of Devereux, considering its presence with a left ventricular mass index equal or greater than 110 g/m in women and 125 g/m in men, divided into two groups: 1) controlled blood pressure: less than 140 - 90 mm Hg or lower than 130 - 80 mm Hg in high risk patients, patients with diabetic nephropathy or ischemic heart disease carriers at end of follow up, 2) uncontrolled blood pressure: above the values set out at the end of follow up. In statistical analysis t students test was applied, considering statistical significance p

  1. Calmodulin mutations associated with long QT syndrome prevent inactivation of cardiac L-type Ca(2+) currents and promote proarrhythmic behavior in ventricular myocytes.

    Limpitikul, Worawan B; Dick, Ivy E; Joshi-Mukherjee, Rosy; Overgaard, Michael T; George, Alfred L; Yue, David T

    2014-09-01

    Recent work has identified missense mutations in calmodulin (CaM) that are associated with severe early-onset long-QT syndrome (LQTS), leading to the proposition that altered CaM function may contribute to the molecular etiology of this subset of LQTS. To date, however, no experimental evidence has established these mutations as directly causative of LQTS substrates, nor have the molecular targets of CaM mutants been identified. Here, therefore, we test whether expression of CaM mutants in adult guinea-pig ventricular myocytes (aGPVM) induces action-potential prolongation, and whether affiliated alterations in the Ca(2+) regulation of L-type Ca(2+) channels (LTCC) might contribute to such prolongation. In particular, we first overexpressed CaM mutants in aGPVMs, and observed both increased action potential duration (APD) and heightened Ca(2+) transients. Next, we demonstrated that all LQTS CaM mutants have the potential to strongly suppress Ca(2+)/CaM-dependent inactivation (CDI) of LTCCs, whether channels were heterologously expressed in HEK293 cells, or present in native form within myocytes. This attenuation of CDI is predicted to promote action-potential prolongation and boost Ca(2+) influx. Finally, we demonstrated how a small fraction of LQTS CaM mutants (as in heterozygous patients) would nonetheless suffice to substantially diminish CDI, and derange electrical and Ca(2+) profiles. In all, these results highlight LTCCs as a molecular locus for understanding and treating CaM-related LQTS in this group of patients. PMID:24816216

  2. 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

    2016-04-15

    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. PMID:26892450

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

    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

  4. 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.

    1981-01-01

    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.

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

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

  6. Associations of Left Ventricular Hypertrophy with Prevalent and Incident Valve Calcification: The Multi-Ethnic Study of Atherosclerosis

    Elmariah, Sammy; Delaney, Joseph A. C.; Bluemke, David A; Budoff, Matthew J.; O’Brien, Kevin D.; Fuster, Valentin; Kronmal, Richard A.; Halperin, Jonathan L.

    2012-01-01

    Objectives We aim to evaluate the relationship between percent of predicted left ventricular mass (%PredLVM) and valve calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Background Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood. Methods MESA is a longitudinal cohort study of men and women aged 45-84 years without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling. Results Prevalent AVC was observed in 630 and MAC in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, gender, body mass index, ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (OR=1.18 per SD increase in %PredLVM [95%CI 1.08 – 1.30]; p=0.0004) and MAC (OR=1.18 [95%CI 1.06 – 1.32]; p=0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95%CI 0.15 – 0.38]; p<0.0001) and MAC (risk difference = 0.20 [95%CI 0.03 – 0.37]; p=0.02). During follow-up (mean 2.4±0.9 years), 153 subjects (4%) developed AVC and 198 (5%) MAC. %PredLVM was associated with incident AVC (OR=1.24 [95%CI 1.04 – 1.47]; p=0.02) and MAC (OR=1.18 [1.01-1.40]; p=0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification. Conclusions Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders. PMID:22897991

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

    Nabil Ghorayeb

    2005-09-01

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

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

    Bacchus R

    2011-07-01

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

  9. Tc-99m sestaMIBI SPECT imaging in angina patients with echocardiographic left ventricular hypertrophy (LVH)

    Left ventricular hypertrophy (LVH) is relatively common, occurring in 15-20% of the general population. LVH were known to exert an adverse influence on the accuracy of myocardial perfusion scintigraphy. However, most studies were done in the patients having hypertension. The diagnostic accuracy of the stress myocardial perfusion scan in the normotensive patients with LVH for the detection of significant coronary artery disease has not been separately examined. This study was prepared to determine the diagnostic accuracy of Tc-99m myocardial perfusion scan in patients with echocardiographic LVH. Tc-99m sestaMIBI myocardial scan was performed with either exercise (n=40) or adenosine (n=44) stress in 84 consecutive anginal patients with normal ECG. Fifty nine patients had significant coronary artery disease (>50%) in coronary angiogram. Overall sensitivity and specificity of the SPECT imaging were 88%, and 84% respectively. The patients were divided into two groups ; 1) LVH= patients with echocardiographic LVH(n=29) and 2) No LVH =patients without echocardiographic LVH(n=55). Sensitivities were 88% in both groups. Specificities were 67% in LVH and 100% in No LVH group ( p < 0.05). Fifty seven patients were normotensive and analyzed separately (LVH group =20, No LVH group = 37). Exercise stress was done in 29 and adenosine in 28 patients. Sensitivities and specificities were not significantly different in LVH and No LVH groups (83% vs 86%, p=NS and 88% vs 100%, p= NS) for the detection of coronary artery disease. Echocardiographic LVH does not appear to affect the diagnostic value of the Tc-99m sestaMIBI SPECT imaging in the normotensive angima patients

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

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

    2004-03-01

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

  11. [Effects of longevity-antihypertensive-mixture on essential hypertension and left ventricular hypertrophy].

    Wei, M; Chen, K J

    1990-10-01

    A study which enrolled 65 middle-aged and elderly essential hypertensive patients with Kidney-deficiency pattern was carried out to evaluate the effects of Longevity-Antihypertensive-Mixture (LAM). As LAM was composed of Kidney-tonifying herbs, all the subjects chosen fell into the pattern of Kidney-deficiency in TCM. The subjects were randomized into two groups: The LAM group had 34, and the control group taking Apocyhum Venetum L. Fluid (AVLF) 31. The duration of medication was 12 weeks. The main results were as follows: (1) At the end of week 4, the supine systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in LAM group declined from 171 +/- 16 (mmHg, the same below), 101 +/- 6 and 127 +/- 7 to 153 +/- 12, 93 +/- 7 and 113 +/- 7 respectively. At the end of week 12, the supine SBP, DBP and MBP were 151 +/- 14, 93 +/- 6 and 112 +/- 8. There was significance of difference in the reduction of supine blood pressure compared with baseline (P less than 0.001). AVLF produced similar changes in the reduction of supine SBP, DBP and MBP. However, the magnitude of reduction in SBP and MBP was smaller than those with LAM (P less than 0.001). (2) There was no significance of difference in attaining goal blood pressure between LAM and AVLF groups (P greater than 0.05). At the end of week 4, 79.41% and 77.42% were achieved respectively; at 12, 79.41% and 80.65%. (3) LAM had stronger effect on relieving symptoms of essential hypertension and Kidney-deficiency than AVLF (P less than 0.05). (4) In LAM group the left ventricular mass index (VMI) decreased from 114.75 +/- 42.40 g/m2 to 100.39 +/- 36.08 g/m2 (P less than 0.001). The LVMI in AVLF group increased from 117.27 +/- 36.90 g/m2 to 117.68 +/- 38.37 g/m2 (P greater than 0.05). The results supported the therapeutic principle of TCM: Treating patients according to their pathophysiological patterns. PMID:2148508

  12. 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: syh200415@yahoo.com.cn [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)

    2010-04-16

    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.

  13. Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte

    Michailova, A.; McCulloch, A.

    2001-01-01

    We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

  14. The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.

    Phan, Nam Nhut; Wang, Chih-Yang; Lin, Yen-Chang

    2014-10-01

    Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are arsenite (As(3+)) or arsenate (As(5+)). The mechanism of arsenic detoxification in humans still remains obscured. Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan is considered as high arsenic exposure country for long time ago. However, the effects of arsenic to cardiac functions still lacked of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, we found cardiac hypertrophy signaling may be the most significant pathway for up regulated genes in arsenic exposed patients via bioinformatics approach. To verify our bioinformatics prediction, arsenic was fed orally to rats at different concentration based on previous studies in Taiwan. Using hemodynamic method as the main tool to measure the changes in blood pressure, left ventricular pressure and left ventricular contractility index, the findings suggest that highly exposure to arsenic lead to hypertension; elevated left ventricular diastolic pressure and alteration in cardiac contractility which are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway. PMID:25089838

  15. Pathologic changes in the long-term transplanted heart: a morphometric study of myocardial hypertrophy, vascularity, and fibrosis.

    Rowan, R A; Billingham, M E

    1990-07-01

    Myocyte hypertrophy and myocardial fibrosis have been observed in transplanted human hearts, and both could potentially have an adverse effect on long-term cardiac function. There has been some concern that distant donor heart procurement and cyclosporine treatment increase the risk of these changes, but their incidence and severity have not been documented quantitatively in large numbers of cardiac transplant recipients. We used light microscopic morphometric methods to estimate myocardial collagen volume fraction and myocyte width in right ventricular endomyocardial biopsies from 95 recipients at 3 years posttransplantation, and electron microscopic stereology to estimate myocardial vascularity and myocyte myofibril content in 40 recipients, also at 3 years posttransplantation. We compared those with locally and distantly procured donor hearts (mean ischemic time 160 minutes) and cyclosporine versus noncyclosporine immunosuppression. Controls were pretransplant right ventricular biopsies from 20 donor hearts which were free of heart disease. We found no significant differences in myocardial collagen volume fractions. Myocyte hypertrophy was typical of all the transplant biopsies (mean myocyte width 20.2 microns, SD 3.0 in all transplants versus 11.8 microns, SD 2.2 in controls, P less than 0.001), but distant donor procurement and cyclosporine had no significant effect. There were significant reductions of myofibril volume fraction in the transplants, which raises the possibility of gradual decompensation in some patients. There were no significant differences in myocardial vascularity, although a few patients were well below the control range. We conclude that distant donor heart procurement, with ischemic times averaging less than 3 hours, and cyclosporine treatment are not responsible for significant hypertrophy or fibrosis in most transplants. Hypertrophy is typical of the transplanted heart, and it is possible that associated abnormalities might have an effect on cardiac function in some long-term survivors. PMID:2141825

  16. Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

    Hsu, Ting-Rong; Sung, Shih-Hsien; Chang, Fu-Pang; Yang, Chia-Feng; Liu, Hao-Chuan; Lin, Hsiang-Yu; Huang, Chun-Kai; Gao, He-Jin; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Lee, Pi-Chang; Yang, An-Hang; Chiang, Chuan-Chi; Lin, Ching-Yuang; Yu, Wen-Chung

    2014-01-01

    Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence of a cardiac Fabry mutation (IVS4 + 919G > A). The prevalence of this mutation is too high to be believed that it is a real pathogenic mutation. The purpose of this study is to identify the cardiac pathologic characteristics in patients with left ventricular hypertrophy and this mutation Methods and results Endomyocardial biopsies were obtained in 22 patients (Median age: 61, males: 17; females: 5) with lef...

  17. Myofibrillar Architecture in Engineered Cardiac Myocytes

    Parker, Kevin Kit; Tan, John; Chen, Christopher S.; Tung, Leslie

    2008-01-01

    Morphogenesis is often considered a function of transcriptional synchrony and the spatial limits of diffusing mitogens, however, physical constrainment by the cell microenvironment represents an additional mechanism for regulating self assembly of subcellular structures. We asked if myocyte shape is a distinct signal that potentiates the organization of myofibrillar arrays in cardiac muscle myocytes. We engineered the shape of neonatal rat ventricular myocytes by culturing them on microfabric...

  18. Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes

    Fan, Zhuo; Wen, Ting; Chen, Yaoxu; Huang, Lijie; Lin, Wei; Yin, Chunxia; Tan, Wen

    2016-01-01

    KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria. PMID:26949448

  19. α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

    NAKAYAMA, Hiroyuki; Bodi, Ilona; Correll, Robert N.; Chen, Xiongwen; Lorenz, John; Houser, Steven R; Robbins, Jeffrey; Schwartz, Arnold; Molkentin, Jeffery D

    2009-01-01

    In noncontractile cells, increases in intracellular Ca2+ concentration serve as a second messenger to signal proliferation, differentiation, metabolism, motility, and cell death. Many of these Ca2+-dependent regulatory processes operate in cardiomyocytes, although it remains unclear how Ca2+ serves as a second messenger given the high Ca2+ concentrations that control contraction. T-type Ca2+ channels are reexpressed in adult ventricular myocytes during pathologic hypertrophy, although their p...

  20. 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

    2015-01-01

    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 release. PMID:25609414

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

    Bassani R.A.

    2003-01-01

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

  2. MiR-139-3p is related to left ventricular hypertrophy and cardiomyocyte apoptosis in two-kidney one-clip hypertensive rats

    Yang Xiaomin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are important post-transcriptional regulators of gene expression in many physiological and pathological processes. Previous studies have reported the role of miR-139-3p in cancer. However, its specific roles and functions in the heart undergoing hypertrophy have yet to be fully elucidated. In the present study, a significant upregulation of miR-139-3p expression was demonstrated in the left ventricular myocardium of two-kidney one-clip (2K1C hypertensive rats using microarray and quantitative real-time PCR (qRT-PCR. Based on computational analysis, we observed that miR-139-3p can control the expression of mitogen-activated protein kinase 1 (MAPK1 as a target gene, which is essential for the induction of cardiac hypertrophy and cardiomyocyte apoptosis. This study provides first information that the highly expressed miR-139-3p might be closely involved in MAPK1-mediated cardiac hypertrophy and cardiomyocyte apoptotic processes in 2K1C rat.

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

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

    2012-07-01

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

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

    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 suppressed oxidative stress and the excess production of ROS. • Taxifolin blocked ERK1/2, JNK1/2 and Smad signaling pathways. • We reported that taxifolin had the potential to be a candidate for cardiac hypertrophy treatment

  5. 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: chen919085@163.com [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: wdwu55@163.com [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)

    2015-09-01

    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 suppressed oxidative stress and the excess production of ROS. • Taxifolin blocked ERK1/2, JNK1/2 and Smad signaling pathways. • We reported that taxifolin had the potential to be a candidate for cardiac hypertrophy treatment.

  6. 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.; Bella, J.N.; Aalto, T.; Dahlöf, B.; Gerdts, E.; Wright, J.T.; Papademetriou, V.; Mogensen, Carl Erik; Borch-Johnsen, Knut; Ibsen, H.; Devereux, R.B.

    2002-01-01

    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...

  7. Diagnstico electrocardiogrfico de la Hipertrofia Ventricular Izquierda en pacientes hipertensos. Utilidad del producto duracin por voltaje del QRS / Electrocardiography Diagnosis of the Left Ventricular Hypertrophy in hypertensive patients. Usefulness of the product of the duration of voltage of QRS

    Juan Lzaro, Gonzlez Moreno; Belkis, Martnez Martnez; Olga Mara, Rivero Gonzlez; Adys H, Salgado Friol; Pablo Jos, Daz San Jorge.

    2013-09-01

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

  8. Myocardial fibrosis and pathologic hypertrophy in the rat with renovascular hypertension.

    Weber, K T; Janicki, J S; Pick, R; Capasso, J; Anversa, P

    1990-04-01

    An abnormal elevation in collagen concentration or myocardial fibrosis occurs in the hypertrophied left ventricle of the rat with renovascular hypertension (RHT). The structural nature and functional consequences of this fibrosis and the mechanisms involved in its appearance were reviewed for various phases of hypertrophy. Within days after the onset of renal ischemia, type I collagen messenger ribonucleic acid is expressed. An interstitial fibrosis follows, characterized by an increased dimension of existing perimysial fibers and the appearance of fibrillar collagen in spaces previously devoid of collagen, together with a perivascular fibrosis of intramyocardial coronary arteries. These expressions of myocardial fibrosis are associated with an increase in diastolic and systolic myocardial stiffness. Endomyocardial fibrosis serves to further increase diastolic stiffness while myocytes encircled by fibrillar collagen become atrophic. Each of these consequences of myocardial fibrosis reduce myocyte length-dependent force generation. At 32 weeks of RHT there is an obvious diastolic and systolic dysfunction of the ventricle together with heart failure that includes ventricular dilatation, wall thinning and reduced ejection fraction. The mechanisms involved in mediating fibrosis in RHT appear to be multiple. Myocyte necrosis and fibroblast proliferation have been associated with elevated circulating angiotensin II. Necrosis in RHT was not seen with captopril pretreatment or in the hypertension and hypertrophy that accompanied infrarenal aorta banding. An alteration in coronary artery permeability may be responsible for the perivascular fibrosis that is not seen with captopril pretreatment. Thus in RHT, the hemodynamic status of the ventricle determines myocyte hypertrophy while the elevation in circulating angiotensin II is responsible for the remodeling of nonmyocyte compartments, including the appearance of myocardial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2138851

  9. Outcomes in atrial fibrillation patients with and without left ventricular hypertrophy when treated with a lenient rate-control or rhythm-control strategy.

    Badheka, Apurva O; Shah, Neeraj; Grover, Peeyush M; Patel, Nileshkumar J; Chothani, Ankit; Mehta, Kathan; Singh, Vikas; Deshmukh, Abhishek; Savani, Ghanshyambhai T; Rathod, Ankit; Panaich, Sidakpal S; Patel, Nilay; Arora, Shilpkumar; Bhalara, Vipulkumar; Coffey, James O; Mitrani, Raul D; Halperin, Jonathan L; Viles-Gonzalez, Juan F

    2014-04-01

    Although left ventricular (LV) hypertrophy has been proposed as a factor predisposing to atrial fibrillation (AF), its relevance to prognosis and selection of therapeutic strategies is unclear. We identified 2,105 patients with echocardiographic data on LV mass enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. LV hypertrophy was defined as increased LV mass, stratified by American Society of Echocardiography criteria. The primary end point was all-cause mortality, secondary end point was as per AFFIRM trial definition, and tertiary end point was cardiovascular hospitalizations. We compared "strict" versus "lenient" rate control in patients with increased LV mass, and studied association of heart failure (HF) with preserved and decreased systolic function in patients with increased LV mass. Over 6 years, 332 deaths (15.7%) were reported. Adjusted hazard ratio (HR) of severely increased LV mass for all-cause mortality was 1.34 (95% confidence interval [CI] 1.01 to 1.79, p=0.045) for the overall population and 1.61 (95% CI 1.09 to 2.37, p=0.016) for the rhythm-control arm. Increased LV mass was a predictor of cardiovascular hospitalizations in the lenient rate-control group (HR 1.72, 95% CI 1.05 to 2.82, p=0.03) but not in the strict rate-control group. Severely increased LV mass was predictive of cardiovascular hospitalizations in patients with HF with preserved (HR 1.8, 95% CI 1.0 to 3.2, p=0.03) and decreased LV systolic function (HR 2.4, 95% CI 1.1 to 5.2, p=0.02). Thus, LV hypertrophy is a significant independent predictor of mortality in patients with AF, especially those managed with rhythm control. In patients with LV hypertrophy, strict rate control may be associated with better outcomes than lenient rate control. LV hypertrophy portends higher cardiovascular morbidity in patients with AF and HF. PMID:24507168

  10. 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

    2010-08-01

    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, however, since it does not appear to exist among diabetic AMI survivors.

  11. 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: cxy0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Shihua, E-mail: zhaoshihua0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Tao, E-mail: taozhao0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Lu, Minjie, E-mail: lmjkan@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Yin, Gang, E-mail: gangyin0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jiang, Shiliang, E-mail: jiangsl-2011@163.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Prasad, Sanjay, E-mail: s.prasad@rbht.nhs.uk [NIHR Biomedical Research Unit, Royal Brompton Hospital Sydney Street, London, SW3 6NP (United Kingdom)

    2014-02-15

    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.

  12. Cardiotrofina-1 circulante puede diferenciar la hipertrofia ventricular fisiológica del atleta de la hipertrofia patológica del paciente hipertenso Circulating cardiotrophyn-1 may help differenciate left ventricular hypertrophy seen in athletes from pathologic left ventricular hypertrophy associated to hypertension

    Luigi Gabrielli

    2009-04-01

    Full Text Available Introducción: Cardiotrofina-1 (CT-1, una citoquina perteneciente a la superfamilia de la interleukina-6, se encuentra elevada en pacientes con hipertensión arterial (HTA e hipertrofia ventricular izquierda (HVI. Sus niveles se correlacionan con el tamaño auricular izquierdo y con las presiones de llenado del ventrículo izquierdo. Los niveles de CT-1 en atletas con HVI fisiológica no han sido investigados. Métodos: Estudio transversal. Se incluyeron pacientes con HTA esencial con y sin evidencia ecográfica de cardiopatía hipertensiva (CH(HVI y relación E/E'>10, recientemente diagnosticada y sin tratamiento. Un grupo de atletas normotensos con diagnóstico ecográfico de HVI y un grupo control de sujetos normotensos pareados por edad y sexo. En todos los sujetos se midieron los niveles plasmáticos de CT-1 (ELISA. Se definió HVI mediante diagnóstico ecocargiográfico, utilizando el índice de masa ventricular izquierda usando la fórmula de Devereux (hombres ³115 gramos/m², mujer ³95 gramos/m². Las presiones de llenado del VI se estimaron con la relación E/E' (doppler tisular en el anillo mitral medial. Resultados: Se incluyeron 10 pacientes por grupo. Los atletas con HVI presentaron una relación E/E' Background: Cardiotrophyn-1 (CT-1, is a cytokine which is increased in patients with hypertension (HT and left ventricular hypertrophy (LVH. This increase occurs in proportion to left atrial size and left ventricular filling pressures. CT-1 levels in athletes with LVH have not been investigated Methods: Crossectional study. We evaluated: a hypertensive patients with LVH and E/E' > 10 by echocardiography, recently diagnosed and receiving no medications; b normotensive athletes with LVH as shown by echocardiography, and c normotensive subjects, paired by age and sex. Plasma levels of CT-1 (ELISA were measured in all. LVH was defined as left ventricular mass index > 115 G/m² (males or > 95 G/m² (females. Results: E/E' was lower in athletes than hypertensive patients with LVH (6.5 ± 1 vs 12.9 ± 1.1, p<0.01. E/E' in both control subjects and patients with HTA but no LVH did not differ from E/E' in athletes. CT-1 was lower in athletes than patients with HTA and LVH (6.6 ± 0.4 vs 18.2 ± 5.6 fmol/ml, respectively, p<0.001. CT-1 levels in control subjects and hypertensive patients without LVH did not differ from that found in athletes. Conclusion: CT-1 levels are similar in athletes compared to normal subjects and patients with HTA and no LVH. Hypertensive patients with similar grades of LVH and left ventricular diastolic dysfunction had significantly greater leves of CT-1. Thus, CT-1 levels could help differentiate pathological HVI from physiologic LVH in athletes.

