Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium.

Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  D. Bers,et al.  Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction? , 1988, Journal of molecular and cellular cardiology.

[2]  G. Hasenfuss,et al.  Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. An in vitro study under physiological experimental conditions. , 1993, Circulation.

[3]  N. Alpert,et al.  Contraction frequency dependence of twitch and diastolic tension in human dilated cardiomyopathy (tension-frequency relation in cardiomyopathy). , 1992, Basic research in cardiology.

[4]  N. Alpert,et al.  Regulation of myocardial Ca2+-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[5]  N. Alpert,et al.  The regulation of calcium cycling in stressed hearts. , 1992, Basic research in cardiology.

[6]  K. Boheler,et al.  Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. , 1990, The Journal of clinical investigation.

[7]  J KOCH-WESER,et al.  Analysis of the effects of changes in rate and rhythm upon myocardial contractility. , 1961, The Journal of pharmacology and experimental therapeutics.

[8]  J. Potter,et al.  The time-course of Ca2+ exchange with calmodulin, troponin, parvalbumin, and myosin in response to transient increases in Ca2+. , 1981, Biophysical journal.

[9]  N. Alpert,et al.  Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. , 1992, Circulation research.

[10]  N. Alpert,et al.  Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. , 1993, Circulation research.

[11]  G. Hasenfuss,et al.  Influence of the force-frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy. , 1994, European heart journal.

[12]  T. Levine,et al.  Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. , 1987, Cardiovascular research.

[13]  G. M. Briggs,et al.  Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. , 1990, The Journal of clinical investigation.

[14]  N. Alpert,et al.  Protection of Human Left Ventricular Myocardium From Cutting Injury With 2,3 -Butanedione Monoxime , 1989, Circulation research.

[15]  N. Alpert,et al.  Altered Myocardial Force‐Frequency Relation in Human Heart Failure , 1992, Circulation.

[16]  R. Solaro,et al.  Methods for Measuring Functional Properties of Sarcoplasmic Reticulum and Myofibrils in Small Samples of Myocardium , 1984 .

[17]  A. Mazzucco,et al.  Contractile Properties and Ca2+ Release Activit of the Sarcoplasmic Reticulum in Dilated Cardiomyopathy , 1992, Circulation.

[18]  J. Léger,et al.  Probing functional regions in cardiac isomyosins with monoclonal antibodies. , 1993, Biochemistry.

[19]  N. Paradise,et al.  Criteria for adequate oxygenation of isometric kitten papillary muscle. , 1981, The American journal of physiology.

[20]  R. Schwinger,et al.  Alterations of the force-frequency relationship in the failing human heart depend on the underlying cardiac disease. , 1992, Basic research in cardiology.

[21]  A. Lompré,et al.  Function of the sarcoplasmic reticulum and expression of its Ca2(+)-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. , 1990, Circulation research.

[22]  M. Feldman,et al.  Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy. , 1988, The Journal of clinical investigation.

[23]  K. Campbell,et al.  A monoclonal antibody to the Ca2+-ATPase of cardiac sarcoplasmic reticulum cross-reacts with slow type I but not with fast type II canine skeletal muscle fibers: an immunocytochemical and immunochemical study. , 1988, Cell motility and the cytoskeleton.

[24]  J. Potter,et al.  The calcium and magnesium binding sites on cardiac troponin and their role in the regulation of myofibrillar adenosine triphosphatase. , 1980, The Journal of biological chemistry.

[25]  Joseph W. Linhart,et al.  Effects of Changing Heart Rate in Man by Electrical Stimulation of the Right Atrium: Studies at Rest, during Exercise, and with Isoproterenol , 1965, Circulation.

[26]  E Erdmann,et al.  Intracellular Calcium Handling in Isolated Ventricular Myocytes From Patients With Terminal Heart Failure , 1992, Circulation.

[27]  M. Noble,et al.  The cardiac excitation-contraction cycle. , 1982, Pharmacology & therapeutics.

[28]  D. DeMets,et al.  Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. , 1991, The New England journal of medicine.

[29]  M. Crompton.  The role of Ca2+ in the function and dysfunction of heart mitochondria , 1990 .

[30]  F. Schoen,et al.  Reversal of the force-frequency relationship in working myocardium from patients with end-stage heart failure , 1988 .

[31]  H. Drexler,et al.  Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure. , 1994, Circulation research.

[32]  D. Bers,et al.  Relaxation of rabbit ventricular muscle by Na-Ca exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity. , 1989, Circulation research.

[33]  S. Izumo,et al.  Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca(2+)-ATPase gene. , 1992, Circulation research.

[34]  T. Takahashi,et al.  Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy. , 1992, Circulation research.

[35]  W Grossman,et al.  Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. , 1987, Circulation research.

[36]  M. Bristow,et al.  Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy. , 1989, Circulation research.

[37]  J Ross,et al.  Enhancement of the Force‐Frequency Effect on Myocardial Contractility by Adrenergic Stimulation in Conscious Dogs , 1992, Circulation.

[38]  R. O'rourke,et al.  Influence of Heart Rate on Left Ventricular Performance in Conscious Dogs , 1987, Circulation research.

[39]  E. Carafoli.  The homeostasis of calcium in heart cells. , 1985, Journal of molecular and cellular cardiology.