  13. Determinants of Left Ventricular Hypertrophy in Hypertensive Patients: Identification of High-Risk Patients by Metabolic, Vascular, and Inflammatory Risk Factors

    Peer, Maya; Boaz, Mona; Zipora, Matas; Shargorodsky, Marina

    2013-01-01

    Left ventricular hypertrophy (LVH) is recognized as an independent predictor of cardiovascular morbidity and mortality in hypertensive patients. Thus, it is critical to understand the mechanisms underlying the development of LVH for formulation screening and treatment strategies. This study was designed to determine the association between echographically determined LVH measures and markers of inflammation, neurohormonal activity, glomerular function, oxidative stress, insulin resistance, and vascular endothelial function. In this study, 129 hypertensive subjects were evaluated for lipids, glucose, HbA1C, insulin, homeostasis model assessment-insulin resistance, C-reactive protein (CRP), urinary microalbumin, homocysteine, aldosterone, renin, and endothelin. LVH parameters including interventricular septum thickness, posterior wall thickness (PWT), and left ventricular mass index (LVMI) were assessed echographically. Serum aldosterone levels were significantly positively associated with left ventricular mass (LVM) and marginally positively associated with LVMI and PWT. Both LVM and LVMI were significantly elevated in subjects with high versus normal serum aldosterone levels (p?=?0.018 for LVM and p?=?0.050 for LVMI). Serum endothelin was positively associated with LVM and LVMI. In multiple linear regression analysis, aldosterone remained a significant predictor of LVM (standardized ??=?0.229, p?=?0.024), and endothelin a marginally significant predictor of LVM (standardized ??=?0.178, p?=?0.077). Among serum lipids, high-density lipoprotein cholesterol only had a significant inverse association with LVM and PWT. Homocysteine as well as CRP were significantly positively associated with LVM and LVMI in females. This study found that aldosterone and endothelin levels are the most important independent determinants of LVH in hypertensive subjects. These markers may be useful to identify asymptomatic hypertensive subjects at risk for heart failure. PMID:24436616

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

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

    2014-01-01

    Roč. 2014, č. 2014 (2014), s. 920208. ISSN 2314-6133 Grant ostatní: GA MZd NT14301 Institutional support: RVO:61388998 Keywords : calcium efflux * calcium buffers * cardiac myocyte * computer model Subject RIV: BO - Biophysics Impact factor: 1.579, year: 2014

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

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

    2012-01-01

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

  16. Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice / Prpolis e natao na preveno da aterognese e hipertrofia ventricular esquerda de camundongos hipercolesterolmicos

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

    2015-05-01

    Full Text Available Objetivos O presente estudo verificou o efeito do prpolis associao ou no com a natao na dislipidemia, na hipertrofia ventricular esquerda e aterognese de camundongos hipercolesterolmicos. Mtodos e Resultados Os experimentos foram realizados em camundongos LDLr/, alimentados com dieta hip [...] erlipdica por 75 dias, e divididos em quatro grupos experimentais (n = 10): HL, sedentrios, foram submetidos ao estresse aqutico (5 min por dia, cinco vezes por semana); NAT foram submetidos a um protocolo de natao (1 hora por dia, cinco vezes por semana) a partir do 16 dia do experimento; PRO, sedentrios, submetidos a estresse aqutico e que receberam extrato de prpolis oral (70 uL / animal / dia) a partir do 16 dia do experimento; HL + NAC + PRO, submetidos a natao e que recebeu a prpolis, como descrito acima. Aps 75 dias, foi coletado sangue para anlise do perfil lipdico. Calculou-se a relao entre o peso ventricular (mg) e o peso do animal (g). Os cortes histolgicos do corao e aorta foram processados imunohistoqumicamente com anticorpos anti-CD40L para avaliar o processo inflamatrio, corados com hematoxilina / eosina e picrossrius red, para avaliar as alteraes morfolgicas e morfomtricas. Os camundongos HL apresentaram dislipidemia grave, aterognese e hipertrofia do ventrculo esquerdo, associada a uma diminuio dos nveis plasmticos de HDLc e o desenvolvimento subsequente do processo inflamatrio cardiovasculares, caracterizada pelo aumento da expresso do CD40L no ventrculo esquerdo e na aorta. Natao e a prpolis isolado e \\ ou associados preveniram a HVE, a aterognese e a inflamao tanto na artria quanto no ventrculo, diminuindo a expresso de CD40L, aumentando os nveis plasmticos de HDLc. Concluso A Prpolis isolada ou associada a uma atividade fsica regular benfica na proteo cardiovascular atravs da ao anti-inflamatria. Abstract in english Aims The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. Methods and Results The experiments were performed in LDLr/ mice, fed with high fat diet for 75 days, and we [...] re divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and\\or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. Conclusion Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action.

  17. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    Trimarchi Francesco

    2006-02-01

    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.

  18. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a casecontrol study

    Bahramali, Ehsan; Rajabi, Mona; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

    2016-01-01

    Objectives To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Design Case control study. Setting An Iranian referral university hospital. Participants 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. Results The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. Conclusions In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. PMID:26861937

  19. 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

    2016-01-01

    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. PMID:26739528

  20. Yin Yang 1 represses alpha-myosin heavy chain gene expression in pathologic cardiac hypertrophy.

    Mariner, Peter D; Luckey, Stephen W; Long, Carlin S; Sucharov, Carmen C; Leinwand, Leslie A

    2005-01-01

    In the work presented here, we elucidate a mechanism for the repression of alpha-myosin heavy chain (MyHC) during pathological cardiac hypertrophy. We demonstrate that the transcription factor Yin Yang 1 (YY1) significantly decreases endogenous alpha-MyHC mRNA and protein expression in neonatal rat ventricular myocytes. Furthermore, mutation of the YY1 binding sites in the proximal rat alpha-MyHC promoter increases promoter activity and alleviates YY1-mediated repression of the promoter. Despite the presence of 5 sites that bind YY1, only one site, located at -94bp of the rat alpha-MyHC promoter, is both necessary and sufficient for pathological repression of the promoter by phorbol esters, revealing a unique mechanism for the repression of alpha-MyHC expression during cardiac hypertrophy. PMID:15567155

  1. [Cardiomyopathy showing progression from diffuse left ventricular hypertrophy to dilated phase associated with mitochondrial DNA point mutation A3243G: A case report].

    Ohmoto, Naoki; Fujiwara, Yoshimasa; Kibira, Satoshi; Kobayashi, Masao; Saito, Takashi; Miura, Mamoru

    2003-01-01

    A 44-year-old man was admitted to our hospital because of congestive heart failure. He had various symptoms caused by insulin-dependent diabetes mellitus, sensorineural deafness, Wolff-Parkinson-White syndrome and cardiomyopathy associated with mitochondrial DNA point mutation A3243G. Echocardiography had showed symmetrical hypertrophy of the left ventricular wall and normal cardiac function (ejection fraction 55%) at age 32 years. However, echocardiography showed cardiac transformation, consisting of posterior wall thinning and significantly reduced cardiac function (ejection fraction 11%), at age 44 years. Electrocardiography showed lowered R-wave in the chest leads and QRS widening. Both lactic acid and pyruvate serum levels were increased. Mitochondrial respiratory enzyme analysis in gastrocnemius muscle tissue indicated a partial deficiency of rotenone-sensitive NADH cytochrome C reductase. He was discharged from our hospital, and medically treated with coenzyme Q10(30 mg/day). He had no progression of cardiomyopathy or congestive heart failure. However, he suddenly died of lactic acidosis at age 47 years. PMID:12564110

  2. 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

    2009-04-01

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

  3. Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

    Peters, Christian D.; Schou, Uffe K.; Jensen, Jens L.; Magnusson, Nils E.; Ørntoft, Torben F.; Kruhøffer, Mogens; Simonsen, Ulf

    2011-01-01

    Background The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. Methodology/Principal Findings To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. Conclusion/Significance Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure. PMID:21246034

  4. 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

    2011-09-01

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

  5. 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

    2012-01-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esquerda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguidos até outubro de 2010. Foram traçadas curvas de sobrevida comparando a mortalidade cardiovascular, e por todas as causas dos pacientes com escolaridade de até três anos (mediana da escolaridade e pacientes com escolaridade igual ou superior a quatro anos. Foram construídos modelos múltiplos de Cox ajustados para as variáveis de confusão. RESULTADOS: Observou-se associação entre nível de escolaridade e hipertrofia ventricular. A diferença estatística de mortalidade de origem cardiovascular e por todas as causas entre os diferentes níveis de escolaridade ocorreu aos cinco anos e meio de seguimento. No modelo de Cox, a hipertrofia ventricular e a proteína-C reativa associaram-se à mortalidade por todas as causas e de origem cardiovascular. A etiologia da insuficiência renal associou-se à mortalidade por todas as causas e a creatinina associou-se à mortalidade de origem cardiovascular. A associação entre escolaridade e mortalidade perdeu significância estatística no modelo ajustado. CONCLUSÃO: Os resultados do presente trabalho confirmam estudo prévio e demonstram, ademais, que a maior mortalidade cardiovascular observada nos pacientes com menor escolaridade pôde ser explicada por fatores de risco de ordem bioquímica e de morfologia cardíaca.FUNDAMENTO: La hipertrofia ventricular izquierda es potente predictor de mortalidad en renales crónicos. Estudio previo de nuestro grupo mostró que renales crónicos con menor escolaridad tienen hipertrofia ventricular más intensa. OBJETIVO: Ampliar estudio previo y verificar si la hipertrofia ventricular izquierda puede justificar la asociación entre escolaridad y mortalidad cardiovascular de pacientes en hemodiálisis. MÉTODOS: Fueron evaluados 113 pacientes entre enero de 2005 y marzo de 2008 y seguidos hasta octubre de 2010. Fueron trazadas curvas de sobrevida comparando la mortalidad cardiovascular, y por todas las causas de los pacientes con escolaridad de hasta tres años (mediana de la escolaridad y pacientes con escolaridad igual o superior a cuatro años. Fueron construidos modelos múltiples de Cox ajustados para las variables de confusión. RESULTADOS: Se observó asociación entre nivel de escolaridad e hipertrofia ventricular. La diferencia estadística de mortalidad de origen cardiovascular y por todas las causas entre los diferentes niveles de escolaridad ocurrió a los cinco años y medio de seguimiento. En el modelo de Cox, la hipertrofia ventricular y la proteína-C reactiva se asociaron a la mortalidad por todas las causas y de origen cardiovascular. La etiología de la insuficiencia renal se asoció a la mortalidad por todas las causas y la creatinina se asoció a la mortalidad de origen cardiovascular. La asociación entre escolaridad y mortalidad perdió significación estadística en el modelo ajustado. CONCLUSÓN: Los resultados del presente trabajo confirman estudio previo y demuestran, además, que la mayor mortalidad cardiovascular observada en los pacientes con menor escolaridad puede ser explicada por factores de riesgo de orden bioquímico y de morfología cardíaca.BACKGROUND: Left ventricular hypertrophy is a strong predictor of mortality in chronic kidney patients. A previous study of our group has shown that chronic kidney patients with low educational level has more severe ventricular hypertrophy. OBJECTIVE: To extend a previous study and to assess whether left ventricular hypertrophy can explain the association between schooling and cardiovascular mortality in hemodialysis patients. METHODS: This study assessed 113 patients from January 2005 to March 2008 and followed them up until October 2010. Survival curves were built to compare all-cause and cardiovascular mortality of patients with up to three years of schooling (median schooling and those with schooling of four years and over. Cox multiple models were built and adjusted to confounding variables. RESULTS: Association between educational level and ventricular hypertrophy was observed. Statistical difference in all-cause and cardiovascular mortality between the different educational levels was observed at 5.5 years of follow-up. In the Cox model, ventricular hypertrophy and C-reactive protein associated with all-cause and cardiovascular mortality. The etiology of kidney failure associated with all-cause mortality, and creatinine associated with cardiovascular mortality. The association between educational level and mortality lost statistical significance in the adjusted model. CONCLUSION: The results of this study confirm those of a previous study. In addition, they show that the higher cardiovascular mortality observed in patients with low educational level can be explained by risk factors of biochemical and cardiac morphological origin.

  6. Alteraes morfolgicas e funcionais cardacas e anlise dos fatores determinantes de hipertrofia ventricular esquerda em 40 pacientes com acromegalia Cardiac morphology and performance alterations and analysis of determinant factors of left ventricular hypertrophy in 40 patients with acromegaly

    Alessandra Ferri Casini

    2006-02-01

    Full Text Available A acromegalia uma doena de alta mortalidade, especialmente em razo de complicaes cardiovasculares. Com o objetivo de avaliar os fatores determinantes da hipertrofia ventricular esquerda (HVE e as alteraes cardacas na acromegalia, analisamos 40 acromeglicos submetidos a exames clnico-laboratoriais e ao ecocardiograma. As variveis analisadas foram idade, sexo, durao de doena, hipertenso arterial (HA, intolerncia glicose/DM, uso ou no de octreotide, GH e %IGF-I. Na anlise univariada, pacientes com HVE foram mais idosos (p= 0,031, apresentaram maior prevalncia de HA (p= 0,009 e maiores valores da %IGF-I (p= 0,002, comparados aos sem HVE. Na anlise multivariada, HA e %IGF-I foram determinantes de HVE (p= 0,035 e p= 0,016. Aps a dicotomizao da %IGF-I, foi criado um escore e a freqncia de HVE foi 9%, 65%, 92% x 0, 1, 2; pAcromegaly has a high mortality rate due mainly to cardiovascular complications. The aim was to evaluate the determinant factors of left ventricular hypertrophy (LVH and cardiac alterations in 40 acromegalic patients submitted to clinical-laboratorial studies and echocardiogram. The variables analyzed were age, sex, disease duration, arterial hypertension (AH, impaired glucose tolerance/DM, previous treatment with octreotide, GH and %IGF-I. Univaried analysis showed that patients with LVH were older (p= 0.031, had higher prevalence of AH (p= 0.009 and higher %IGF-I (p= 0.002, than those without LVH. Multivaried analysis showed AH and %IGF-I as determinants of LVH (p= 0.035 and p= 0.016. After dichotomizing of %IGF-I, a score was created and the frequency of LVH was 9%, 65%, 92% x 0, 1, 2; p< 0.0001. Prevalence of aortic ectasia was higher and valvar disease was smaller than reported in the literature. We conclude that AH and %IGF-I were determinants of LVH.

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

    Olsen, M H; Christensen, M K; Wachtell, K; Tuxen, Christian; Fossum, E; Bang, L E; Wiinberg, N; Devereux, R B; Kjeldsen, S E; Hildebrandt, Per; Dige-Petersen, H; Rokkedal, J; Ibsen, H

    2005-01-01

    Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy...

  8. Papel del estrés oxidativo y nitrosativo en la hipertrofia cardiaca y remodelación ventricular Role of oxidative and nitrosative stress in cardiac hypertrophy and ventricular remodeling

    Alejandro Giraldo

    2010-06-01

    Full Text Available Objetivo: hacer una revisión de los mecanismos moleculares del estrés oxidativo y nitrosativo en la fisiopatología de la falla cardiaca. Metodología: se hizo una búsqueda en Medline (Pubmed con las palabras clave: oxidative stress, ventricular remodeling, heart failure y nitrosative stress. Se consultó además bibliografía citada por autores de reconocida trayectoria en investigación en este tema. Resultados: se seleccionaron los 112 artículos más relevantes en el tema de estrés oxidativo/ nitrosativo que se relacionarán con falla cardiaca. Conclusiones: las respuestas de estrés de los cardiomiocitos y del tejido miocárdico es muy probable que constituyan un aspecto significativo del desarrollo de patologías cardiacas que desencadenan como evento final su progresión hacia falla cardiaca. El estrés oxidativo es un tema común en la fisiopatología de la cardiomiopatía isquémica y no isquémica. Patologías cardiacas como la falla cardiaca son usualmente precedidas de hipertrofia cardiaca secundaria, al menos en parte, a la generación de especies reactivas del oxígeno en los cardiomiocitos. Varios son los mecanismos implicados en la remodelación ventricular y progresión de la falla cardiaca que dependen de alteraciones homeostáticas en los sistemas que generan estrés oxidativo y/o nitrosativo. La discusión se centra en la reciente evidencia derivada de investigaciones llevadas a cabo tanto in vitro en cardiomiocitos cultivados como in vivo en modelos experimentales de patologías cardiacas. Las implicaciones clínicas de los recientes descubrimientos aunque son muy prometedoras para la terapéutica de la falla cardiaca, aun no han logrado trasladarse con total éxito a la práctica clínica en los ensayos clínicos realizados hasta el momento (Acta Med Colomb 2010; 2010; 35: 82-95.Objective: to review the molecular mechanisms of oxidative and nitrosative stress in the process of ventricular remodeling and the pathophysiology of heart failure. Metodology: a Medline (PubMed search was performed using the keywords: oxidative stress, ventricular remodeling, heart failure, nitrosative stress. Cited bibliography in key papers from renowned authors in this field of research was also examined. Results: 112 articles were selected as the most relevant regarding the several systems of oxidative stress production in the cardiovascular system in addition to their relevance to the pathophysiology of heart failure. Conclusions: the stress responses of cardiomyocytes and the myocardial tissue as a whole are likely to constitute a significant aspect of the development of cardiac pathologies. Oxidative stress is a common theme in the pathophysiology of ischemic and non-ischemic cardiomyopathy. Cardiac pathologies such as heart failure are usually preceded by cardiac hypertrophy secondary, at least in part, to the generation of reactive oxygen species in cardiomyocytes. Several mechanisms have been implicated in ventricular remodeling during heart failure progression which depends on homeostatic alterations in oxidative and nitrosative stress. The discussion is centered in the exposition of recent evidence from research carried out either in vitro in cultured cardiomyocytes as well as from in vivo models of experimental cardiac pathologies. The clinical implications of this novel understanding, although very promising for the therapeutic treatment of heart failure, up until now, have failed to translate with total success to the clinical practice in several clinical trials (Acta Med Colomb 2010; 2010; 35: 82-95.

  9. Delayed hyperenhancement in magnetic resonance imaging of left ventricular hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy: visualisation of focal fibrosis

    Debl, K; Djavidani, B; Buchner, S; Lipke, C; Nitz, W; Feuerbach, S; Riegger, G; Luchner, A

    2006-01-01

    Objective To compare the extent and distribution of focal fibrosis by gadolinium contrast‐enhanced magnetic resonance imaging (MRI; delayed hyperenhancement) in severe left ventricular (LV) hypertrophy in patients with pressure overload caused by aortic stenosis (AS) and with genetically determined hypertrophic cardiomyopathy (HCM). Methods 44 patients with symptomatic valvular AS (n  =  22) and HCM (n  =  22) were studied. Cine images were acquired with fast imaging with steady‐state precession (trueFISP) on a 1.5 T scanner (Sonata, Siemens Medical Solutions). Gadolinium contrast‐enhanced MRI was performed with a segmented inversion–recovery sequence. The location, extent and enhancement pattern of hyperenhanced myocardium was analysed in a 12‐segment model. Results Mean LV mass was 238.6 (SD 75.3) g in AS and 205.4 (SD 80.5) g in HCM (p  =  0.17). Hyperenhancement was observed in 27% of patients with AS and in 73% of patients with HCM (p < 0.01). In AS, hyperenhancement was observed in 60% of patients with a maximum diastolic wall thickness ⩾ 18 mm, whereas no patient with a maximum diastolic wall thickness < 18 mm had hyperenhancement (p < 0.05). Patients with hyperenhancement had more severe AS than patients without hyperenhancement (aortic valve area 0.80 (0.09) cm2v 0.99 (0.3) cm2, p < 0.05; maximum gradient 98 (22) mm Hg v 74 (24) mm Hg, p < 0.05). In HCM, hyperenhancement was predominant in the anteroseptal regions and patients with hyperenhancement had higher end diastolic (125.4 (36.9) ml v 98.8 (16.9) ml, p < 0.05) and end systolic volumes (38.9 (18.2) ml v 25.2 (1.7) ml, p < 0.05). The volume of hyperenhancement (percentage of total LV myocardium), where present, was lower in AS than in HCM (4.3 (1.9)% v 8.6 (7.4)%, p< 0.05). Hyperenhancement was observed in 4.5 (3.1) and 4.6 (2.7) segments in AS and HCM, respectively (p  =  0.93), and the enhancement pattern was mostly patchy with multiple foci. Conclusions Focal scarring can be observed in severe LV hypertrophy caused by AS and HCM, and correlates with the severity of LV remodelling. However, focal scarring is significantly less prevalent in adaptive LV hypertrophy caused by AS than in genetically determined HCM. PMID:16606864

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

    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.)

  11. 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)

    1998-09-01

    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.

  12. 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

    2006-10-01

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

  13. Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium.

    Weber, K T; Clark, W A; Janicki, J S; Shroff, S G

    1987-01-01

    The myocardium consists of myocytes and capillaries embedded in a connective tissue matrix. Myocardial mass, which is predominantly a function of myocyte size, is determined by systolic tension; when systolic pressure is gradually elevated above the normal range, mass will increase. The hypertrophic process is a continuum consisting of subtle transitions that take place within the muscular, collagenous, and vascular compartments; these transitions, however, need not be temporarily concordant. We would identify three phases to the hypertrophic process. First, there is an evolutionary phase, whereby the structural and biochemical remodeling of the various compartments of the myocardium is in transition, with each compartment having its own rate of adjustment. During this evolutionary phase, myocardial contractility, as reflected by stress-length and stress-velocity relations, may or may not be normal, but ventricular pump function and O2 delivery are preserved. Second, there is a physiologic phase during which the structural and biochemical remodeling of the compartments reaches a coordinated balance. The myocardial stress-length relation and ventricular function are each normal, but rate-dependent indices of contractility may be abnormal. During the physiologic phase of hypertrophy, the remodeled myocardium will revert to normal when the abnormal loading condition is removed. Finally, there is a pathologic phase. In this phase, compartment remodeling is no longer balanced (e.g., the ratio of structural versus maintenance proteins), and length and rate-dependent indices of myocardial contractility are depressed. Ventricular pump function is also abnormal in the pathologic phase; consequently. O2 delivery to the tissues is impaired. This imbalance in O2 demand and supply may be apparent at rest in more advanced expressions of disease or may appear during the physiologic stress of exercise in less severe disease. In the latter case, the patient's aerobic capacity is reduced to the extent that it can be used to grade the severity of heart failure and to predict the cardiac reserve. During the pathologic phase of hypertrophy, the structural and biochemical remodeling of the myocardium may be irreversible, although this may not be the case for each compartment. Finally, it is important to distinguish cardiac (or myocardial) failure from the clinical syndrome of congestive heart failure. The latter arises from congested organs and hypoperfused tissues; its clinical manifestations are dependent on the activation of the adrenergic nervous and renin-angiotensin-aldosterone systems and the presence of a salt-avid kidney. Congestive heart failure is a late clinical feature of chronic pressure overload and pathologic hypertrophy. PMID:2485029

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

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

  15. Glycogen Synthase Kinase-3β Is a Negative Regulator of Cardiomyocyte Hypertrophy

    Haq, Syed; Choukroun, Gabriel; Kang, Zhao Bin; Ranu, Hardeep; MATSUI, Takashi; Rosenzweig, Anthony; Molkentin, Jeffrey D.; Alessandrini, Alessandro; Woodgett, James; Hajjar, Roger; Michael, Ashour; FORCE, THOMAS

    2000-01-01

    Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes. Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy. Herein, we report that glycogen syn...

  16. Physiologic or pathologic hypertrophy.

    Krayenbuehl, H P; Hess, O M; Schneider, J; Turina, M

    1983-01-01

    Physiologic hypertrophy occurs as the result of exercise conditioning and is characterized by normal or supranormal left ventricular (LV) contractile function and reversibility of structural alterations. Whether hypertrophy produced by chronic abnormal loading can be termed 'physiologic' is a matter of debate because in experimental pressure overload hypertrophy normal in vivo ventricular function may be associated with abnormal in vitro function of the papillary muscles. In patients with moderate LV hypertrophy from aortic valve disease (angiographic mass less than 180 g/m2) ejection fraction (EF) is preserved, but at similar levels of afterload, when mass exceeds 180 g/m2, EF is depressed. Comparison of LV function with myocardial structure (endomyocardial biopsies) has shown that in patients with compensated LV function and those with left heart failure (EF less than 57%, LVEDP greater than 20 mm Hg and/or cardiac index less than 2.5 l/min/m2) interstitial fibrosis (IF) was increased to a similar extent (16 and 18%; normal less than 5%), whereas muscle fiber diameter (MFD; normal less than or equal to 20 mu) was larger (P less than 0.05) in the patients with failure (30 mu) than in those with preserved function (27 mu). Moreover patients with depressed postoperative function had a larger (P less than 0.01) preoperative MFD (35 mu) than those with normal postoperative function (30 mu). Seventeen months after successful aortic valve replacement IF increased (P less than 0.02) and MFD decreased (P less than 0.001) but did not become normal regardless whether postoperative function was normal or depressed. Thus in secondary hypertrophy myocardial structure is pathologic even in the presence of normal LV function and depressed function appears likely to be related to excessive fiber hypertrophy rather than to IF. Massive fiber hypertrophy heralds an unfavorable postoperative LV function and fibrosis is irreversible after surgical correction of the abnormal load. PMID:6220898

  17. Cardiac p300 Is Involved in Myocyte Growth with Decompensated Heart Failure

    Yanazume, Tetsuhiko; Hasegawa, Koji; Morimoto, Tatsuya; Kawamura, Teruhisa; Wada, Hiromichi; Matsumori, Akira; Kawase, Yosuke; Hirai, Maretoshi; Kita, Toru

    2003-01-01

    A variety of stresses on the heart initiate a number of subcellular signaling pathways, which finally reach the nuclei of cardiac myocytes and cause myocyte hypertrophy with heart failure. However, common nuclear pathways that lead to this state are unknown. A zinc finger protein, GATA-4, is one of the transcription factors that mediate changes in gene expression during myocardial-cell hypertrophy. p300 not only acts as a transcriptional coactivator of GATA-4, but also possesses an intrinsic ...

  18. 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...

  19. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients

    Bang, Casper; Gerdts, Eva; Aurigemma, Gerard P; Boman, Kurt; Dahlöf, Björn; Roman, Mary J; Køber, Lars; Wachtell, Kristian; Devereux, Richard B

    2013-01-01

    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...... [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV)] in hypertensive patients....

  20. 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

    2016-03-01

    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 (ICa-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 ICa-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 ICa-L, reversal potential of ICa-L, nor the activation/inactivation of ICa-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 ICa-L in rat cardiomyocytes and negative inotropic effects on myocardial contractility. PMID:26674933

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

    M.A. Carneiro-Júnior

    2010-11-01

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

  2. Cardiac hypertrophy: useful adaptation or pathologic process?

    Grossman, W

    1980-10-01

    An extensive body of evidence supports the concept that cardiac hypertrophy and normal cardiac growth develop in response to increased hemodynamic loading and abnormal systolic and diastolic stresses at the myocardial fiber level. The pattern of hypertrophy reflects the nature of the inciting stress. Experimental studies indicate that if the stress is moderate, gradually applied, and the animal young and healthy, physiologic hypertrophy of muscle with normal contractility develops. In this circumstance, cardiac hypertrophy may be regarded as a useful adaptation to increased hemodynamic loading. When the inciting stress is severe, abruptly applied, or the animal old or debilitated, pathologic hypertrophy develops: in this circumstance, the cardiac muscle produced is abnormal and exhibits depressed contractility. Of particular clinical relevance is the intermediate situation which seems to develop in many patients with chronic left ventricular pressure-overload and perhaps also in left ventricular volume-overload. In this situation, chronic left ventricular pressure or volume overload is initially matched by adequate hypertrophy in the appropriate pattern. Eventually, in some patients, hypertrophy fails to keep pace with the hemodynamic overload so that a systolic stress imbalance occurs at the myocardial fiber level and left ventricular pump failure ensues. If this situation persists uncorrected, it is possible that the increasingly high wall stresses will convert physiologic to pathologic hypertrophy. The task of the clinician is to identify this intermediate stage and to correct the abnormal hemodynamic loading before the transition to pathologic hypertrophy becomes complete. PMID:6448546

  3. 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

    Ahmad, Ashfaq; Sattar, Munavvar A.; Rathore, Hassaan A.; Abdulla, Mohammed H.; Khan, Safia A.; Azam, Maleeha; Abdullah, Nor A.; Johns, Edward J.

    2016-01-01

    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 LVH. Exogenous administration of H2S augmented the reduced renal cortical blood perfusion in the LVH state. PMID:26963622

  4. 123I-metaiodobenzylguanidine imaging of the heart in essential hypertension. The effect of left ventricular hypertrophy and performance reserve upon it

    To study myocardial norepinephrine (NE) activity in essential hypertension (HT) and the effect of left ventricular (LV) hypertrophy and LV performance reserve upon it, myocardial imaging was performed with 123I-metaiodobenzylguanidine (123I-MIBG) and 201Tl at rest in 23 patients with HT and 10 normal subjects. Uptake Ratio (%Uptake of 123I-MIBG in delayed image divided by %Uptake of 201Tl) was calculated as the index of myocardial 123I-MIBG uptake. Reduction of myocardial 123I-MIBG during 3h (WOR) was also calculated. The defect from the Bull's-eye map was quantitatively assessed as Defect Score. Patients were divided into 2 groups according to the LV mass (LVM) by echocardiography. Uptake Ratio was lower in Group I (LVM>l30g/m2, n=16) than that Group II (LVM2, n=7). WOR was accelerated in Group I than Group II. Uptake Ratio and WOR were identical between Group II and normal subjects. The incidence of 123I-MIBG defect and Defect Score were significantly greater in Group I (incidence: 94%, Defect Score: 3.0±1.3) than Group II (incidence: 43%, Defect Score: 1.1±0.6). To study the effect of LV performance reserve, patients were divided into 2 groups according to LV ejection fraction (EF) responses to exercise stress (Ex) obtained by 99mTc blood pool imaging. LVEF increased by Ex in 13 patients (Group A) and decreased or did not change by Ex in 7 (Group B). Uptake Ratio was significantly smaller and WOR was significantly accelerated in Group B than Group A and normal subjects. The incidence of 123I-MIBG defect and Defect Score were greater in Group B than Group A, with no significant difference. LVM and LVEF response seemed to influence upon myocardial NE kinetics independently. These results suggested that LVM and LV performance reserve influenced upon myocardial NE kinetics in HT patients and quantitative analysis of 123I-MIBG imaging may be helpful for assessing HT prognosis. (J.P.N.)

  5. 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

    2003-12-01

    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, more female patients were involved in group C. The mean age of group C patients compared to group B was also significantly higher (P<0.001) even though no significant age difference was noted between group C and group A patients. It is concluded that Nigerians with ECG-LVH with ST-T waves changes have increased risk of cardiovascular risk factors compared to normal group A patients and even patients with EGC-LVH (group B) alone. Hence, they represent subset of patients to be aggressively followed up with multiple risk factors intervention. PMID:15259925

  6. Visualization of hypertrophied papillary muscle mimicking left ventricular mass on gated blood pool and T1-201 myocardial perfusion imaging

    A sixty-year old man with acute myocardial infarction was incidentally found to have a hypertrophied anterolateral papillary muscle (ALPPM) of the left ventricle on gated blood pool (GBP) and T1-201 myocardial perfusion images. Hypertrophy of the ALPPM was visualized as a movable defect in the lateral basal area on GBP imaging throughout the cardiac cycle and on the TI-201 study as a radionuclide accumulating structure, consistent with the defect in the GBP. A combination of these findings may suggest the presence of a hypertrophied papillary muscle of the left ventricle

  7. Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy

    Elhendy, A.; Geleijnse, M.L.; Van Domburg, R.T.; Bax, J.J.; Nierop, P.R.; Beerens, S.A.M.; Mohsen Ibrahim, M.; Roelandt, J.R.T.C. [Thoraxcenter, University Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands); Valkema, R.; Krenning, E.P. [Department of Nuclear Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands)

    1998-01-01

    The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine stress echocardiography in conjunction with sestamibi (MIBI) SPET was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Significant coronary artery disease ({>=}50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%-82%), 83% (CI 75%-91%) and 75% (CI 66%-84%), those for MIBI were 67% (CI 57%-77%), 83% (CI 75%-91%) and 70% (CI 60%-80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%-69%), 90% (CI 86%-94%) and 77% (CI 72%-82%). Those for MIBI were 58% (CI 51%-64%), 91% (CI 87%-94%) and 75% (CI 69%-80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET.(orig./MG) (orig.) With 2 figs., 4 tabs., 39 refs.

  8. Asymmetric septal hypertrophy and hypothyroidism in children.

    Altman, D I; Murray, J.; S Milner; Dansky, R; Levin, S E

    1985-01-01

    Any echocardiographic study of two children with hypothyroidism demonstrated the presence of asymmetric septal hypertrophy. One child died aged 11 months, and pronounced thickening of the interventricular septum was confirmed at necropsy. There was also hypertrophy of the left ventricular free wall. Histological examination showed only slight muscle fibre disarray, but there was striking vacuolation and hypertrophy of muscle fibres. In the second case, a child aged five years, the asymmetric ...

  9. 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

    2012-01-01

    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 ...

  10. Tafazzin knockdown interrupts cell cycle progression in cultured neonatal ventricular fibroblasts.

    He, Quan; Wang, Miao; Harris, Nicole; Han, Xianlin

    2013-11-01

    Mutation of the mitochondrial protein tafazzin causes dilated cardiomyopathy in Barth syndrome. Previous studies have shown that tafazzin knockdown promotes hypertrophy of neonatal cardiac myocytes. The current investigation was designed to show whether tafazzin knockdown affects cardiac fibroblast proliferation and collagen secretion, which contribute to fibrosis in dilated cardiomyopathy. In primary cultures of neonatal ventricular fibroblasts (NVFs) transduced with a tafazzin short hairpin RNA adenovirus, tafazzin knockdown increased production of reactive oxygen species and activation of mitogen-activated protein kinases and induced protein and DNA synthesis via cell cycle regulators. It also reduced intracellular ATP, activated AMPK, and caused multinucleation, hypertrophy, and enhanced collagen secretion. We concluded that tafazzin knockdown interrupts the NVF cell cycle and this in turn may contribute to fibrosis and dilated cardiomyopathy in Barth syndrome. PMID:23997105

  11. Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension.

    Kontaraki, Joanna E; Marketou, Maria E; Parthenakis, Fragiskos I; Maragkoudakis, Spyros; Zacharis, Evangelos A; Petousis, Stelios; Kochiadakis, George E; Vardas, Panos E

    2015-10-01

    MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 ± 0.50 vs. 13.20 ± 2.15, P hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease. PMID:26358152

  12. The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling*

    Skurk, Carsten; Izumiya, Yasuhiro; Maatz, Henrike; Razeghi, Peter; Shiojima, Ichiro; Sandri, Marco; Sato, Kaori; Zeng, Ling; Schiekofer, Stephan; Pimentel, David; Lecker, Stewart; Taegtmeyer, Heinrich; Goldberg, Alfred L.; Walsh, Kenneth

    2005-01-01

    Although signaling mechanisms inducing cardiac hypertrophy have been extensively studied, little is known about the mechanisms that reverse cardiac hypertrophy. Here, we describe the existence of a similar Akt/forkhead signaling axis in cardiac myocytes in vitro and in vivo, which is regulated by insulin, insulin-like growth factor (IGF), stretch, pressure overload, and angiotensin II stimulation. FOXO3a gene transfer prevented both IGF and stretch-induced hypertrophy in rat neonatal cardiac ...

  13. Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations

    DanutaSzczesna-Cordary

    2014-09-01

    Full Text Available Cardiac hypertrophy represents one of the most important cardiovascular problems yet the mechanisms responsible for hypertrophic remodeling of the heart are poorly understood. In this report we aimed to explore the molecular pathways leading to two different phenotypes of cardiac hypertrophy in transgenic mice carrying mutations in the human ventricular myosin essential light chain (ELC. Mutation-induced alterations in the heart structure and function were studied in two transgenic (Tg mouse models carrying the A57G (alanine to glycine substitution or lacking the N-terminal 43 amino acid residues (Δ43 from the ELC sequence. The first model represents an HCM disease as the A57G mutation was shown to cause malignant HCM outcomes in humans. The second mouse model is lacking the region of the ELC that was shown to be important for a direct interaction between the ELC and actin during muscle contraction. Our earlier studies demonstrated that >7 month old Tg-Δ43 mice developed substantial cardiac hypertrophy with no signs of histopathology or fibrosis. Tg mice did not show abnormal cardiac function compared to Tg-WT expressing the full length human ventricular ELC. Previously reported pathological morphology in Tg-A57G mice included extensive disorganization of myocytes and interstitial fibrosis with no abnormal increase in heart mass observed in >6 month-old animals. In this report we show that strenuous exercise can trigger hypertrophy and pathologic cardiac remodeling in Tg-A57G mice as early as 3 months of age. In contrast, no exercise-induced changes were noted for Tg-Δ43 hearts and the mice maintained a non-pathological cardiac phenotype. Based on our results, we suggest that exercise-elicited heart remodeling in Tg-A57G mice follows the pathological pathway leading to HCM, while it induces no abnormal response in Tg-Δ43 mice.

  14. Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy.

    Dobrzyn, Pawel; Pyrkowska, Aleksandra; Duda, Monika K; Bednarski, Tomasz; Maczewski, Michal; Langfort, Jozef; Dobrzyn, Agnieszka

    2013-06-15

    Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser(565), and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future. PMID:23632628

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

    Erling David Kaunang; Jane G. C. Metusala; Audrey M.I. Wahani

    2014-01-01

    Background Systematic exercise leads to increased left ventricular mass, which may be misleading in a differential diagnosis of heart disease in athletes (physiologic hypertrophy versus pathologic hypertrophy). The cause of left ventricular hypertrophy is an important risk factor in the morbidity and mortality of cardiovascular diseases. Objective To compare left ventricular mass and left ventricular hypertrophy in male adolescent athletes and non-athletes. Methods We conducted a cros...

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

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

  17. Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy

    Taigen, Tyler; de Windt, Leon J; Lim, Hae W.; Molkentin, Jeffery D

    2000-01-01

    Cardiac hypertrophy is a major predictor of future morbidity and mortality. Recent investigation has centered around identifying the molecular signaling pathways that regulate cardiac myocyte reactivity with the goal of modulating pathologic hypertrophic programs. One potential regulator of cardiomyocyte hypertrophy is the calcium-sensitive phosphatase calcineurin. We show here that calcineurin enzymatic activity, mRNA, and protein levels are increased in cultured neonatal rat cardiomyocytes ...

  18. The effect of cardiac hypertrophy on the coronary collateral circulation.

    Harrison, D G; Barnes, D H; Hiratzka, L F; Eastham, C L; Kerber, R E; Marcus, M L

    1985-06-01

    We have previously shown that dogs with renal hypertension and left ventricular hypertrophy have larger infarcts (per risk area size) than do control animals. A potential explanation for this is that collateral resistance is higher in these dogs. Paradoxically, previous postmortem studies in human hearts with left ventricular hypertrophy have suggested that coronary collaterals are actually increased in this condition. To test the hypothesis that left ventricular hypertrophy is associated with alterations in coronary collateral resistance, studies were performed in dogs with renal hypertension and left ventricular hypertrophy and in patients with aortic valvular disease at the time of cardiac surgery. With an isolated, adenosine-vasodilated, blood-perfused cardiac preparation, collateral and normal zone pressure-flow relationships were established by means of radioactive microspheres in nine dogs with renal hypertension and left ventricular hypertrophy and in 17 controls. Collateral resistance calculated from these pressure-flow relationships were similar in both groups (4.0 +/- 0.7 in dogs with renal hypertension and left ventricular hypertrophy and 3.9 +/- 0.4 mm Hg/ml/min/100 g in controls). In addition, normal zone resistance was not different between groups (transmural resistances 0.17 +/- 0.01 in controls and 0.18 +/- 0.02 in dogs with renal hypertension and left ventricular hypertrophy. In five patients with aortic valve disease, left ventricular hypertrophy, and normal coronary arteries and in six patients without left ventricular hypertrophy who had normal left anterior descending coronary arteries, a 7 MHz suction-mounted echo transducer was used to monitor systolic wall thickening during transient occlusions of the left anterior descending artery at the time of cardiac surgery. Because noncollateralized myocardium ceases to contract promptly after coronary occlusion, this approach provides an indirect index of collateral perfusion. Twenty seconds after the onset of coronary occlusion, systolic thickening had markedly decreased in both groups (15 +/- 10% of control values in nonhypertrophied hearts and 10 +/- 10% in hearts with left ventricular hypertrophy; p = NS between groups). Thus the severity of contraction abnormality induced during transient coronary occlusion in these two groups of patients was similar, suggesting that the degree of severity of ischemia was comparable between the two groups. We conclude that collateral resistance is not altered by hypertension and left ventricular hypertrophy and that left ventricular hypertrophy in patients is not associated with functional evidence of an enhanced collateral circulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3158452

  19. O eletrocardiograma no diagnstico da hipertrofia ventricular de pacientes com doena renal crnica / Electrocardiography in the diagnosis of ventricular hypertrophy in patients with chronic renal disease / El electrocardiograma en el diagnstico de la hipertrofia ventricular de pacientes con enfermedad renal crnica

    Francisco de Assis, Costa; Ivan Romero, Rivera; Mirian Lira Castro de, Vasconcelos; Andr Falco Pedrosa, Costa; Rui Manoel dos Santos, Pvoa; Maria Tereza Nogueira, Bombig; Brulio, Luna Filho; Valter Correia de, Lima.

    2009-10-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) um fator preditor independente de risco cardiovascular e sua caracterizao e prevalncia na doena renal crnica (DRC) carecem de melhor estudo. OBJETIVO: Estabelecer o diagnstico de HVE em pacientes com DRC em estgio 5 por seis diferentes cr [...] itrios eletrocardiogrficos, correlacionando-os com o ndice de massa do ventrculo esquerdo (IMVE) obtido pelo ecocardiograma. MTODOS: Estudo transversal que incluiu 100 pacientes (58 homens e 42 mulheres, idade de 46,2 14,0 anos) com DRC de todas as etiologias, h pelo menos seis meses em hemodilise (HD). Foram obtidos eletrocardiograma (ECG) e ecocardiograma dos pacientes, sempre at uma hora aps o trmino das sesses de HD. RESULTADOS: A HVE foi detectada em 83 pacientes (83%), dos quais 56 (67,4%) apresentavam o padro concntrico e 27 (32,6%) o padro excntrico de HVE. Todos os mtodos eletrocardiogrficos estudados tiveram sensibilidade, especificidade e acurcia diagnsticas acima de 50%. Pela correlao linear de Pearson com o IMVE, apenas o critrio de Sokolow-Lyon voltagem no apresentou coeficiente > 0,50. J o clculo da razo de verossimilhana mostrou que o ECG possui poder discriminatrio para diagnstico de HVE na populao estudada, com nfase para os critrios de Cornell produto e Romhilt-Estes. No houve correlao entre IMVE com o QTc e sua disperso. CONCLUSO: O ECG um mtodo til, eficaz e de alta reprodutibilidade no diagnstico de HVE dos pacientes em HD. Nessa populao, o critrio de Cornell produto mostrou-se o mais fidedigno para a deteco de HVE. Abstract in spanish FUNDAMENTO: La hipertrofia ventricular izquierda (HVI) es un factor predictor independiente de riesgo cardiovascular y su caracterizacin y prevalencia en la enfermedad renal crnica (ERC) carecen de mejor estudio. OBJETIVO: Establecer el diagnstico de HVI en pacientes con ERC en estadio 5 por seis [...] diferentes criterios electrocardiogrficos, correlacionndolos al ndice de masa del ventrculo izquierdo (IMVI) que se obtuvo mediante el ecocardiograma. MTODOS: Estudio transversal que incluy a 100 pacientes (58 varones y 42 mujeres, edad de 46,2 14,0 aos) con ERC de todas las etiologas, desde hace al menos 6 meses en hemodilisis (HD). Se obtuvieron electrocardiograma (ECG) y ecocardiograma de los pacientes, siempre hasta una hora tras el trmino de las sesiones de HD. RESULTADOS: La HVI se detect en 83 pacientes (83%), de los que 56 (67,4%) presentaban el estndar concntrico y 27 (32,6%) el estndar excntrico de HVI. Todos los mtodos electrocardiogrficos estudiados tuvieron sensibilidad, especificidad y exactitud diagnsticas superiores al 50%. Mediante la correlacin lineal de Pearson con el IMVI, solamente el criterio de Sokolow-Lyon voltaje no present coeficiente > 0,50. Sin embargo, el clculo de la razn de verosimilitud evidenci que el ECG tiene poder discriminatorio para diagnstico de HVI en la poblacin estudiada, con nfasis para los criterios de Producto de Cornell y Romhilt-Estes. No hubo correlacin entre IMVI con el QTc y su dispersin. CONCLUSIN: El ECG es un mtodo til, eficaz y de alta reproductibilidad en el diagnstico de HVI de los pacientes en HD. En esa poblacin, el criterio de Producto de Cornell fue ms fiable para la deteccin de HVI. Abstract in english 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 electroca [...] rdiographic 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. Electrocard

  20. Hypertrophied hearts: what of sevoflurane cardioprotection?

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael; Christensen, Sara Dahl; Sivesgaard, Kim; Torp, Peter; Sloth, Erik

    2009-01-01

    cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane...... reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated...... ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts....

  1. 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

    2011-01-01

    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 global as well as regional systolic dysfunction, and might be used as new additional tool for the differentiation between physiologic and pathologic LVH. PMID:20623194

  2. 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

    1999-10-15

    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. PMID:10532505

  3. Detection of impaired fatty acid metabolism in right ventricular hypertrophy. Assessment by I-123 ?-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography

    The subjects consisted of 6 patients with chronic obstructive pulmonary disease, 4 with primary pulmonary hypertension, 2 each with refractory pulmonary tuberculosis, tricuspid insufficiency, pulmonary embolism, 1 each with atrial septal defect, ventricular septal defect (Eisenmenger complex), Ebstein anomaly, and endocardial defect, and 7 healthy controls. SPECT imaging with Tl-201 (Tl) and I-123 BMIPP, and Tc-99m RBC first pass and gated blood pool scintigraphy were performed. Based on Tl planar images, the subjects were classified into 3 groups: 7 patients with no RV visualization (Group A), 11 with moderate RV visualization (Group B) and 9 with marked RV visualization (Group C). As a semi-quantitative evaluation by a myocardial SPECT, 3 regions in 3 representative short axial images were divided into 9 segments, each of which was graded from 0 to +3, and their sum was calculated as the RV score. The right ventricular ejection fraction (RVEF and the left ventricular ejection fraction were obtained by Tc-99m RBC cardiac scintigraphy. The groups with marked visualization of the right ventricle had lower RVEF, and there was a good correlation between the RVEF and the RV score with both a and BMIPP. Although a good correlation was demonstrated between the RV score with Tl and BMIPP in Groups A and B, in Group C, in which there was marked RV Tl visualization, the RV score with BMIPP was significantly smaller than with Tl. These findings suggest that impaired fatty acid metabolism may exist in severely hypertrophic right ventricle due to RV overload. (K.H.)

  4. Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-β

    Teekakirikul, Polakit; Eminaga, Seda; Toka, Okan; Alcalai, Ronny; Wang, Libin; Wakimoto, Hiroko; Nayor, Matthew; Konno, Tetsuo; Gorham, Joshua M.; Wolf, Cordula M; Kim, Jae B.; Schmitt, Joachim P.; Molkentin, Jefferey D.; Norris, Russell A.; Tager, Andrew M.

    2010-01-01

    Mutations in sarcomere protein genes can cause hypertrophic cardiomyopathy (HCM), a disorder characterized by myocyte enlargement, fibrosis, and impaired ventricular relaxation. Here, we demonstrate that sarcomere protein gene mutations activate proliferative and profibrotic signals in non-myocyte cells to produce pathologic remodeling in HCM. Gene expression analyses of non-myocyte cells isolated from HCM mouse hearts showed increased levels of RNAs encoding cell-cycle proteins, Tgf-β, perio...

  5. Akt activation induces hypertrophy without contractile phenotypic maturation in airway smooth muscle

    Ma, Lan; Brown, Melanie; Kogut, Paul; Serban, Karina; Li, Xiaojing; McConville, John; Chen, Bohao; Bentley, J. Kelley; Hershenson, Marc B.; Dulin, Nickolai; Solway, Julian; Camoretti-Mercado, Blanca

    2011-01-01

    Airway smooth muscle (ASM) hypertrophy is a cardinal feature of severe asthma, but the underlying molecular mechanisms remain uncertain. Forced protein kinase B/Akt 1 activation is known to induce myocyte hypertrophy in other muscle types, and, since a number of mediators present in asthmatic airways can activate Akt signaling, we hypothesized that Akt activation could contribute to ASM hypertrophy in asthma. To test this hypothesis, we evaluated whether Akt activation occurs naturally within...

  6. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M.; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

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

    G. R. Hoppen

    2000-10-01

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

  8. Cardiac p300 Is Involved in Myocyte Growth with Decompensated Heart Failure

    Yanazume, Tetsuhiko; Hasegawa, Koji; Morimoto, Tatsuya; Kawamura, Teruhisa; Wada, Hiromichi; Matsumori, Akira; Kawase, Yosuke; Hirai, Maretoshi; Kita, Toru

    2003-01-01

    A variety of stresses on the heart initiate a number of subcellular signaling pathways, which finally reach the nuclei of cardiac myocytes and cause myocyte hypertrophy with heart failure. However, common nuclear pathways that lead to this state are unknown. A zinc finger protein, GATA-4, is one of the transcription factors that mediate changes in gene expression during myocardial-cell hypertrophy. p300 not only acts as a transcriptional coactivator of GATA-4, but also possesses an intrinsic histone acetyltransferase activity. In primary cardiac myocytes derived from neonatal rats, we show that stimulation with phenylephrine increased an acetylated form of GATA-4 and its DNA-binding activity, as well as expression of p300. A dominant-negative mutant of p300 suppressed phenylephrine-induced nuclear acetylation, activation of GATA-4-dependent endothelin-1 promoters, and hypertrophic responses, such as increase in cell size and sarcomere organization. In sharp contrast to the activation of cardiac MEK-1, which phosphorylates GATA-4 and causes compensated hypertrophy in vivo, p300-mediated acetylation of mouse cardiac nuclear proteins, including GATA-4, results in marked eccentric dilatation and systolic dysfunction. These findings suggest that p300-mediated nuclear acetylation plays a critical role in the development of myocyte hypertrophy and represents a pathway that leads to decompensated heart failure. PMID:12724418

  9. ?-Adrenergic Receptor Stimulation Induces Endoplasmic Reticulum Stress in Adult Cardiac Myocytes: Role in Apoptosis

    Dalal, Suman; Foster, Cerrone R.; Bhudev C Das; Singh, Mahipal; Singh, Krishna

    2012-01-01

    Accumulation of misfolded proteins and alterations in calcium homeostasis induces endoplasmic reticulum (ER) stress, leading to apoptosis. Here we tested the hypothesis that ?-AR stimulation induces ER stress, and induction of ER stress plays a pro-apoptotic role in cardiac myocytes. Using thapsigargin and brefeldin A, we demonstrate that ER stress induces apoptosis in adult rat ventricular myocytes (ARVMs). ?-AR-stimulation (isoproterenol; 3h) significantly increased expression of ER stress ...

  10. Contractile activity and cell-cell contact regulate myofibrillar organization in cultured cardiac myocytes

    1993-01-01

    Adult feline ventricular myocytes cultured on a laminin-coated substratum reestablish intercellular junctions, yet disassemble their myofibrils. Immunofluorescence microscopy reveals that these non- beating heart cells lack vinculin-positive focal adhesions; moreover, intercellular junctions are also devoid of vinculin. When these quiescent myocytes are stimulated to contract with the beta-adrenergic agonist, isoproterenol, extensive vinculin-positive focal adhesions and intercellular junctio...

  11. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

  12. The Positive Transcription Elongation Factor b Is an Essential Cofactor for the Activation of Transcription by Myocyte Enhancer Factor 2

    Nojima, Masanori; Huang, Yehong; Tyagi, Mudit; Kao, Hung-Ying; Fujinaga, Koh

    2008-01-01

    The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyt...

  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

    2015-01-01

    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. Long Pentraxin PTX3 Exacerbates Pressure Overload–Induced Left Ventricular Dysfunction

    Suzuki, Satoshi; Shishido, Tetsuro; Funayama, Akira; Netsu, Shunsuke; Ishino, Mitsunori; Kitahara, Tatsuro; Sasaki, Toshiki; Katoh, Shigehiko; Otaki, Yoichiro; Watanabe, Tetsu; Shibata, Yoko; Mantovani, Alberto; Takeishi, Yasuchika; Kubota, Isao

    2013-01-01

    Background Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. Methods and Results PTX3 systemic knockout (PTX3-KO) mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG), and the respective wild-type (WT) littermate mice were subjected to transverse aortic constriction (TAC) or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal–regulated kinase 1/2 (ERK1/2) in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. Conclusion The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload. PMID:23372656

  15. 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

    2009-10-01

    Full Text Available FUNDAMENTO: A hipertrofia ventricular esquerda (HVE é um fator preditor independente de risco cardiovascular e sua caracterização e prevalência na doença renal crônica (DRC carecem de melhor estudo. OBJETIVO: Estabelecer o diagnóstico de HVE em pacientes com DRC em estágio 5 por seis diferentes critérios eletrocardiográficos, correlacionando-os com o índice de massa do ventrículo esquerdo (IMVE obtido pelo ecocardiograma. MÉTODOS: Estudo transversal que incluiu 100 pacientes (58 homens e 42 mulheres, idade de 46,2 ± 14,0 anos com DRC de todas as etiologias, há pelo menos seis meses em hemodiálise (HD. Foram obtidos eletrocardiograma (ECG e ecocardiograma dos pacientes, sempre até uma hora após o término das sessões de HD. RESULTADOS: A HVE foi detectada em 83 pacientes (83%, dos quais 56 (67,4% apresentavam o padrão concêntrico e 27 (32,6% o padrão excêntrico de HVE. Todos os métodos eletrocardiográficos estudados tiveram sensibilidade, especificidade e acurácia diagnósticas acima de 50%. Pela correlação linear de Pearson com o IMVE, apenas o critério de Sokolow-Lyon voltagem não apresentou coeficiente > 0,50. Já o cálculo da razão de verossimilhança mostrou que o ECG possui poder discriminatório para diagnóstico de HVE na população estudada, com ênfase para os critérios de Cornell produto e Romhilt-Estes. Não houve correlação entre IMVE com o QTc e sua dispersão. CONCLUSÃO: O ECG é um método útil, eficaz e de alta reprodutibilidade no diagnóstico de HVE dos pacientes em HD. Nessa população, o critério de Cornell produto mostrou-se o mais fidedigno para a detecção de HVE.FUNDAMENTO: La hipertrofia ventricular izquierda (HVI es un factor predictor independiente de riesgo cardiovascular y su caracterización y prevalencia en la enfermedad renal crónica (ERC carecen de mejor estudio. OBJETIVO: Establecer el diagnóstico de HVI en pacientes con ERC en estadio 5 por seis diferentes criterios 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. Electrocardiography (ECG and echocardiography were performed in all patients, always up to one hour after the end of the HD sessions. RESULTS: LVH was detected in 83 patients (83%, of whom 56 (67.4% had the concentric pattern and 27 (32.6% the eccentric pattern of LVH. Diagnostic sensitivity, specificity and accuracy of all the electrocardiographic methods studied were higher than 50%. Using Pearson's linear correlation for LVMI, only the Sokolow-Lyon voltage criterion did not show a > 0.50 coefficient. Calculation of the likelihood ratio, in turn, showed that ECG has a discriminatory power for the diagnosis of LVH in the population studied, with emphasis on the Cornell-product and Romhilt-Estes criteria. No correlation was observed between LVMI and QTc and QTc dispersion. CONCLUSION: ECG is a useful, efficient, and highly reproducible method for the diagnosis of LVH in HD patients. In this population, the Cornell-product proved to be the most reliable criterion for the detection of LVH.

  16. Virginal hypertrophy.

    Ryan, R F; Pernoll, M L

    1985-05-01

    A patient with extensive juvenile hypertrophy of the breasts has been presented. Several interesting facts in the case history are as follows: After pregnancy, the breasts did not regress with "hormone shots" to stop lactation. The patient took high-dosage estrogen birth control pills for 3 years before the breasts started to grow rapidly. Within 1 month after reduction mammaplasty and despite 20 mg dydrogesterone per day, the breasts started to enlarge. A total of 60 mg b.i.d. of dydrogesterone did not stop breast regrowth. Tamoxifen citrate did cause regression of the breasts. After two reductions, the breasts regrew with a subsequent pregnancy. The breast tissue regrew in the axilla with a subsequent pregnancy after simple mastectomy-subcutaneous mastectomy and free nipple transplants. Chronic marijuana use may have an effect on the breast tissue in certain susceptible females as well as in some males. Much needs to be learned about the control of growth of female breast tissue. PMID:3983282

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

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

    2012-01-01

    FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esquerda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguido...

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

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

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

    Ulises Novoa

    2010-08-01

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

  20. 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

    1997-12-01

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

  1. Pharmacological targeting of CDK9 in cardiac hypertrophy

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

    2010-01-01

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

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

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

  3. Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico Factors and mechanisms involved in left ventricular hypertrophy and the anti-hypertrophic role of nitric oxide

    José Antonio Dias Garcia

    2008-06-01

    Full Text Available A hipertrofia ventricular esquerda (HVE ocorre em reposta à sobrecarga hemodinâmica relatada em várias condições fisiológicas e patológicas. Entretanto, ainda não está completamente elucidado se o estímulo primário para a hipertrofia é o estiramento mecânico do coração, fatores neuro-humorais, ou mesmo a interação de ambos. Esses fatores são traduzidos no interior da célula como alterações bioquímicas que levam à ativação de segundos (citosólicos e terceiros (nucleares mensageiros que irão agir no núcleo da célula, regulando a transcrição, e finalmente determinarão a expressão gênica que induza HVE. A HVE é caracterizada por alterações estruturais decorrentes do aumento das dimensões dos cardiomiócitos, da proliferação do tecido conjuntivo intersticial e da rarefação da microcirculação coronariana. Nos últimos anos, o óxido nítrico (•NO surgiu como um importante regulador do remodelamento cardíaco, especificamente reconhecido como um mediador anti-hipertrófico. Vários estudos têm demonstrado os alvos celulares, as vias de sinalização anti-hipertrófica e o papel funcional do •NO. Portanto, a HVE parece desenvolver-se em decorrência da perda do balanço entre as vias de sinalização pró e anti-hipertróficas. Esses novos conhecimentos sobre as vias de sinalização pró e anti-hipertróficas permitirão desenvolver novas estratégicas no tratamento das HVE patológicas.The left ventricular hypertrophy (LVH occurs in response to the hemodynamic overload in some physiological and pathological conditions. However, it has not been completely elucidated whether the primary stimulation for the hypertrophy is the mechanical stretching of the heart, neurohumoral factors, or even the interaction of both. These factors are translated inside the cell as biochemical alterations that lead to the activation of second (cytosolic and third (nuclear messengers that will act in the cell nucleus, regulating transcription, and will finally determine the genic expression that induces LVH. The LVH is characterized by structural alterations due to the increase in the cardiomyocyte dimensions, the proliferation of the interstitial connective tissue and the rarefaction of the coronary microcirculation. Recently, nitric oxide (•NO has appeared as an important regulator of cardiac remodeling, specifically recognized as an anti-hypertrophic mediator. Some studies have demonstrated the cellular targets, the anti-hypertrophic signaling pathways and the functional role of •NO. Thus, the LVH seems to develop as a result of the loss of the balance between the pro and the anti-hypertrophic signaling pathways. This new knowledge about the pro and anti-hypertrophic signaling pathways will allow the development of new strategies in the treatment of pathological LVH.

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

    Laks, M M

    1989-12-01

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

  5. Adenoid hypertrophy presenting with systemic hypertension

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

    2007-01-01

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

  6. Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy

    Liu, Yonggang; Chien, Wei-Ming; Medvedev, Ivan O.; Weldy, Chad S.; Luchtel, Daniel L; Rosenfeld, Michael E.; Chin, Michael T.

    2013-01-01

    Background Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse b...

  7. Induction and analysis of cardiac hypertrophy in transgenic animal models.

    Barbosa, Marcos E; Alenina, Natalia; Bader, Michael

    2005-01-01

    Myocardial hypertrophy is an adaptational process of the heart to increased workload caused by mechanical stress, growth factors, cytokines, catecholamines, or primary genetic abnormalities. Chronic induction of hypertrophy leads to the gradual deterioration of ventricular function and is an independent risk factor for cardiac-related morbidity and mortality in patients with hypertension and ventricular arrythmias. Transgenic animals are very useful models to study the factors involved in the pathogenesis of cardiac hypertrophy. To achieve this goal, rodents lacking or overexpressing a specific gene are subjected to banding of the abdominal aorta, an experimental model of cardiac hypertrophy that leads to pressure overload on the heart. After periods between 3 and 21 d, parameters such as cardiac hemodynamics, morphologic alterations, and expression of marker genes (e.g., the gene for atrial natriuretic peptide) are analyzed in genetically modified animals and compared with controls elucidating a possible implication of the modified gene in the pathogenic process leading to myocardial hypertrophy. This article summarizes the techniques necessary to induce left ventricular hypertrophy by aortic banding and to analyze the effects of this experimental model on hemodynamics, cardiac morphology, and gene expression of transgenic and control animals. PMID:16010028

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

    Srgio Lamgo Rodrigues

    2008-01-01

    Full Text Available FUNDAMENTO: A hipertrofia do ventrculo esquerdo (HVE detectada pela eletrocardiografia um forte preditor de morbidade e mortalidade cardiovasculares. OBJETIVO: Analisar o desempenho dos critrios de Sokolow-Lyon-Rappaport (SLR e de Cornell, em amostra populacional, em relao ao diagnstico de HVE ecocardiografia. MTODOS: Entre os 682 participantes da segunda fase do Projeto MONICA-OMS/Vitria, 641 foram avaliados por meio de eletrocardiografia e ecocardiografia. O subgrupo de indivduos saudveis (n = 269 foi usado para gerar valores de referncia da massa do ventrculo esquerdo (MVE. As sensibilidades e especificidades dos critrios eletrocardiogrficos foram determinadas pela curva ROC (receptor-operator characteristics em relao ao diagnstico de HVE definido pelo critrio ecocardiogrfico interno (MVE > 48 g/m2,7 e 46 g/m2,7 para homens e mulheres, respectivamente. RESULTADOS: A prevalncia de HVE ecocardiografia foi de 23,7% na amostra global, em que havia 49% de hipertensos. O critrio de Cornell apresentou melhor associao 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-Vitria project were assessed using electrocardiogram and echocardiogram. A subgroup of healthy individuals (n=269 was used to generate reference values of LV mass (LVM. Sensitivities and specificities of the electrocardiographic criteria were determined by the ROC (receptor-operator characteristics curve in relation to the diagnosis of LVH, as defined by the internal echocardiographic criterion (LVM > 48 and 46 g/m2.7 for males and females, respectively. RESULTS: The prevalence of LVH as detected by ECHO was 23.7% in the total sample, in which 49% of the individuals were hypertensive. The Cornell criterion showed a better association with the LVM as estimated by ECHO (r= 0.37, p < 0.01 than the SLR criterion (r= 0.19 as well as a better performance in the analysis of the area under the ROC curve. The new cut-off points for the internally-defined Cornell voltage criterion (2.3 mV for males and 1.9 mV for females showed an acceptable combination of sensitivity (22.5 and 28% for males and females, respectively, with a high specificity (95%. CONLUSION: The classic SLR and Cornell voltage criteria showed a low performance in relation to LVH as detected by the ECHO. However, this accuracy may be improved by using the Cornell voltage criteria defined in the present study.

  9. Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

    Kinnunen, P.; Taskinen, T.; Leppäluoto, J; Ruskoaho, H

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontane...

  10. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas; Sogaard, Peter; Chakir, Khalid; Eskesen, Kristian; Steenbergen, Charles; Kass, David A; Abraham, Theodore P

    2013-01-01

    The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one...... 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....

  11. Physiologic or pathologic hypertrophy: how can we know?

    Lai, Emily J; Rakowski, Harry

    2014-08-01

    Pathologic left ventricular hypertrophy due to hypertrophic cardiomyopathy is typically diagnosed based on compatible clinical and imaging findings. In a subset of patients however, the diagnosis is unclear, either due to the finding of concentric hypertrophy raising the possibility of physiologic hypertrophy due to athlete's heart or due to the potential of so-called hypertrophic cardiomyopathy 'phenocopies', which include Anderson-Fabry disease and cardiac amyloidosis. We review each of these diseases, highlighting important distinguishing features, the knowledge of which should permit the resolution of such diagnostic dilemmas. PMID:24972675

  12. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice

    Trentin-Sonoda, Mayra; da Silva, Rogério Cirino; Kmit, Fernanda Vieira; Abrahão, Mariana Vieira; Monnerat Cahli, Gustavo; Brasil, Guilherme Visconde; Muzi-Filho, Humberto; Silva, Paulo André; Tovar-Moll, Fernanda Freire; Vieyra, Adalberto; Medei, Emiliano; Carneiro-Ramos, Marcela Sorelli

    2015-01-01

    We investigated whether the pathways linked to Toll-like receptors 2 and 4 (TLRs) are involved in renal ischemia-reperfusion (I/R)-induced cardiac hypertrophy. Wild type (WT) C57BL/6J, TLR2-/- and TLR4-/- mice were subjected to left kidney ischemia for 60 min followed by reperfusion for 5, 8, 12 and 15 days. Proton density magnetic resonance showed alterations in the injured kidney from WT mice, together with signs of parenchymal edema and higher levels of vimentin mRNA, accompanied by: (i) small, but significant, increase in serum urea after 24 h, (ii) 100% increase in serum creatinine at 24 h. A serum peak of inflammatory cytokines occurred after 5 days of reperfusion. Heart weight/body weight and heart weight/tibia length ratios increased after 12 and 15 days of reperfusion, respectively. Cardiac hypertrophy markers, B-type natriuretic peptide (BNP) and α-actin, left ventricle mass, cardiac wall thickness and myocyte width increased after 15 days of reperfusion, together with longer QTc and action potential duration. Cardiac TLRs, MyD88, HSP60 and HSP70 mRNA levels also increased. After 15 days of reperfusion, absence of TLRs prevented cardiac hypertrophy, as reflected by similar values of left ventricular cardiac mass and heart weight/body weight ratio compared to the transgenic Sham. Renal tissular injury also ameliorated in both knockout mice, as revealed by the comparison of their vimentin mRNA levels with those found in the WT on the same day after I/R. The I/R TLR2-/- group had TNF-α, IFN-γ and IL-1β levels similar to the non-I/R group, whereas the TLR4-/- group conserved the p-NF-κB/NF- κB ratio contrasting with that found in TLR2-/-. We conclude: (i) TLRs are involved in renal I/R-induced cardiac hypertrophy; (ii) absence of TLRs prevents I/R-induced cardiac hypertrophy, despite renal lesions seeming to evolve towards those of chronic disease; (iii) TLR2 and TLR4 selectively regulate the systemic inflammatory profile and NF- κB activation. PMID:26448184

  13. O eletrocardiograma no diagnstico da hipertrofia ventricular de pacientes com doena renal crnica El electrocardiograma en el diagnstico de la hipertrofia ventricular de pacientes con enfermedad renal crnica Electrocardiography in the diagnosis of ventricular hypertrophy in patients with chronic renal disease

    Francisco de Assis Costa; Ivan Romero Rivera; Mirian Lira Castro de Vasconcelos; Andr Falco Pedrosa Costa; Rui Manoel dos Santos Pvoa; Maria Tereza Nogueira Bombig; Brulio Luna Filho; Valter Correia de Lima

    2009-01-01

    FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) um fator preditor independente de risco cardiovascular e sua caracterizao e prevalncia na doena renal crnica (DRC) carecem de melhor estudo. OBJETIVO: Estabelecer o diagnstico de HVE em pacientes com DRC em estgio 5 por seis diferentes critrios eletrocardiogrficos, correlacionando-os com o ndice de massa do ventrculo esquerdo (IMVE) obtido pelo ecocardiograma. MTODOS: Estudo transversal que incluiu 100 pacientes (58 homens e 4...

  14. Levosimendan prevents pressure-overload induced right ventricular failure

    Hillgaard, Thomas Krarup; Andersen, Asger; Andersen, Stine; Vildbrad, Mads Dam; Ringgaard, Steffen; Nielsen, Jan Mller; Nielsen-Kudsk, Jens Erik

    2015-01-01

    BACKGROUND: We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats. METHODS: Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated......, pressure-volume relations, gross anatomy and histology. RESULTS: PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by...... (VEH vs. REV 393 vs. 6610 mmHg p?0.05). CONCLUSION: Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure....

  15. Bone-marrow-derived CXCR4-positive tissue-committed stem cell recruitment in human right ventricular remodeling.

    Castellani, Chiara; Padalino, Massimo; China, Paolo; Fedrigo, Marny; Frescura, Carla; Milanesi, Ornella; Stellin, Giovanni; Thiene, Gaetano; Angelini, Annalisa

    2010-11-01

    The epicardium contributes to cardiac formation, particularly during embryogenesis. It remains to be seen if it is also involved in postnatal myocardial homeostasis. This study evaluates the topographic distribution of stem cells (c-Kit) and extracardiac progenitor cells (CXCR4+) and their contribution to ventricular remodeling in a model of pressure volume overload leading to right ventricle hypertrophy. Eleven specimens with hypoplastic left heart syndrome were evaluated and compared with 6 normal hearts from subjects matched for age and weight. All underwent Norwood procedure with the right ventricle becoming a systemic one, with pressure and volume overload leading to right ventricle remodeling. Transmural cardiac tissue samples from the right ventricle were analyzed by immunohistochemistry and morphometry. This is the first study to demonstrate that c-Kit-positive progenitor cells and tissue-committed stem cells (CXCR4+/CD45-) are higher in children with systemic right ventricle remodeling. We also show that the localization of cardiac progenitor and recruited CXCR4+ stem cells in the myocardium is site specific in hearts with right ventricle hypertrophy. These cells are mainly scattered in the interstitium of the epicardial layer. In contrast, myocyte proliferation is not a key process in right ventricular hypertrophy. Induced by the overexpression of SDF-1α by the myocardium, CXCR4 cell mobilization resembles SDF-1 homing factor distribution, showing transmural enhanced expression from the endocardium toward the epicardium. The study provides evidences of the site-specific epicardial localization of stem cells in a model of pressure/volume overload and suggests that the epicardium acts as a permissive niche in normal and pathologic conditions. PMID:20621330

  16. Postexertional Supraventricular Tachycardia in Children with Catecholaminergic Polymorphic Ventricular Tachycardia

    Else, Scott D. N.; Potts, James E.; Shubhayan Sanatani

    2012-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT) with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.

  17. TRPC channels are necessary mediators of pathologic cardiac hypertrophy.

    Wu, Xu; Eder, Petra; Chang, Baojun; Molkentin, Jeffery D

    2010-04-13

    Pathologic hypertrophy of the heart is regulated through membrane-bound receptors and intracellular signaling pathways that function, in part, by altering Ca(2+) handling and Ca(2+)-dependent signaling effectors. Transient receptor potential canonical (TRPC) channels are important mediators of Ca(2+)-dependent signal transduction that can sense stretch or activation of membrane-bound receptors. Here we generated cardiac-specific transgenic mice that express dominant-negative (dn) TRPC3, dnTRPC6, or dnTRPC4 toward blocking the activity of the TRPC3/6/7 or TRPC1/4/5 subfamily of channels in the heart. Remarkably, all three dn transgenic strategies attenuated the cardiac hypertrophic response following either neuroendocrine agonist infusion or pressure-overload stimulation. dnTRPC transgenic mice also were partially protected from loss of cardiac functional performance following long-term pressure-overload stimulation. Importantly, adult myocytes isolated from hypertrophic WT hearts showed a unique Ca(2+) influx activity under store-depleted conditions that was not observed in myocytes from hypertrophied dnTRPC3, dnTRPC6, or dnTRPC4 hearts. Moreover, dnTRPC4 inhibited the activity of the TRPC3/6/7 subfamily in the heart, suggesting that these two subfamilies function in coordinated complexes. Mechanistically, inhibition of TRPC channels in transgenic mice or in cultured neonatal myocytes significantly reduced activity in the calcineurin-nuclear factor of activated T cells (NFAT), a known Ca(2+)-dependent hypertrophy-inducing pathway. Thus, TRPC channels are necessary mediators of pathologic cardiac hypertrophy, in part through a calcineurin-NFAT signaling pathway. PMID:20351294

  18. Pak1 Is Required to Maintain Ventricular Ca2+ Homeostasis and Electrophysiological Stability through SERCA2a Regulation in Mice

    Wang, Yanwen; Tsui, Hoyee; Ke, Yunbo; Shi, Ying; Li, Yatong; Davies, Laura; Cartwright, Elizabeth J.; Venetucci, Luigi; Zhang, Henggui; Terrar, Derek A.; Huang, Christopher L-H.; John Solaro, R.; Wang, Xin; Lei, Ming

    2014-01-01

    Background Impaired sarcoplasmic reticular (SR) Ca2+ uptake resulting from decreased SR Ca2+-ATPase type 2a (SERCA2a) expression or activity is characteristic of heart failure (HF) with its associated ventricular arrhythmias. Recent attempts at gene therapy of these conditions explored strategies enhancing SERCA2a expression and/or activity as novel approaches to HF management. We here explore the role of Pak1 in maintaining ventricular Ca2+ homeostasis and electrophysiological stability under both normal physiological, and acute and chronic β-adrenergic stress conditions. Methods and Results Mice with a cardiomyocyte-specific Pak1 deletion (Pak1cko), but not controls (Pak1f/f), showed high incidences of ventricular arrhythmias and electrophysiological instability during either acute β-adrenergic or chronic β-adrenergic stress leading to hypertrophy, induced by isoproterenol. Isolated Pak1cko ventricular myocytes correspondingly showed aberrant cellular Ca2+ homeostasis. Pak1cko hearts showed an associated impairment of SERCA2a function and down-regulation of SERCA2a mRNA and protein expression. Further explorations of the mechanisms underlying the altered transcriptional regulation demonstrated that exposure to control Ad-shC2 virus infection increased SERCA2a protein and mRNA levels following phenylephrine stress in cultured neonatal rat cardiomyocytes (NRCMs). This was abolished by the Pak1-knockdown in Ad-shPak1-infected NRCMs and increased by constitutive over-expression of active Pak1 (Ad-CAPak1). We then implicated activation of serum response factor (SRF), a transcriptional factor well-known for its vital role in regulation of cardiogenesis genes in the Pak1-dependent regulation of SERCA2a. Conclusions These findings indicate that Pak1 is required to maintain ventricular Ca2+ homeostasis and electrophysiological stability and implicate Pak1 as a novel regulator of cardiac SERCA2a through a transcriptional mechanism. PMID:25217043

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

    Strom, C.C.; Kruhoffer, M.; Knudsen, Steen; Stensgaard-Hansen, F.; Jonassen, T.E.N.; Omtoft, T.F.; Haunso, S.; Sheikh, S.P.

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic...... gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in...... hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61...

  20. Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy

    Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

  1. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  2. Heart-Healthy Hypertrophy

    Trivedi, Chinmay M.; Epstein, Jonathan A

    2011-01-01

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

  3. Beat‐to‐Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study

    Waks, Jonathan W.; Soliman, Elsayed Z.; Henrikson, Charles A.; Sotoodehnia, Nona; Han, Lichy; Agarwal, Sunil K; Arking, Dan E.; Siscovick, David S; SOLOMON, Scott D.; Post, Wendy S; JOSEPHSON, MARK E.; Coresh, Josef; Tereshchenko, Larisa G.

    2015-01-01

    Background: Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results: Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hyp...

  4. Beat‐to‐Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study

    Waks, Jonathan W.; Soliman, Elsayed Z.; Henrikson, Charles A.; Sotoodehnia, Nona; Han, Lichy; Agarwal, Sunil K; Arking, Dan E.; Siscovick, David S; SOLOMON, Scott D.; Post, Wendy S; JOSEPHSON, MARK E.; Coresh, Josef; Tereshchenko, Larisa G.

    2015-01-01

    Background Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hyper...

  5. Inhibition of Receptor Interacting Protein Kinases Attenuates Cardiomyocyte Hypertrophy Induced by Palmitic Acid

    Zhao, Mingyue; Lu, Lihui; Lei, Song; Chai, Hua; Wu, Siyuan; Tang, Xiaoju; Bao, Qinxue; Chen, Li; Wu, Wenchao; Liu, Xiaojing

    2016-01-01

    Palmitic acid (PA) is known to cause cardiomyocyte dysfunction. Cardiac hypertrophy is one of the important pathological features of PA-induced lipotoxicity, but the mechanism by which PA induces cardiomyocyte hypertrophy is still unclear. Therefore, our study was to test whether necroptosis, a receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3-) dependent programmed necrosis, was involved in the PA-induced cardiomyocyte hypertrophy. We used the PA-treated primary neonatal rat cardiac myocytes (NCMs) or H9c2 cells to study lipotoxicity. Our results demonstrated that cardiomyocyte hypertrophy was induced by PA treatment, determined by upregulation of hypertrophic marker genes and cell surface area enlargement. Upon PA treatment, the expression of RIPK1 and RIPK3 was increased. Pretreatment with the RIPK1 inhibitor necrostatin-1 (Nec-1), the PA-induced cardiomyocyte hypertrophy, was attenuated. Knockdown of RIPK1 or RIPK3 by siRNA suppressed the PA-induced myocardial hypertrophy. Moreover, a crosstalk between necroptosis and endoplasmic reticulum (ER) stress was observed in PA-treated cardiomyocytes. Inhibition of RIPK1 with Nec-1, phosphorylation level of AKT (Ser473), and mTOR (Ser2481) was significantly reduced in PA-treated cardiomyocytes. In conclusion, RIPKs-dependent necroptosis might be crucial in PA-induced myocardial hypertrophy. Activation of mTOR may mediate the effect of necroptosis in cardiomyocyte hypertrophy induced by PA.

  6. The lipid peroxidation product 4-hydroxy-trans-2-nonenal causes protein synthesis in cardiac myocytes via activated mTORC1-p70S6K-RPS6 signaling.

    Calamaras, Timothy D; Lee, Charlie; Lan, Fan; Ido, Yasuo; Siwik, Deborah A; Colucci, Wilson S

    2015-05-01

    Reactive oxygen species (ROS) are elevated in the heart in response to hemodynamic and metabolic stress and promote hypertrophic signaling. ROS also mediate the formation of lipid peroxidation-derived aldehydes that may promote myocardial hypertrophy. One lipid peroxidation by-product, 4-hydroxy-trans-2-nonenal (HNE), is a reactive aldehyde that covalently modifies proteins thereby altering their function. HNE adducts directly inhibit the activity of LKB1, a serine/threonine kinase involved in regulating cellular growth in part through its interaction with the AMP-activated protein kinase (AMPK), but whether this drives myocardial growth is unclear. We tested the hypothesis that HNE promotes myocardial protein synthesis and if this effect is associated with impaired LKB1-AMPK signaling. In adult rat ventricular cardiomyocytes, exposure to HNE (10 μM for 1h) caused HNE-LKB1 adduct formation and inhibited LKB1 activity. HNE inhibited the downstream kinase AMPK, increased hypertrophic mTOR-p70S6K-RPS6 signaling, and stimulated protein synthesis by 27.1 ± 3.5%. HNE also stimulated Erk1/2 signaling, which contributed to RPS6 activation but was not required for HNE-stimulated protein synthesis. HNE-stimulated RPS6 phosphorylation was completely blocked using the mTOR inhibitor rapamycin. To evaluate if LKB1 inhibition by itself could promote the hypertrophic signaling changes observed with HNE, LKB1 was depleted in adult rat ventricular myocytes using siRNA. LKB1 knockdown did not replicate the effect of HNE on hypertrophic signaling or affect HNE-stimulated RPS6 phosphorylation. Thus, in adult cardiac myocytes HNE stimulates protein synthesis by activation of mTORC1-p70S6K-RPS6 signaling most likely mediated by direct inhibition of AMPK. Because HNE in the myocardium is commonly increased by stimuli that cause pathologic hypertrophy, these findings suggest that therapies that prevent activation of mTORC1-p70S6K-RPS6 signaling may be of therapeutic value. PMID:25617592

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

    Karoulas Takis

    2007-03-01

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

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

    Efthimiadis, Georgios K; Giannakoulas, Georgios; Parcharidou, Despina G; Ziakas, Antonios G; Papadopoulos, Christodoulos E; Karoulas, Takis; Pliakos, Christodoulos; Parcharidis, Georgios

    2007-01-01

    Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM) was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM). PMID:17349063

  9. In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study

    Wachtell, Kristian; Gerdts, Eva; Palmieri, Vittorio; Olsen, Michael H; Nieminen, Markku S; Papademetriou, Vasilios; Boman, Kurt; Dahlf, Bjrn; Aurigemma, Gerard P; Rokkedal, Jens E; Devereux, Richard B

    2010-01-01

    Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive...

  10. Physiologic versus pathologic hypertrophy: endurance exercise and chronic pressure overload.

    Braun, L T

    1994-07-01

    Endurance exercise requires that the heart maintain a highly elevated cardiac output for an extended period of time, working against a slightly elevated afterload. Endurance athletes manifest a large ventricular volume, characterized on echocardiogram by an increased end-diastolic internal diameter and wall thickness. This article describes the structural, functional, and biochemical alterations in the heart as a result of the physiologic stress of exercise, along with the signaling mechanisms for these changes. The article also compares exercise-induced hypertrophy and hypertrophy from chronic pressure overload. PMID:7931464

  11. Effect of PPAR γ activators on hypertrophic cardiac myocytes in vitro

    Objective: To investigate the effects of peroxisome proliferator-activated receptor γ (PPAR γ) activators pioglitazone and 15-deoxy-Δ12,14 prostaglandin J2(15d-PGJ2) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ2, two kinds of PPAR γ activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR γ activators inhibit hypertrophy of cardiac myocytes and PPAR γ-dependent pathway be involved in the inhibitory course

  12. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz; Nagle, Shea A; Treat, Jacqueline A; Cordeiro, Jonathan M

    2016-01-01

    cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... electrodes. Application of NS3623 to coronary-perfused left ventricular wedges resulted in increased phase 1 magnitude, epicardial AP notch and J wave amplitude. Patch clamp measurements of IKr and Ito revealed an increase in the magnitude of both currents. Culturing of Mid ventricular cells resulted in a...

  13. Effects of beta-blocker on left ventricular remodeling in rats with volume overload cardiac failure.

    Kobayashi, Masayuki; Machida, Noboru; Tanaka, Ryou; Yamane, Yoshihisa

    2008-11-01

    The beneficial effects of beta-blockers on left ventricular (LV) remodeling have been reported in association with several conditions that cause heart failure, but their effects on the volume overloaded heart failure have not been well defined. Fifty Wistar rats that survived aortocaval (AC) shunt creation were randomly allotted into the following two groups: untreated animals (ACS; n=26) and animals treated with 100 mg/kg/day metoprolol (MP; ACS+MP; n=24). The effects of MP were evaluated at 1, 4 and 12 weeks post-surgery through echocardiographic, hemodynamic and pathologic studies. At 12 weeks post-surgery, LV wall thinning associated with chamber dilatation was observed in ACS but not in ACS+MP. LV end-diastolic pressure and diastolic wall stress were lower in ACS+MP than in ACS. The increase in LV weight was similar in both ACS and ACS+MP at 1 and 4 weeks post-surgery, but at 12 weeks post-surgery, it was significantly greater in ACS+MP than in ACS. At the cellular level, although the cardiac myocyte length progressively increased to a similar extent in both groups, the mean cross-sectional diameter of these cells in ACS+MP was greater than in ACS. In conclusion, MP did not prevent early eccentric hypertrophy in response to volume overload. However, in the late phase of volume overload-induced heart failure, MP appears to allow for myocyte cross-sectional growth and thus prevents LV wall thinning, resulting in a net increase in LV mass. In this manner, MP might contribute to reduction of diastolic wall stress and thereby delay progression of heart failure. PMID:19057143

  14. MicroRNA Induced Cardiac Reprogramming In Vivo: Evidence for Mature Cardiac Myocytes and Improved Cardiac Function

    Jayawardena, Tilanthi M.; Finch, Elizabeth A.; Zhang, Lunan; Zhang, Hengtao; Hodgkinson, Conrad P.; Pratt, Richard E.; Rosenberg, Paul B.; Mirotsou, Maria; Dzau, Victor J.

    2014-01-01

    Rationale A major goal for the treatment of heart tissue damaged by cardiac injury is to develop strategies for restoring healthy heart muscle through the regeneration and repair of damaged myocardium. We recently demonstrated that administration of a specific combination of micro-RNAs (miR combo) into the infarcted myocardium leads to direct in vivo reprogramming of non-cardiac myocytes to cardiac myocytes. However, the biologic and functional consequences of such reprogramming are not yet known. Objective The aim of this study was to determine whether non-cardiac myocytes directly reprogrammed using miRNAs in vivo develop into mature functional cardiac myocytes in situ, and whether reprogramming leads to improvement of cardiac function. Methods and Results We subjected FSP1-Cre mice/tdTomato mice to cardiac injury by permanent ligation of the left anterior descending coronary artery (LAD) and injected lentiviruses encoding miR combo or a control nontargeting miRNA. miR combo significantly increased the number of reprogramming events in vivo. Five-to-six weeks following injury, morphological and physiological properties of tdTomato− and tdTomato+ cardiac myocyte-like cells were analyzed ex vivo. tdTomato+ cells expressed cardiac myocyte markers, sarcomeric organization, excitation-contraction coupling, and action potentials characteristic of mature ventricular cardiac myocytes (tdTomato− cells). Reprogramming was associated with improvement of cardiac function, as analyzed by serial echocardiography. There was a time delayed and progressive improvement in fractional shortening and other measures of ventricular function, indicating that miR combo promotes functional recovery of damaged myocardium. Conclusions The findings from this study further validate the potential utility of miRNA-mediated reprogramming as a therapeutic approach to promote cardiac regeneration following myocardial injury. PMID:25351576

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

    Erling David Kaunang

    2014-09-01

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

  16. Phosphoproteomic profiling of the myocyte.

    Edwards, Alistair V G; Cordwell, Stuart J; White, Melanie Y

    2011-10-01

    Protein phosphorylation underpins major cellular processes including energy metabolism, signal transduction, excitation-contraction coupling, apoptosis, and cell survival mechanisms and is thus critical to the myocyte. Targeted approaches, whereby a handful of phosphoproteins are investigated, can suffer from a relatively narrow view of cellular phosphorylation. In contrast, recent technical advances have allowed for the comprehensive documentation of phosphorylation events in complex biological environments, providing a deeper view of the "phosphoproteome." A global, high-throughput characterization of the myocardial phosphoproteome, however, has not yet been achieved. Efficient analysis of phosphorylated proteins and their roles in a dynamic cellular environment requires high-resolution strategies that can identify, localize, and quantify many thousands of phosphorylation sites in a single experiment. Such an approach requires specific enrichment and purification techniques, developed to align with high-end instrumentation for analysis. Cutting-edge phosphoproteomics is no longer restricted to gel-based technology, instead focusing on affinity enrichment prior to liquid chromatography and mass spectrometry. We will describe the best current methods and how they can be applied, as well as the challenges associated with them. We also present current phosphoproteomic investigations in the myocyte and its subcompartments. Although the techniques and instrumentation required to achieve the goal of a myocardial phosphoprotein catalog in physiological and diseased states are highly specialized, the potential biological insight provided by such an approach makes phosphoproteomics an important new avenue of investigation for the cardiovascular researcher. PMID:22010164

  17. Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges

    Pinamonti, Bruno; Brun, Francesca; Mestroni, Luisa; Sinagra, Gianfranco

    2014-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular (RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involv...

  18. Ventricular Scars and Ventricular Tachycardia

    Stevenson, William G.

    2009-01-01

    Ventricular tachycardia (VT) is a life-threatening arrhythmia that is common to all forms of heart disease and an important cause of sudden death. Ventricular scars from infarction or replacement fibrosis provide a substrate for reentry that is a common cause. Understanding the pathophysiologic link between ventricular scars and ventricular tachycardia informs approaches to identify patients at risk, has led to development of methods to ablate the arrhythmia substrate that can be applied even...

  19. Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations

    DanutaSzczesna-Cordary

    2014-01-01

    Cardiac hypertrophy represents one of the most important cardiovascular problems yet the mechanisms responsible for hypertrophic remodeling of the heart are poorly understood. In this report we aimed to explore the molecular pathways leading to two different phenotypes of cardiac hypertrophy in transgenic mice carrying mutations in the human ventricular myosin essential light chain (ELC). Mutation-induced alterations in the heart structure and function were studied in two transgenic (Tg) mous...

  20. Adenotonsillar hypertrophy and cor pulmonale: clinical and echocardiographic correlation.

    Kumar, E B; Jaggarao, N S

    1989-01-01

    It is well recognized that upper airways obstruction by adenotonsillar hypertrophy can lead to cor pulmonale, but delays in diagnosis still occur, leading to an appreciable morbidity and even occasional mortality. In the case presented, echocardiographic recognition of right ventricular enlargement and abnormal pulmonary valve motion served to complement and confirm the clinical diagnosis. Following surgical relief of the airways obstruction, the echocardiographic examination usefully documen...

  1. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    Torii, Yukio (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-09-01

    I studied experimentally the myocardial uptake of /sup 201/Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that /sup 201/Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia.

  2. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    I studied experimentally the myocardial uptake of 201Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that 201Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia. (J.P.N.)

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

    Søren P. Sheikh

    2006-04-01

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

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

    Strøm, Claes C.; Kruhøffer, Mogens; Knudsen, Steen; Stensgaard-Hansen, Frank; Jonassen, Thomas E. N.; Ørntoft, Torben F.; Haunsø, Stig

    2004-01-01

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat PMID:18629135

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

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

  6. The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy

    Mohamed, Tamer M. A.; Abou-Leisa, Riham; Stafford, Nicholas; Maqsood, Arfa; Zi, Min; Prehar, Sukhpal; Baudoin-Stanley, Florence; Wang, Xin; Neyses, Ludwig; Cartwright, Elizabeth J.; Oceandy, Delvac

    2016-01-01

    The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out Pmca4 specifically in cardiomyocytes does not produce this effect. Mechanistically, cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes. Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a therapeutic approach to treat this condition. PMID:27020607

  7. MRP4 and CFTR in the regulation of cAMP and β-adrenergic contraction in cardiac myocytes.

    Sellers, Zachary M; Naren, Anjaparavanda P; Xiang, Yang; Best, Philip M

    2012-04-15

    Spatiotemporal regulation of cAMP in cardiac myocytes is integral to regulating the diverse functions downstream of β-adrenergic stimulation. The activities of cAMP phosphodiesterases modulate critical and well-studied cellular processes. Recently, in epithelial and smooth muscle cells, it was found that the multi-drug resistant protein 4 (MRP4) acts as a cAMP efflux pump to regulate intracellular cAMP levels and alter effector function, including activation of the cAMP-stimulated Cl(-) channel, CFTR (cystic fibrosis transmembrane conductance regulator). In the current study we investigated the potential role of MRP4 in regulating intracellular cAMP and β-adrenergic stimulated contraction rate in cardiac myocytes. Cultured neonatal ventricular myocytes were used for all experiments. In addition to wildtype mice, β(1)-, β(2)-, and β(1)/β(2)-adrenoceptor, and CFTR knockout mice were used. MRP4 expression was probed via Western blot, intracellular cAMP was measured by fluorescence resonance energy transfer, while the functional role of MRP4 was assayed via monitoring of isoproterenol-stimulated contraction rate. We found that MRP4 is expressed in mouse neonatal ventricular myocytes. A pharmacological inhibitor of MRP4, MK571, potentiated submaximal isoproterenol-stimulated cAMP accumulation and cardiomyocyte contraction rate via β(1)-adrenoceptors. CFTR expression was critical for submaximal isoproterenol-stimulated contraction rate. Interestingly, MRP4-dependent changes in contraction rate were CFTR-dependent, however, PDE4-dependent potentiation of contraction rate was CFTR-independent. We have shown, for the first time, a role for MRP4 in the regulation of cAMP in cardiac myocytes and involvement of CFTR in β-adrenergic stimulated contraction. Together with phosphodiesterases, MRP4 must be considered when examining cAMP regulation in cardiac myocytes. PMID:22381067

  8. The effects of tubulin-binding agents on stretch-induced ventricular arrhythmias.

    Parker, K K; Taylor, L K; Atkinson, J B; Hansen, D E; Wikswo, J P; Atkinson, B

    2001-04-01

    Stretch-activated ion channels have been identified as transducers of mechanoelectric coupling in the heart, where they may play a role in arrhythmogenesis. The role of the cytoskeleton in ion channel control has been a topic of recent study and the transmission of mechanical stresses to stretch-activated channels by cytoskeletal attachment has been hypothesized. We studied the arrhythmogenic effects of stretch in 16 Langendorff-perfused rabbit hearts in which we pharmacologically manipulated the microtubular network of the cardiac myocytes. Group 1 (n=5) was treated with colchicine, which depolymerizes microtubules, and Group 2 (n=6) was treated with taxol, which polymerizes microtubules. Stretch-induced arrhythmias were produced by transiently increasing the volume of a fluid-filled left ventricular balloon with a volume pump driven by a computer-controlled stepper motor. Electrical events were recorded by a contact electrode which provided high-fidelity recordings of monophasic action potentials and stretch-induced depolarizations. The probability of eliciting a stretch-induced arrhythmia increased (0.22+/-0.11 to 0.62+/-0.19, p=0.001) in hearts treated with taxol (5 microM), whereas hearts treated with colchicine (100 microM) showed no statistically significant change. We conclude that proliferation of microtubules increased the arrhythmogenic effect of transient left ventricle diastolic stretch. This result indicates a possible mode of arrhythmogenesis in chemotherapeutic patients and patients exhibiting uncompensated ventricular hypertrophy. The data would indicate that the cytoskeleton represents a possible target for antiarrhythmic therapies. PMID:11301068

  9. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

  10. Physiologic and pathologic myocardial hypertrophy--physiologic and pathologic regression of hypertrophy?

    Simko, F

    2002-01-01

    Hypertrophy of the left ventricle is an adaptive phenomenon of ambiguous biological value. It enables improvement of the heart performance without substantial enhancement of energetic demands. On the other hand, pathologic left ventricular hypertrophy (LVH) is characterized by increased fibrosis, diminished coronary flow reserve and protein remodeling, resulting in increased cardiovascular morbidity and mortality. Achievement of LVH regression is thus considered a principal therapeutic aim. However, the reversal of LVH is a very complex process in which both hemodynamic and non-hemodynamic alterations participate. Reversal of LVH does not mean the re-expression of the original genotype and normalization of myocardial structure and function. It does not guarantee that the heart will be normal in all aspects. Regression of hypertrophy induced by different therapeutic means may exhibit different properties and patterns, with variable biological implications. Physiologic growth stimulators seem to induce LVH without prognostically undesirable alterations. It is a challenge to determine which approach to treatment of hemodynamic overload and concomitant LVH is optimal. PMID:11863392

  11. Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes.

    He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

    2014-01-01

    Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

  12. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    Olsen, M H; Hjerkinn, E; Wachtell, K; Høieggen, A; Bella, J N; Nesbitt, S D; Fossum, E; Kjeldsen, S E; Julius, S; Ibsen, H

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients...... with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by...

  13. Diagnostic imaging of cardiac hypertrophy

    As imaging techniques for cardiac hypertrophy, the ultrasonic dimension gauze technique, echocardiography, ventriculography and the RI technique including emission RI tomography were outlined. (Chiba, N.)

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

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

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

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

    2010-01-01

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

  16. Liganded Peroxisome Proliferator-Activated Receptors (PPARs) Preserve Nuclear Histone Deacetylase 5 Levels in Endothelin-Treated Sprague-Dawley Rat Cardiac Myocytes

    Zhang, Haining; Shao, Zongjun; Alibin, Caroline P.; Acosta, Crystal; Anderson, Hope D

    2014-01-01

    Ligand activation of peroxisome proliferator-activated receptors (PPARs) prevents cardiac myocyte hypertrophy, and we previously reported that diacylglycerol kinase zeta (DGKζ) is critically involved. DGKζ is an intracellular lipid kinase that catalyzes phosphorylation of diacylglycerol; by attenuating DAG signaling, DGKζ suppresses protein kinase C (PKC) and G-protein signaling. Here, we investigated how PPAR-DGKζ signaling blocks activation of the hypertrophic gene program. We focused on ex...

  17. On the origin of pain in patients with stable essential hypertension and asymmetrical myocardial hypertrophy

    A study of 230 patients with essential hypertension, stage 2B, asymmetrical myocardial hypertrophy and chest pains has suggested that the pain syndrome, presenting as ''possible angina'', positive functional tests and reduced label accumulation around the ventricular septum may be indicative of coronary insufficiency

  18. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Zaugg, Christian E.

    2004-01-01

    Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF) are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocar...

  19. Krüppel-like factor 4 regulates pressure-induced cardiac hypertrophy

    Liao, Xudong; Haldar, Saptarsi M; Lu, Yuan; Jeyaraj, Darwin; Paruchuri, Kaavya; Nahori, Monika; Cui, Yingjie; Kaestner, Klaus H; Jain, Mukesh K.

    2010-01-01

    Krüppel-like factors (KLF) are a subfamily of the zinc-finger class of transcriptional regulators that play important roles in diverse cellular processes. While a number of KLFs are expressed in cardiomyocytes, little is known about their specific roles in the heart in vivo. Here, we demonstrate that KLF4 is induced by hypertrophic stimuli in cultured cardiomyocytes and in the mouse heart. Overexpression of KLF4 in neonatal rat ventricular myocytes inhibits three cardinal features of cardiomy...

  20. Mouse models for the study of postnatal cardiac hypertrophy

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  1. Calcium handling by vascular myocytes in hypertension

    R.C.A. Tostes

    1997-03-01

    Full Text Available Calcium ions (Ca2+ trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1 the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2 Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3 intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4 using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

  2. Impact of arterial hypertension on the status of left ventricular myocardium: thallium-201 myocardial scintigraphic findings

    Functional relationships was examined between the parameters of myocardial perfusion, left ventricular myocardial mass, and complications developed in patients with coronary heart diseases concominant with arterial hypertension. As perfusion deficiency progressed, the patients with complicated natural history of arterial hypertension were found to increase in number with higher left ventricular myocardial mass index. In patients with arterial hypertension, the critical hypertrophy phase in which the index of left ventricular myocardial mass was 110-120 gm2 was demonstrated to be followed by myocardial perfusion deficiency. If the myocardial mass index is 90 g/m2, it means a phase of compensatory hypertrophy, which shows higher myocardial perfusion

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

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

  4. Heterogeneous myocyte enhancer factor-2 (Mef2) activation in myocytes predicts focal scarring in hypertrophic cardiomyopathy

    Konno, Tetsuo; Chen, Dan; Wang, Libin; Wakimoto, Hiroko; Teekakirikul, Polakit; Nayor, Matthew; Kawana, Masataka; Eminaga, Seda; Gorham, Joshua M.; Pandya, Kumar; Smithies, Oliver; Naya, Francisco J.; Eric N. Olson; Seidman, J.G.; Seidman, Christine E.

    2010-01-01

    Unknown molecular responses to sarcomere protein gene mutations account for pathologic remodeling in hypertrophic cardiomyopathy (HCM), producing myocyte growth and increased cardiac fibrosis. To determine if hypertrophic signals activated myocyte enhancer factor-2 (Mef2), we studied mice carrying the HCM mutation, myosin heavy-chain Arg403Gln, (MHC403/+) and an Mef2-dependent β-galactosidase reporter transgene. In young, prehypertrophic MHC403/+ mice the reporter was not activated. In hypert...

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

    Cristian Aguilar

    2011-06-01

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

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

    Gerdts, E.; Okin, P.M.; Simone, G. de; Cramariuc, D.; Wachtell, K.; Boman, K.; Devereux, R.B.

    2008-01-01

    In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point...... occurred were assessed in 863 hypertensive patients with electrocardiographic left ventricular hypertrophy aged 55 to 80 years (mean: 66 years) during 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Echocardiography substudy....... Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height(2.7) >or=46.7 g/m(2.7) and 49.2 g/m(2.7) in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity...

  7. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  8. Compensative hypertrophy of the kidney

    Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient

  9. Regulation of Cardiac Hypertrophy: the nuclear option

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

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

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed IK1 channels is low enough. At too high an expression level of IK1 channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of IK1 channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of IK1 channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below ∼1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of IK1 has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations

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

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

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

    T. Fernandes

    2011-09-01

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

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

    Martins A.S.

    2001-01-01

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

  14. Prolactin induces adrenal hypertrophy

    Silva E.J.

    2004-01-01

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

  15. Cardiac mast cells regulate myocyte ANP release via histamine H2 receptor in beating rabbit atria.

    Li, Dan; Wen, Jin Fu; Jin, Jing Yu; Quan, He Xiu; Cho, Kyung Woo

    2009-06-01

    It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H(2) receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell-cardiomyocyte communication via the histamine-ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy. PMID:19328828

  16. Signal transduction and activator of transcription (STAT) protein-dependent activation of angiotensinogen promoter: A cellular signal for hypertrophy in cardiac muscle

    Mascareno, Eduardo; Dhar, Manya; M.A.Q. SIDDIQUI

    1998-01-01

    The role of the peptide hormone angiotensin (AngII) in promoting myocardial hypertrophy is well documented. Our studies demonstrate that AngII uses a signaling pathway in cardiac myocytes in which the promoter of the gene encoding its prohormone, angiotensinogen, serves as the target site for activated signal transduction and activator of transcription (STAT) proteins. Gel mobility-shift assay revealed that STAT3 and STAT6 are selectively activated by AngII treatment of cardiomyocytes in cult...

  17. Quality metrics for stem cell-derived cardiac myocytes

    Sheehy, SP; Pasqualini, F; Grosberg, A; Park, SJ; Aratyn-Schaus, Y; Parker, KK

    2014-01-01

    Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology research purposes. Although FDA-mandated quality assurance metrics address safety issues in the manufacture of stem cell-based products, no standardized guidelines currently exist for the evaluation of stem cell-derived myocyte functionality. As a result, it is unclear whether the various stem cell-derived myocyte cell lines on the...

  18. Quality Metrics for Stem Cell-Derived Cardiac Myocytes

    Sean P. Sheehy; Francesco Pasqualini; Anna Grosberg; Sung Jin Park; Yvonne Aratyn-Schaus; Kevin Kit Parker

    2014-01-01

    Summary Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology research purposes. Although FDA-mandated quality assurance metrics address safety issues in the manufacture of stem cell-based products, no standardized guidelines currently exist for the evaluation of stem cell-derived myocyte functionality. As a result, it is unclear whether the various stem cell-derived myocyte cell line...

  19. MicroRNA-1 Downregulation Increases Connexin 43 Displacement and Induces Ventricular Tachyarrhythmias in Rodent Hypertrophic Hearts

    Curcio, A.; Torella, D; C. Iaconetti; E. Pasceri; J. Sabatino; Sorrentino, S.; S. Giampà; M. Micieli; Polimeni, A.; B. Henning; de Leone, A; D. Catalucci; Ellison, G; Condorelli, G.; C. Indolfi

    2013-01-01

    Downregulation of the muscle-specific microRNA-1 (miR-1) mediates the induction of pathologic cardiac hypertrophy. Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT). However, it is still unknown whether miR-1 and Cx43 are interconnected in the pro-arrhythmic context of hypertrophy. Thus, in this study we investigated whether a reduction in the extent of cardiac hypertrophy could limit ...

  20. Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling.

    Gitau, Samuel Chege; Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Liang, Haihai; Qian, Ming; Lv, Lifang; Li, Tianshi; Xu, Bozhi; Wang, Zhiguo; Zhang, Yong; Xu, Chaoqian; Lu, Yanjie; Du, Zhiming; Shan, Hongli; Yang, Baofeng

    2015-12-01

    Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mgkg(-1)d(-1)); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmolL(-1)) was treated with the human equivalent of low (10 or 100 ?molL(-1)) and high (1000 ?molL(-1)) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, ?-myosin heavy chain (?-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of ?-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3?. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of ?-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin. PMID:26626190

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

    Xiao-xing ZHU

    2011-07-01

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

  2. Mitochondria in cardiac hypertrophy and heart failure

    Rosca, Mariana G.; TANDLER, BERNARD; Hoppel, Charles L

    2012-01-01

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

  3. Arrhythmogenic Right Ventricular Dysplasia

    MENU Return to Web version Arrhythmogenic Right Ventricular Dysplasia Overview What is arrhythmogenic right ventricular dysplasia? Arrhythmogenic right ventricular dysplasia (say: “uh-rith-mo-jen-ic right ven-trick- ...

  4. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and

  5. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  6. The thickened left ventricle: etiology, differential diagnosis and implications for cardiovascular radiology; Der dicke linke Ventrikel. Ursachen und Differenzialdiagnose der linksventrikulaeren Hypertrophie und Implikationen fuer die kardiovaskulaere Radiologie

    Bischoff, P.; Barkhausen, J.; Hunold, P. [Universitaetsklinikum Schleswig-Holstein, Luebeck (Germany). Klinik fuer Radiologie und Nuklearmedizin; Radke, P.W. [Universitaetsklinikum Schleswig Holstein, Luebeck (Germany). Medizinische Klinik II

    2012-08-15

    Hypertrophy of the left ventricular myocardium is a common finding and can be reliably detected by echocardiography, CT and MRI. Common causes include diseases associated with increased cardiac afterload as well as primary and secondary cardiomyopathy. With the opportunity to determine functional parameters and myocardial mass precisely as well as to detect structural changes of the cardiac muscle simultaneously, cardiac MRI is the most precise imaging method for quantifying left ventricular hypertrophy as well as determining the cause and the exact characterization of the myocardial changes. It is mandatory, however, to create a flexible, individually adapted examination protocol. This review presents useful diagnostic algorithms in relation to different underlying pathologies in patients with left ventricular hypertrophy. (orig.)

  7. Pathologic hypertrophy with fibrosis: the structural basis for myocardial failure.

    Weber, K T; Brilla, C G; Campbell, S E; Zhou, G; Matsubara, L; Guarda, E

    1992-08-01

    The major risk factor associated with the appearance of adverse cardiovascular events and outcome attributable to cardiovascular disease is left ventricular hypertrophy (LVH). Why this should be so resides not in the increase in myocardial mass per se, but in the disruption of myocardial structure. An abnormal accumulation of fibrillar collagen within the adventitia of intramyocardial coronary arteries and neighboring interstitial spaces represents such a distortion in structure. Furthermore, this fibrosis disrupts the electrical and mechanical behavior of the hypertrophied myocardium. Mechanisms responsible for fibrillar collagen accumulation have been examined in intact animals and cultured cardiac fibroblasts. In vivo studies indicate that myocardial fibrosis is associated with the presence of chronic mineralocorticoid excess, relative to sodium intake and excretion, not hemodynamic workload. Accordingly, fibrosis can appear in both the hypertensive, hypertrophied and nonhypertensive, nonhypertrophied ventricles. In both primary and secondary hyperaldosteronism it was possible to prevent myocardial fibrosis with an aldosterone receptor antagonist, while in unilateral renal ischemia angiotensin converting enzyme (ACE) inhibition was similarly cardioprotective. A regression in fibrous tissue and normalization of diastolic stiffness has also been possible using ACE inhibition, bringing forward the concept of cardioreparation and the notion that heart failure due to fibrosis may be reversible. In vitro studies indicate that effector hormones of the renin-angiotensin-aldosterone system stimulate fibroblast collagen synthesis. Aldosterone, in pathophysiologic concentrations, and angiotensin II, in much larger concentrations, each enhance collagen synthesis without altering the mitogenic potential of these cells. Thus, elevations in circulating aldosterone and angiotensin II, relative to sodium intake, have the potential to not only alter sodium homeostasis and vascular tonicity, but also the structure of cardiovascular tissue. Thus, myocardial fibrosis represents a structural basis for pathologic hypertrophy and ultimately accounts for the appearance of adverse cardiovascular events and outcomes. PMID:1366263

  8. Myocardial remodeling and pathologic hypertrophy.

    Weber, K T; Brilla, C G; Janicki, J S

    1991-04-15

    The hallmark of myocardial hypertrophy associated with congestive failure is interstitial fibrosis. How does the fibrosis develop, and what can be done about it? Hormonal and hemodynamic factors are examined. Experimental studies with ACE inhibitors or aldosterone receptor antagonists suggest that the fibrosis may be prevented or reversed. PMID:2010482

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

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

    2011-01-01

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

  10. Myomaker mediates fusion of fast myocytes in zebrafish embryos

    Landemaine, Aurlie; Rescan, Pierre-Yves; Gabillard, Jean-Charles, E-mail: Jean-charles.gabillard@rennes.inra.fr

    2014-09-05

    Highlights: Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. Myomaker is essential for fast myocyte fusion in zebrafish. The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi.

  11. Myomaker mediates fusion of fast myocytes in zebrafish embryos

    Highlights: Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. Myomaker is essential for fast myocyte fusion in zebrafish. The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi

  12. Modeling beta-adrenergic control of cardiac myocyte contractility in silico

    Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

  13. Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

    Weckstrm Matti

    2009-08-01

    Full Text Available Abstract Background The cardiomyocyte is a prime example of inherently complex biological system with inter- and cross-connected feedback loops in signalling, forming the basic properties of intracellular homeostasis. Functional properties of cells and tissues have been studied e.g. with powerful tools of genetic engineering, combined with extensive experimentation. While this approach provides accurate information about the physiology at the endpoint, complementary methods, such as mathematical modelling, can provide more detailed information about the processes that have lead to the endpoint phenotype. Results In order to gain novel mechanistic information of the excitation-contraction coupling in normal myocytes and to analyze sophisticated genetically engineered heart models, we have built a mathematical model of a mouse ventricular myocyte. In addition to the fundamental components of membrane excitation, calcium signalling and contraction, our integrated model includes the calcium-calmodulin-dependent enzyme cascade and the regulation it imposes on the proteins involved in excitation-contraction coupling. With the model, we investigate the effects of three genetic modifications that interfere with calcium signalling: 1 ablation of phospholamban, 2 disruption of the regulation of L-type calcium channels by calcium-calmodulin-dependent kinase II (CaMK and 3 overexpression of CaMK. We show that the key features of the experimental phenotypes involve physiological compensatory and autoregulatory mechanisms that bring the system to a state closer to the original wild-type phenotype in all transgenic models. A drastic phenotype was found when the genetic modification disrupts the regulatory signalling system itself, i.e. the CaMK overexpression model. Conclusion The novel features of the presented cardiomyocyte model enable accurate description of excitation-contraction coupling. The model is thus an applicable tool for further studies of both normal and defective cellular physiology. We propose that integrative modelling as in the present work is a valuable complement to experiments in understanding the causality within complex biological systems such as cardiac myocytes.

  14. PGC-1α accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    Energy metabolism and Ca2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1α in cardiac Ca2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca2+ transients, suggesting that myofilament sensitivity to Ca2+ increased. Interestingly, the decay kinetics of global Ca2+ transients and Ca2+ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), but not Na+/Ca2+ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca2+ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca2+ homeostasis, because SR Ca2+ load and the propensity for Ca2+ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.

  15. Echocardiographic assessment of the different left ventricular geometric patterns in hypertensive patients

    Delma Maria Cunha

    2001-01-01

    Full Text Available OBJECTIVE: To identiy left ventricular geometric patterns in hypertensive patients on echocardiography, and to correlate those patterns with casual blood pressure measurements and with the parameters obtained on a 24-hour ambulatory blood pressure monitoring. METHODS: We studied sixty hypertensive patients, grouped according to the Joint National Committee stages of hypertension.. Using the single- and two-dimensional Doppler Echocardiography, we analyzed the left ventricular mass and the geometric patterns through the correlation of left ventricular mass index and relative wall thickness. On ambulatory blood pressure monitoring we assessed the means and pressure loads in the different geometric patterns detected on echocardiography RESULTS: We identified three left ventricular geometric patterns: 1 concentric hypertrophy, in 25% of the patients; 2 concentric remodeling, in 25%; and 3 normal geometry, in 50%. Casual systolic blood pressure was higher in the group with concentric hypertrophy than in the other groups (p=0.001. Mean systolic pressure in the 24h, daytime and nighttime periods was also higher in patients with concentric hypertrophy, as compared to the other groups (p=0.003, p=0.004 and p=0.007. Daytime systolic load and nighttime diastolic load were higher in patients with concentric hypertrophy ( p=0.004 and p=0.01, respectively. CONCLUSIONS: Left ventricular geometric patterns show significant correlation with casual systolic blood pressure, and with means and pressure loads on ambulatory blood pressure monitoring.

  16. Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment.

    Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

    2016-01-01

    Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5mg/kg body weight compared to free Curcumin at 35mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, ?-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. PMID:26612707

  17. Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction.

    Porrello, Enzo R; Bell, James R; Schertzer, Jonathan D; Curl, Claire L; McMullen, Julie R; Mellor, Kimberley M; Ritchie, Rebecca H; Lynch, Gordon S; Harrap, Stephen B; Thomas, Walter G; Delbridge, Lea M D

    2009-03-01

    The identification of genetic factors influencing cardiac growth independently of increased load is crucial to an understanding of the molecular and cellular basis of pathological cardiac hypertrophy. The central aim of this investigation was to determine how pathological hypertrophy in the adult can be linked with disturbances in cardiomyocyte growth and viability in early neonatal development. The hypertrophic heart rat (HHR) model is derived from the spontaneously hypertensive rat and exhibits marked cardiac hypertrophy, in the absence of a pressure load at maturity. Hearts were harvested from male HHR, and control strain normal heart rats (NHR), at different stages of postnatal development [neonatal (P2), 4 wk, 6 wk, 8 wk, 12 wk, 20 wk]. Isolated neonatal cardiomyocytes were prepared to evaluate cell size, number, and binucleation. At postnatal day 2, HHR hearts were considerably smaller than control NHR (4.3 +/- 0.2 vs. 5.0 +/- 0.1 mg/g, P < 0.05). Cardiac growth restriction in the neonatal HHR was associated with reduced myocyte size (length and width) and an increased proportion of binucleated cardiomyocytes. Furthermore, the number of cardiomyocytes isolated from HHR neonatal hearts was significantly less ( approximately 29%) than NHR. We also observe that growth stress in the neonate is associated with accentuated PI3K and suppressed MAPK activation, although these signaling pathways are normalized in the adult heart exhibiting established hypertrophy. Thus, using the HHR model, we identified novel molecular and cellular mechanisms involving premature exit from the cell cycle, reduced cardiomyocyte endowment, and dysregulated trophic signaling during early development, which are implicated in the etiology of heritable cardiac hypertrophy in the adult. PMID:19129376

  18. Left ventricular dysfunction in normotensive Type 1 diabetic patients: the impact of autonomic neuropathy

    Taskiran, M; Rasmussen, Verner; Rasmussen, Bo Valdemar; Fritz-Hansen, T; Larsson, H. B. W.; Jensen, G. B.; Hilsted, J

    Aims The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy (AN) are largely unknown. The aim was to determine the relative role of AN in the pathogenesis of cardiac diastolic dysfunction and left ventricular hypertrophy in Type 1...... diabetes. Methods Ten Type 1 diabetic patients with AN, defined by cardiovascular tests (AN+) and 10 age- and sex-matched patients without neuropathy (AN-) as well as 10 healthy subjects (C) participated in the study. Left ventricular diastolic function was assessed by Doppler echocardiography, whilst...... showed a significantly greater left ventricular mass index in AN+ compared with C [103 +/- 4 g/m(2) (AN+) vs. 98 +/- 7 (AN-) and 92 +/- 4 g/m(2) (C), P < 0.05]. Conclusion Autonomic neuropathy is associated with left ventricular hypertrophy and diastolic dysfunction in Type 1 diabetic patients...

  19. : AMPK and skeletal muscle hypertrophy

    Mounier, Rémi; Lantier, Louise; Leclerc, Jocelyne; Sotiropoulos, Athanassia; Pende, Mario; Daegelen, Dominique; Sakamoto, Kei; Foretz, Marc; Viollet, Benoit

    2009-01-01

    Activation of AMP-activated protein kinase (AMPK) inhibits protein synthesis through the suppression of the mammalian target of rapamycin complex 1 (mTORC1), a critical regulator of muscle growth. The purpose of this investigation was to determine the role of the AMPKalpha1 catalytic subunit on muscle cell size control and adaptation to muscle hypertrophy. We found that AMPKalpha1(-/-) primary cultured myotubes and myofibers exhibit larger cell size compared with control cells in response to ...

  20. Allopurinol Benefits Left Ventricular Mass and Endothelial Dysfunction in Chronic Kidney Disease

    Kao, Michelle P.; Ang, Donald S.; Gandy, Stephen J.; Nadir, M. Adnan; Houston, J. Graeme; Lang, Chim C; Struthers, Allan D

    2011-01-01

    Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD a...

  1. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45Ca tracer measurements after loading the myocytes with 45Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect

  2. Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy A redução da pressão de perfusão coronariana está associada com a fibrose endocárdica no modelo de hipertrofia por sobrecarga de volume em ratos

    Maria Carolina Guido; Márcia Kiyomi Koike; Clovis de Carvalho Frimm

    2004-01-01

    Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To in...

  3. Advanced Anderson-Fabry disease presenting with left ventricular apical aneurysm and ventricular tachycardia.

    Poulin, Marie-France; Shah, Alap; Trohman, Richard G; Madias, Christopher

    2015-06-16

    A 54-year-old female with Anderson-Fabry disease (AFD)-R342Q missense mutation on exon 7 in alpha-galactosidase A (GLA) gene - presented with sustained ventricular tachycardia. Imaging confirmed the presence of a new left ventricular apical aneurysm (LVAA) and a significantly reduced intra-cavitary gradient compared to two years prior. AFDcv is an X-linked lysosomal storage disorder caused by GLA enzyme deficiency. The phenotypic expression of AFD in the heart is not well described. Cardiac involvement can include left ventricular hypertrophy (LVH), which is typically symmetric, but can also mimic hypertrophic cardiomyopathy (HCM). Left ventricular apical aneurysm is a rare finding in HCM. We suggest a shared mechanism of LVAA formation in AFD and HCM, independent of the underlying cardiomyopathy. Mechanisms of LVAA formation in HCM include genetic predisposition and long-standing left ventricular wall stress from elevated intra-cavitary systolic pressures due to mid-cavitary obstruction. Both mechanisms are supported in this patient (a brother with AFD also developed a small LVAA). Screening for AFD should be considered in cases of unexplained LVH, particularly in patients with the aneurysmal variant of HCM. PMID:26090373

  4. Masseter and medial pterygoid muscle hypertrophy

    R, Guruprasad; Rishi, Sudhirkumar; Nair, Preeti P; Thomas, Shaji

    2011-01-01

    Hypertrophy refers to an enlargement caused by an increase in the size but not in the number of cells. Generalised masticatory muscle hypertrophy may affect the temporalis muscle, masseters and medial pterygoids in a variety of combinations. Masseteric hypertrophy may present as either unilateral or bilateral painless swelling of unknown origin in the region of angle of mandible. It is a relatively rare condition and presents a diagnostic dilemma. While the history and clinical examination ar...

  5. Growth Arrest-Specific 6 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy.

    Zhao, Yi-Fan; Xu, Da-Chun; Zhu, Guo-Fu; Zhu, Meng-Yun; Tang, Kai; Li, Wei-Ming; Xu, Ya-Wei

    2016-01-01

    Growth arrest-specific 6 (GAS6) is a member of the vitamin K-dependent protein family that is involved in the regulation of the cardiovascular system, including vascular remodeling, homeostasis, and atherosclerosis. However, there is still no study that systemically elucidates the role of GAS6 in cardiac hypertrophy. Here, we found that GAS6 was upregulated in human dilated cardiomyopathic hearts, hypertrophic murine hearts, and angiotensin II-treated cardiomyocytes. Next, we examined the influence of GAS6 expression in response to a cardiac stress by inducing chronic pressure overload with aortic banding in wild-type and GAS6-knockout mice or cardiac-specific GAS6 overexpressing mice. Under basal conditions, the GAS6-knockout mice had normal left ventricular structure and function but after aortic banding, the mice demonstrated less hypertrophy, fibrosis, and contractile dysfunction when compared with wild-type mice. Conversely, cardiac-specific overexpression of GAS6 exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and dysfunction. Furthermore, we demonstrated that GAS6 activated the mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 pathway during pressure overload-induced cardiac hypertrophy, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed GAS6 overexpression-induced cardiac hypertrophy and fibrosis, resulting in improved cardiac function. Collectively, our data support the notion that GAS6 impairs ventricular adaptation to chronic pressure overload by activating mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 signaling. Our findings suggest that strategies to reduce GAS6 activity in cardiac tissue may be a novel approach to attenuate the development of congestive heart failure. PMID:26573712

  6. Ventricular torsional relation to ventricular fiber arrangement

    Ranjbar, Saeed; Meybodi, Mahmood Emami

    2014-01-01

    Left ventricular torsion from helically oriented myofibers is a key parameter of cardiac performance. Physicians observing heart motion on echocardiograms, during cardiac catheterization, or in the operating room, are impressed by the twisting or rotary motion of the left ventricle during systole. Conceptually, the heart has been treated as a pressure chamber. The rotary or torsional deformation has been poorly understood by basic scientists and has lacked clinical relevance. The aim of this paper attempts to discuss about this question: Is ventricular twisting related to ventricular fiber arrangement? That is dependent to an assumed model of the left ventricular structure.

  7. Cardiogenic shock accompanied by dynamic left ventricular outflow tract obstruction and myocardial bridging after transient complete atrioventricular block mimicking ST-elevation myocardial infarction: a case report

    Kang, Seonghui; An, Sanghee; Yu, Hyung Min; Kim, Jiwan; Kim, Sung Hea; Kim, Hyun-Joong; Chung, Sang Man

    2013-01-01

    Background Dynamic left ventricular outflow tract obstruction with or without mitral regurgitation is typically observed in hypertrophic cardiomyopathy, but is also occasionally seen without left ventricular hypertrophy. In this report, we present a case of cardiogenic shock that mimics ST-elevation myocardial infarction, due to dynamic left ventricular outflow tract obstruction with transient mitral regurgitation and myocardial bridging after transient complete atrioventricular block. Case p...

  8. Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy.

    Smith, Nicola J; Chan, Hsiu-Wen; Qian, Hongwei; Bourne, Allison M; Hannan, Katherine M; Warner, Fiona J; Ritchie, Rebecca H; Pearson, Richard B; Hannan, Ross D; Thomas, Walter G

    2011-05-01

    Major interest surrounds how angiotensin II triggers cardiac hypertrophy via epidermal growth factor receptor transactivation. G protein-mediated transduction, angiotensin type 1 receptor phosphorylation at tyrosine 319, and β-arrestin-dependent scaffolding have been suggested, yet the mechanism remains controversial. We examined these pathways in the most reductionist model of cardiomyocyte growth, neonatal ventricular cardiomyocytes. Analysis with [(32)P]-labeled cardiomyocytes, wild-type and [Y319A] angiotensin type 1 receptor immunoprecipitation and phosphorimaging, phosphopeptide analysis, and antiphosphotyrosine blotting provided no evidence for tyrosine phosphorylation at Y319 or indeed of the receptor, and mutation of Y319 (to A/F) did not prevent either epidermal growth factor receptor transactivation in COS-7 cells or cardiomyocyte hypertrophy. Instead, we demonstrate that transactivation and cardiomyocyte hypertrophy are completely abrogated by loss of G-protein coupling, whereas a constitutively active angiotensin type 1 receptor mutant was sufficient to trigger transactivation and growth in the absence of ligand. These results were supported by the failure of the β-arrestin-biased ligand SII angiotensin II to transactivate epidermal growth factor receptor or promote hypertrophy, whereas a β-arrestin-uncoupled receptor retained these properties. We also found angiotensin II-mediated cardiomyocyte hypertrophy to be attenuated by a disintegrin and metalloprotease inhibition. Thus, G-protein coupling, and not Y319 phosphorylation or β-arrestin scaffolding, is required for epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy via the angiotensin type 1 receptor. PMID:21383310

  9. Genetics Home Reference: myostatin-related muscle hypertrophy

    ... Health Conditions myostatin-related muscle hypertrophy myostatin-related muscle hypertrophy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body ...

  10. Cardiac myocyte exosomes: stability, HSP60, and proteomics

    Z.A. Malik; Kott, K. S.; Poe, A. J.; Kuo, T.; Chen, L.; Ferrara, K W; Knowlton, A A

    2013-01-01

    Exosomes, which are 50- to 100-nm-diameter lipid vesicles, have been implicated in intercellular communication, including transmitting malignancy, and as a way for viral particles to evade detection while spreading to new cells. Previously, we demonstrated that adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. Thus, release of HSP60 from exosomes would b...

  11. Renal dysfunction, restrictive left ventricular filling pattern and mortality risk in patients admitted with heart failure

    Schou, Morten; Kjaergaard, Jesper; Torp-Pedersen, Christian; Hassager, Christian; Gustafsson, Finn; Akkan, Dilek; Moller, Jacob E; Kober, Lars

    2013-01-01

    Renal dysfunction is associated with a variety of cardiac alterations including left ventricular (LV) hypertrophy, LV dilation, and reduction in systolic and diastolic function. It is common and associated with an increased mortality risk in heart failure (HF) patients. This study was designed to...

  12. Regional left ventricular diastolic function in hypertrophic cardiomyopathy

    To estimate regional left ventricular (LV) diastolic filling patterns in hypertrophic cardiomyopathy (HCM), a computer-assisted method by applying 'sector analysis' to ECG forward and reverse gated radionuclide ventriculography was developed. Fourteen patients with HCM (four with localized septal hypertrophy, seven with apical hypertrophy and three with septal and apical hypertrophy according to echocardiography) were observed at rest. After establishing serial 20 msec imaged frames, the LV region of interest was subdivided into eight sectors radiating from the geometric center. A time-activity curve was generated for each sector and was fitted by third-order harmonics of the Fourier series. From each fitted curve, the regional peak filling rate (rPFR) and the time to rPFR (rTPFR) in the forward gating method and regional atrial contribution to filling (rAC/FV) in the reverse gating method were calculated. The coefficient of variance of rTPFR was used as an index of LV diastolic asynchrony. In HCM, a prominent delay of rTPFR was observed in the hypertrophied regions. The coefficient of variance of rTPFR correlated inversely with global LVPFR (r=-0.62, p<0.05), indicating that diastolic asynchrony is one of the determinants of the LV early filling rate. Regional AC/FV was augmented in the hypertrophied regions, indicating the important role of atrial systolic LV filling for slowed early filling. Thus, this new method provides valuable information concerning regional diastolic LV wall mechanics in HCM. (author)

  13. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.

    Vandenberg, C A

    1987-01-01

    The mechanism of rectification of the inwardly rectifying potassium channel was examined with single-channel recording techniques in isolated ventricular myocytes from adult guinea pig heart. Inward, or anomalous, rectification describes the property that potassium (K) current can enter the cell at potentials negative to the potassium equilibrium potential, EK, more readily than it can leave the cell at positive potentials. Voltage ramps applied to single inward rectifier channels in cell-att...

  14. Mitochondrial networks in cardiac myocytes reveal dynamic coupling behavior.

    Kurz, Felix T; Derungs, Thomas; Aon, Miguel A; O'Rourke, Brian; Armoundas, Antonis A

    2015-04-21

    Oscillatory behavior of mitochondrial inner membrane potential (ΔΨm) is commonly observed in cells subjected to oxidative or metabolic stress. In cardiac myocytes, the activation of inner membrane pores by reactive oxygen species (ROS) is a major factor mediating intermitochondrial coupling, and ROS-induced ROS release has been shown to underlie propagated waves of ΔΨm depolarization as well as synchronized limit cycle oscillations of ΔΨm in the network. The functional impact of ΔΨm instability on cardiac electrophysiology, Ca(2+) handling, and even cell survival, is strongly affected by the extent of such intermitochondrial coupling. Here, we employ a recently developed wavelet-based analytical approach to examine how different substrates affect mitochondrial coupling in cardiac cells, and we also determine the oscillatory coupling properties of mitochondria in ventricular cells in intact perfused hearts. The results show that the frequency of ΔΨm oscillations varies inversely with the size of the oscillating mitochondrial cluster, and depends on the strength of local intermitochondrial coupling. Time-varying coupling constants could be quantitatively determined by applying a stochastic phase model based on extension of the well-known Kuramoto model for networks of coupled oscillators. Cluster size-frequency relationships varied with different substrates, as did mitochondrial coupling constants, which were significantly larger for glucose (7.78 × 10(-2) ± 0.98 × 10(-2) s(-1)) and pyruvate (7.49 × 10(-2) ± 1.65 × 10(-2) s(-1)) than lactate (4.83 × 10(-2) ± 1.25 × 10(-2) s(-1)) or β-hydroxybutyrate (4.11 × 10(-2) ± 0.62 × 10(-2) s(-1)). The findings indicate that mitochondrial spatiotemporal coupling and oscillatory behavior is influenced by substrate selection, perhaps through differing effects on ROS/redox balance. In particular, glucose-perfusion generates strong intermitochondrial coupling and temporal oscillatory stability. Pathological changes in specific catabolic pathways, which are known to occur during the progression of cardiovascular disease, could therefore contribute to altered sensitivity of the mitochondrial network to oxidative stress and emergent ΔΨm instability, ultimately scaling to produce organ level dysfunction. PMID:25902432

  15. Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes

    Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2+-channel current (ICa) through the opposite actions for two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of ICa by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on ICa was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function

  16. Ventricular Septal Defect

    ... in adults Atrial Septal Defect Ventricular Septal Defect Tetralogy of Fallot Atrioventricular Canal Defect Transposition of the Great Arteries ... Select Topic Atrial Septal Defect Ventricular Septal Defect Tetralogy of Fallot Atrioventricular Canal Defect Transposition of the Great Arteries ...

  17. Myocardial hypertrophy and the maturation of fatty acid oxidation in the newborn human heart.

    Yatscoff, Michael A; Jaswal, Jagdip S; Grant, Meghan R; Greenwood, Rachel; Lukat, Trish; Beker, Donna L; Rebeyka, Ivan M; Lopaschuk, Gary D

    2008-12-01

    After birth dramatic decreases in cardiac malonyl CoA levels result in the rapid maturation of fatty acid oxidation. We have previously demonstrated that the decrease in malonyl CoA is due to increased activity of malonyl CoA decarboxylase (MCD), and decreased activity of acetyl CoA carboxylase (ACC), enzymes which degrade and synthesize malonyl CoA, respectively. Decreased ACC activity corresponds to an increase in the activity of 5'-AMP activated protein kinase (AMPK), which phosphorylates and inhibits ACC. These alterations are delayed by myocardial hypertrophy. As rates of fatty acid oxidation can influence the ability of the heart to withstand an ischemic insult, we examined the expression of MCD, ACC, and AMPK in the newborn human heart. Ventricular biopsies were obtained from infants undergoing cardiac surgery. Immunoblot analysis showed a positive correlation between MCD expression and age. In contrast, a negative correlation in both ACC and AMPK expression and age was observed. All ventricular samples displayed some degree of hypertrophy, however, no differences in enzyme expression were found between moderate and severe hypertrophy. This indicates that increased expression of MCD, and the decreased expression of ACC and AMPK are important regulators of the maturation of fatty acid oxidation in the newborn human heart. PMID:18614968

  18. Mammary Hypertrophy in an Ovariohysterectomized Cat

    Pukay, B. P.; Stevenson, D.A.

    1983-01-01

    A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful.

  19. Cardiac myocyte-derived follistatin-like 1 prevents renal injury in a subtotal nephrectomy model.

    Hayakawa, Satoko; Ohashi, Koji; Shibata, Rei; Kataoka, Yoshiyuki; Miyabe, Megumi; Enomoto, Takashi; Joki, Yusuke; Shimizu, Yuuki; Kambara, Takahiro; Uemura, Yusuke; Yuasa, Daisuke; Ogawa, Hayato; Matsuo, Kazuhiro; Hiramatsu-Ito, Mizuho; van den Hoff, Maurice J B; Walsh, Kenneth; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-03-01

    Heart disease contributes to the progression of CKD. Heart tissue produces a number of secreted proteins, also known as cardiokines, which participate in intercellular and intertissue communication. We recently reported that follistatin-like 1 (Fstl1) functions as a cardiokine with cardioprotective properties. Here, we investigated the role of cardiac Fstl1 in renal injury after subtotal nephrectomy. Cardiac-specific Fstl1-deficient (cFstl1-KO) mice and wild-type mice were subjected to subtotal (5/6) nephrectomy. cFstl1-KO mice showed exacerbation of urinary albumin excretion, glomerular hypertrophy, and tubulointerstitial fibrosis after subtotal renal ablation compared with wild-type mice. cFstl1-KO mice also exhibited increased mRNA levels of proinflammatory cytokines, including TNF-? and IL-6, NADPH oxidase components, and fibrotic mediators, in the remnant kidney. Conversely, systemic administration of adenoviral vectors expressing Fstl1 (Ad-Fstl1) to wild-type mice with subtotal nephrectomy led to amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis, accompanied by reduced expression of proinflammatory mediators, NADPH oxidase components, and fibrotic markers in the remnant kidney. In cultured human mesangial cells, treatment with recombinant FSTL1 attenuated TNF-?-stimulated expression of proinflammatory cytokines. Treatment of mesangial cells with FSTL1 augmented the phosphorylation of AMP-activated protein kinase (AMPK), and inhibition of AMPK activation abrogated the anti-inflammatory effects of FSTL1. These data suggest that Fstl1 functions in cardiorenal communication and that the lack of Fstl1 production by myocytes promotes glomerular and tubulointerstitial damage in the kidney. PMID:25071081

  20. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    A. Medeiros

    2004-12-01

    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  1. Quantitative FDG-uptake by positron emission tomography in progressive hypertrophy of rat hearts in vivo

    Quantitative myocardial fluorodeoxyglucose positron emission tomography (FDG-PET) for assessing glucose uptake in vivo is reliable in normal rat heart. The objective of this study was to assess the applicability of myocardial FDG-PET on multiple occasions in the longitudinal disease process of progressive hypertrophy of rat heart. Six salt-sensitive Dahl rats (Dahl-S) developing progressive hypertrophy with subsequent dilated cardiomyopathy were compared with salt-resistant Dahl rats (controls). FDG-PET was applied twice at early stage (ES: 14-18 weeks) and at late stage (LS: 22-26 weeks) of hypertrophy. Standardized uptake value (SUV) was calculated for comparing between different animal weights and different injection dosages of FDG. For validating the quantitative study, radioactivity of a total of 36 tissue samples was compared with the corresponding PET values. The left ventricular mass in Dahl-S increased by 17% at ES and by 25% at LS. The SUV in Dahl-S was 95% of controls at ES and reduced to 62% at LS (P=0.023). The heart function started to deteriorate after LS. Linear regression analysis showed a good correlation between the radioactivity of tissue samples and PET values (Y=1.20 X, P2=0.979). Small animal PET studies on longitudinal multiple occasions in vivo were feasible and useful for the repeating assessment of glucose uptake. The reduction of glucose uptake in progressive hypertrophy of heart over time may precede its progression to heart failure. (author)

  2. Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis

    Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. Methods: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48 months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. Results: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca2+ transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Conclusion: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart

  3. Ventricular premature complexes

    Bockeria O.L.

    2015-03-01

    Full Text Available Ventricular premature beats are detected in about 5% of population. Treatment of ventricular premature beats is a challenge; the choice of tactics of treatment depends on the cause of its’ occurrence and its’ influence on the prognosis. Ventricular premature beats are divided into two major groups: benign and life-threatening. Inbenign ventricular premature beats antiarrhythmic therapy or RFA of arrhythmogenic zones are used in case of severe symptoms. Life-threatening ventricular premature beats are often associated with concomitant cardiac pathology. In this case, treatment of the underlying disease is a major challenge.

  4. Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates.

    Bowman, J C; Steinberg, S F; Jiang, T; Geenen, D.L.; Fishman, G I; Buttrick, P M

    1997-01-01

    Protein kinase C (PKC) activation in the heart has been linked to a hypertrophic phenotype and to processes that influence contractile function. To establish whether PKC activation is sufficient to induce an abnormal phenotype, PKCbeta was conditionally expressed in cardiomyocytes of transgenic mice. Transgene expression in adults caused mild and progressive ventricular hypertrophy associated with impaired diastolic relaxation, whereas expression in newborns caused sudden death associated wit...

  5. Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy.

    Indolfi, Ciro; Curcio, Antonio

    2014-05-01

    Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, was identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes. These advanced comprehensive analyses represent a major step forward in our understanding of cardiovascular physiopathology, providing a promising adjunctive target for possible therapeutic approaches, namely the miR-mediated paracrine signaling network. PMID:24743143

  6. L-type calcium channel targeting and local signalling in cardiac myocytes.

    Shaw, Robin M; Colecraft, Henry M

    2013-05-01

    In the heart, Ca(2+) influx via Ca(V)1.2 L-type calcium channels (LTCCs) is a multi-functional signal that triggers muscle contraction, controls action potential duration, and regulates gene expression. The use of LTCC Ca(2+) as a multi-dimensional signalling molecule in the heart is complicated by several aspects of cardiac physiology. Cytosolic Ca(2+) continuously cycles between ~100 nM and ~1 μM with each heartbeat due to Ca(2+) linked signalling from LTCCs to ryanodine receptors. This rapid cycling raises the question as to how cardiac myocytes distinguish the Ca(2+) fluxes originating through L-type channels that are dedicated to contraction from Ca(2+) fluxes originating from other L-type channels that are used for non-contraction-related signalling. In general, disparate Ca(2+) sources in cardiac myocytes such as current through differently localized LTCCs as well as from IP3 receptors can signal selectively to Ca(2+)-dependent effectors in local microdomains that can be impervious to the cytoplasmic Ca(2+) transients that drive contraction. A particular challenge for diversified signalling via cardiac LTCCs is that they are voltage-gated and, therefore, open and presumably flood their microdomains with Ca(2+) with each action potential. Thus spatial localization of Cav1.2 channels to different types of microdomains of the ventricular cardiomyocyte membrane as well as the existence of particular macromolecular complexes in each Cav1.2 microdomain are important to effect different types of Cav1.2 signalling. In this review we examine aspects of Cav1.2 structure, targeting and signalling in two specialized membrane microdomains--transverse tubules and caveolae. PMID:23417040

  7. Cricopharyngeal muscle hypertrophy: radiologic-anatomic correlation.

    Torres, W E; Clements, J L; Austin, G E; Knight, K

    1984-05-01

    There is a divergence of opinion concerning the cricopharyngeal muscle defect commonly seen in the pharyngoesophageal area on barium esophagram. Some observers believe this defect is the result of neuromuscular dysfunction with the demonstration of the unrelaxed muscle bundle; however, others believe it is the result of actual hypertrophy of the cricopharyngeal muscle. Radiologic and pathologic study of 24 unselected autopsy cases revealed cricopharyngeal hypertrophy in 13 cases by radiologic criteria. Histologic examination revealed that the cricopharyngeal muscle thickness was uniformly greater in these cases than in the radiographically normal cases. The cricopharyngeal muscle defect is associated with actual hypertrophy of the cricopharyngeal muscle in many cases. PMID:6609574

  8. Regression of altitude-produced cardiac hypertrophy.

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  9. Adenoid Hypertrophy in Adults: A case Series

    Rout, Manas Ranjan; Mohanty, Diganta; Y Vijaylaxmi; Bobba, Kamlesh; Metta, Chakradhar

    2012-01-01

    Adenoid hypertrophy is common in children. Size of the adenoid increases up to the age of 6 years, then slowly atrophies and completely disappears at the age of 16 years. Adenoid hypertrophy in adults is rare. Present study shows that adenoid hypertrophy is now increasing in adults because of various causes. Study has been conducted in the Department of ENT and Head & Neck Surgery, Alluri Sitarama Raju Academy of Medical science, Eluru, Andhra Pradesh, India. Study shows that incidence of ade...

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

    Mehmet Kanadaţý; Esmeray Acartürk

    2003-01-01

    Introduction: Asymmetric septal hypertrophy (ASH) is the most classical abnormality in hypertrophic cardiomy-opathy (HCM). Segmental hypertrophy of the left ventricle is less frequently observed. Some cases with papillary muscle hypertrophy (PMH) particularly associated with apical HCM and also ASH has been reported. Aim of the study: The aim of this study was to determine the frequency of PMH in patients with ASH. Material and methods: Two-dimensional echocardiographic examinations were perf...

  11. Future perspectives and potential implications of cardiac myocyte apoptosis.

    Haunstetter, A; Izumo, S

    2000-02-01

    Recent advances in the understanding of the molecular mechanisms of apoptosis has gained increasing interest in the cardiovascular research community. Apoptotic myocyte loss has been detected in different cardiac disease states such as ischemic heart disease and congestive heart failure. In addition, some evidence for the molecular mechanisms in cardiac myocyte apoptosis has been evolving, although at present the implications thereof for clinical cardiac disease are not known in most of the cases. Based on these new insights, it is the intention of this article to highlight some topics in apoptosis research that might be of particular interest to define the future role and potentials of new therapeutic approaches aimed at preventing myocyte apoptosis. PMID:10728403

  12. Genetic and clinical profile of Indian patients of idiopathic restrictive cardiomyopathy with and without hypertrophy

    Rai, Taranjit Singh; Ahmad, Shamim; Ahluwalia, Tarun Veer Singh; Ahuja, Monica; Bahl, Ajay; Saikia, Uma Nahar; Singh, Balvinder; Talwar, Kewal K; Khullar, Madhu

    Both idiopathic restrictive cardiomyopathy (IRCM) and hypertrophic cardiomyopathy (HCM) are part of the same disease spectrum and are due to sarcomeric gene mutations. A patient with restrictive physiology without left ventricular hypertrophy (LVH) would be diagnosed as IRCM, while one with LVH....... She had features consistent with restrictive physiology. Her father and sister had died of restrictive cardiomyopathy. IRCM and HCM with restrictive physiology, both are part of the clinical expression of MYH7 and TNNI3 mutations and lead to worse clinical onset and progression of the disease....

  13. Genital hypertrophy: A neonatal pseudotumor in females

    A newborn female presented with a perineal and pelvic pseudotumor due to genital hypertrophy. This entity should not be confused with interlabial or cul-de-sac masses that require surgical intervention. (orig.)

  14. Compensatory renal hypertrophy following uninephrectomy is calcineurin-independent

    Williams, Clintoria R.; Wynne, Brandi M; Walker, Makeeva; Hoover, Robert S; Gooch, Jennifer L.

    2014-01-01

    Calcineurin is a calcium-dependent phosphatase that is involved in many cellular processes including hypertrophy. Inhibition or genetic loss of calcineurin blocks pathological cardiac hypertrophy and diabetic renal hypertrophy. However, calcineurin does not appear to be involved in physiological cardiac hypertrophy induced by exercise. The role of calcineurin in a compensatory, non-pathological model of renal hypertrophy has not been tested. Therefore, in this study, we examined activation of...

  15. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6±1.6 vs. 4.1±0.5, p<0.01) and posterolateral wall (5.9±0.7 vs. 3.8±0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  16. Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

    F.S. Evangelista

    2003-12-01

    Full Text Available Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%. Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58% only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25% and myocyte dimension (13-20% increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

  17. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  18. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  19. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology

    Krishnamoorthi, Shankarjee; Perotti, Luigi E.; Borgstrom, Nils P.; Ajijola, Olujimi A.; Frid, Anna; Ponnaluri, Aditya V.; Weiss, James N.; Qu, Zhilin; Klug, William S.; Ennis, Daniel B.; Garfinkel, Alan

    2014-01-01

    We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations. PMID:25493967

  20. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

    Krishnamoorthi, Shankarjee; Perotti, Luigi E; Borgstrom, Nils P; Ajijola, Olujimi A; Frid, Anna; Ponnaluri, Aditya V; Weiss, James N; Qu, Zhilin; Klug, William S; Ennis, Daniel B; Garfinkel, Alan

    2014-01-01

    We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations. PMID:25493967

  1. Functions of Autophagy in Pathological Cardiac Hypertrophy

    LI, ZHENHUA; Wang, Jian; Yang, Xiao

    2015-01-01

    Pathological cardiac hypertrophy is the response of heart to various biomechanical and physiopathological stimuli, such as aging, myocardial ischemia and hypertension. However, a long-term exposure to the stress makes heart progress to heart failure. Autophagy is a dynamic self-degradative process necessary for the maintenance of cellular homeostasis. Accumulating evidence has revealed a tight link between cardiomyocyte autophagy and cardiac hypertrophy. Sophisticatedly regulated autophagy pr...

  2. Calcineurin signalling mechanisms in myocardial hypertrophy

    Jian-Chun Wang

    2010-12-01

    Full Text Available Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitutively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE (2000-2011, systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy.

  3. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  4. Voltage clamp analysis of ajmaline-induced block of potassium currents in ventricular myocytes

    Bahníková, M.; Matějovič, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    Brno : Brno University of Technology, 2002 - (Jan, J.; Kozumplík, J.; Provazník, I.), s. 217-219 ISBN 80-214-2633-0. ISSN 1211-412X. [Biosignal 2002. Brno (CZ), 26.06.2002-28.06.2002] Institutional research plan: CEZ:AV0Z2076919 Keywords : cardiac cell * potassium currents * ajmaline Subject RIV: BO - Biophysics

  5. The functional role of cardiac T-tubules in a model of rat ventricular myocytes

    Pásek, Michal; Šimurda, J.; Christé, G.

    2006-01-01

    Roč. 364, č. 1842 (2006), s. 1187-1206. ISSN 1364-503X Institutional research plan: CEZ:AV0Z20760514 Keywords : accumulation-depletion of ions * transverse tubule * heart Subject RIV: BO - Biophysics Impact factor: 2.282, year: 2006

  6. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle

    Dealmeida, A.; McQuinn, T. C.; Sedmera, David

    2007-01-01

    Roč. 100, - (2007), s. 1363-1370. ISSN 0009-7330 Institutional research plan: CEZ:AV0Z50450515 Keywords : chick embryo * hemodynamics * fetal surgery * hypoplastic left heart syndrome Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 9.721, year: 2007

  7. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and ...

  8. Physiological role of transverse-axial tubular system in cardiac ventricular myocytes: a simulation study

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

    Lyon : IEEE, 2005, s. 393-395. [Computers in cardiology. Lyon (FR), 25.09.2005-28.09.2005] Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * tubular system * quantitative modelling Subject RIV: BO - Biophysics

  9. Mechanotransduction pathways in skeletal muscle hypertrophy.

    Yamada, André Katayama; Verlengia, Rozangela; Bueno Junior, Carlos Roberto

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process. PMID:22171534

  10. Septal myocardial protection during cardiac surgery for prevention of right ventricular dysfunction

    Gerald Buckberg

    2008-11-01

    Full Text Available Postoperative right ventricular (RV failure is difficult to treat and develops from functional impairment of the underlying free wall and septum. This report describes the vital importance of the ventricular septum in RV structure /function relationships, demonstrates how the helical ventricular myocardial band model defines spatial geometry of the free wall and septum to provide architectural reasons for RV dynamic action, and focuses upon pathophysiologic reasons for adverse perioperative events resulting in right ventricular failure. Myocyte fiber orientation is the key to ventricular performance in health and disease. The transverse geometry of the free wall allows constriction (bellows type motion, whereas oblique septal fiber orientation and midline septal position is essential for ventricular twisting, the vital mechanism for RV ejection against increased pulmonary vascular resistance. The septum is considered “the lion or motor of RV performance”. This central muscle mass occupies ~40% of myocardial ventricular weight, and injury from impaired myocardial protection is a preventable event. Septal function should be the index of adequacy of myocardial protection and we will show echocardiographic evidence that the integrated cardioplegic method prevents its injury. Dysfunction of a normally functioning septum following surgical cardiac procedures calls for reevaluation of myocardial protection methods.

  11. Non invasive Measurements of Myocardial Hypertrophy in Patients with Essential Hypertension Treated with Eprosartan: Contribution of the Physics

    Cabrera Solé, Ricardo

    2007-04-01

    Objective: The main objective of this study was to evaluate the effects of the treatment with eprosartan on cardiac hypertrophy in hypertensive patients using the echocardiogram to measure the hypertrophy of left ventricle. We studied 60 untreated patients diagnosed of mild to moderate hypertension which received after the diagnosis 600 mg/day of eprosartan, a novel direct angiotensin inhibitor recently introduced to treat hypertension. All patients were submitted to a standard echocardiographic study before the treatment and after 6 months of it We evaluated by echocardiogram the following parameters: left ventricular septum and posterior wall thickness, left ventricular mass, E/A index of mitral flow considering abnormal when this index was less than 1, and left ventricular ejection fraction. Results: at the beginning we found a systolic/diastolic pressures of 165±9/ 96±4 mmHg compared with the end of study of 124±2/79±3 mmHg (phypertrophy and improve left ventricular diastolic function in patients with essential hypertension according with parameters measured with non invasive methods.

  12. Idiopathic Ventricular Tachycardia Arising From the Right Ventricular Apex

    Letsas, Konstantinos P; Efremidis, Michael; Tsikrikas, Spyros; Sideris, Antonios

    2013-01-01

    We present a rare case of idiopathic ventricular tachycardia arising from the right ventricular apex. The electrocardiographic and electrophysiological characteristics of this tachycardia are discussed.

  13. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present

  14. Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

    McCormick, K. M.; Schultz, E.

    1992-01-01

    This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another model of regeneration, but rather produces a unique environment which induces satellite cell migration and subsequent fiber formation in the interfascicular space. De novo fiber formation is apparently the principal mechanism for the hyperplasia reported to occur in the ALD muscle undergoing hypertrophy induced by wing-weighting.

  15. Segregation of Central Ventricular Conduction System Lineages in Early SMA+ Cardiomyocytes Occurs Prior to Heart Tube Formation

    Caroline Choquet; Laetitia Marcadet; Sabrina Beyer; Kelly, Robert G.; Lucile Miquerol

    2016-01-01

    The cardiac conduction system (CCS) transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB) and right and left branches (BBs). Conducting and contractile working myocytes share common cardiomyogenic progenitors, however the time at which the CCS lineage becomes specified is unclear. In order to study t...

  16. The effects of fibroblasts on wave dynamics in a mathematical model for human ventricular tissue

    Nayak, Alok Ranjan

    2016-01-01

    We present systematic numerical studies of electrical-wave propagation in two-dimensional (2D) and three-dimensional (3D) mathematical models, for human, ventricular tissue with myocyte cells that are attached (a) regularly and (b) randomly to distributed fibroblasts. In both these cases we show that there is a parameter regime in which single rotating spiral- and scroll-wave states (RS) retain their integrity and do not evolve to a state ST that displays spatiotemporal chaos and turbulence. However, in another range of parameters, we observe a transition from ST to RS states in both 2D or 3D domains and for both cases (a) and (b). Our studies show that the ST-RS transition and rotation period of a spiral or scroll wave in the RS state depends on (i) the coupling strength between myocytes and fibroblasts and (ii) the number of fibroblasts attached to myocytes. We conclude that myocyte-fibroblast coupling strength and the number of fibroblasts are more important for the ST-RS transition than the precise way in...

  17. Channel Activity of Cardiac Ryanodine Receptors (RyR2) Determines Potency and Efficacy of Flecainide and R-Propafenone against Arrhythmogenic Calcium Waves in Ventricular Cardiomyocytes.

    Savio-Galimberti, Eleonora; Knollmann, Bjrn C

    2015-01-01

    Flecainide blocks ryanodine receptor type 2 (RyR2) channels in the open state, suppresses arrhythmogenic Ca2+ waves and prevents catecholaminergic polymorphic ventricular tachycardia (CPVT) in mice and humans. We hypothesized that differences in RyR2 activity induced by CPVT mutations determines the potency of open-state RyR2 blockers like flecainide (FLEC) and R-propafenone (RPROP) against Ca2+ waves in cardiomyocytes. Using confocal microscopy, we studied Ca2+ sparks and waves in isolated saponin-permeabilized ventricular myocytes from two CPVT mouse models (Casq2-/-, RyR2-R4496C+/-), wild-type (c57bl/6, WT) mice, and WT rabbits (New Zealand white rabbits). Consistent with increased RyR2 activity, Ca2+ spark and wave frequencies were significantly higher in CPVT compared to WT mouse myocytes. We next obtained concentration-response curves of Ca2+ wave inhibition for FLEC, RPROP (another open-state RyR2 blocker), and tetracaine (TET) (a state-independent RyR2 blocker). Both FLEC and RPROP inhibited Ca2+ waves with significantly higher potency (lower IC50) and efficacy in CPVT compared to WT. In contrast, TET had similar potency in all groups studied. Increasing RyR2 activity of permeabilized WT myocytes by exposure to caffeine (150 M) increased the potency of FLEC and RPROP but not of TET. RPROP and FLEC were also significantly more potent in rabbit ventricular myocytes that intrinsically exhibit higher Ca2+ spark rates than WT mouse ventricular myocytes. In conclusion, RyR2 activity determines the potency of open-state blockers FLEC and RPROP for suppressing arrhythmogenic Ca2+ waves in cardiomyocytes, a mechanism likely relevant to antiarrhythmic drug efficacy in CPVT. PMID:26121139

  18. Bovine model of chronic ischemic cardiomyopathy: implications for ventricular assist device research.

    Bartoli, Carlo R; Sherwood, Leslie C; Giridharan, Guruprasad A; Slaughter, Mark S; Wead, William B; Prabhu, Sumanth D; Koenig, Steven C

    2013-12-01

    Ventricular assist devices (VADs) have emerged as a successful treatment option for advanced heart failure. The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves (n?=?17, 94??7?kg), 90??m microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end-organ blood flows were quantified with 15-?m fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test VAD and adjunctive biological therapies. PMID:23876076

  19. Postural control in women with breast hypertrophy

    Alessandra Ferreira Barbosa

    2012-07-01

    Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairment of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

  20. Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

    Arnol, M; Starc, V; Knap, B; Potocnik, N; Bren, A F; Kandus, A

    2008-02-01

    Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function. PMID:18190661