Circulation, Vol 85, 1743-1750, Copyright © 1992 by American Heart Association
LA Mulieri, G Hasenfuss, B Leavitt, PD Allen and NR Alpert
BACKGROUND. In congestive heart failure (idiopathic dilated
cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease
in end-diastolic left ventricular volume, depressed peak rates of left
ventricular pressure rise and fall, and depressed heart-rate- dependent
potentiation of contractility (bowditch treppe). We studied contractile
function of isolated left ventricular myocardium from New York Heart
Association class IV-failing and nonfailing hearts at physiological
temperature and heart rates in order to identify and quantitate
abnormalities in myocardial function that underlie abnormal ventricular
function. METHODS AND RESULTS. The isometric tension- generating ability of
isolated left ventricular strips from nonfailing and failing human hearts
was investigated at 37 degrees C and contraction frequencies ranging from
12 to 240 per minute (min-1). Strips were dissected using a new method of
protection against cutting injury with 2,3-butanedione monoxime (BDM) as a
cardioplegic agent. In nonfailing myocardium the twitch tension-frequency
relation is bell- shaped developing 25 +/- 2 mN/mm2 at a contraction
frequency of 72 min- 1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction
frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve
occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22
min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001)
less tension than in nonfailing myocardium at 72 and 174 min-1,
respectively. Between 60 and 150 min-1 tension increases by 107% in
nonfailing myocardium, but it does not change significantly in failing
myocardium. Peak rates of rise and fall of isometric twitch tension vary in
parallel with twitch tension as stimulation frequency rises in nonfailing
myocardium but not in failing myocardium. CONCLUSIONS. The quantitative
agreement between these results from isolated myocardium and those from
catheterization laboratory measurements on intact humans suggest that
alterations of myocardial origin, independent of systemic factors, may
contribute to the above mentioned abnormalities in left ventricular
function seen in dilated cardiomyopathy.
ARTICLES
Altered myocardial force-frequency relation in human heart failure
Department of Physiology and Biophysics, University of Vermont College of Medicine, Medical Center Hospital of Vermont, Burlington 05405.
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G. Hasenfuss, W. Schillinger, S. E. Lehnart, M. Preuss, B. Pieske, L. S. Maier, J. Prestle, K. Minami, and H. Just Relationship Between Na+-Ca2+–Exchanger Protein Levels and Diastolic Function of Failing Human Myocardium Circulation, February 9, 1999; 99(5): 641 - 648. [Abstract] [Full Text] [PDF]
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S. E. Harding, C. H. Davies, A. M. Money-Kyrle, and P. A. Poole-Wilson An inhibitor of nitric oxide synthase does not increase contraction or {beta}-adrenoceptor sensitivity of ventricular myocytes from failing human heart Cardiovasc Res, December 1, 1998; 40(3): 523 - 529. [Abstract] [Full Text] [PDF]
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B. Stein, T. Eschenhagen, J. Rudiger, H. Scholz, U. Forstermann, and I. Gath Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1179 - 1186. [Abstract] [Full Text] [PDF]
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H. Sugawara and M. Endoh A Novel Cardiotonic Agent SCH00013 Acts as a Ca++ Sensitizer with No Chronotropic Activity in Mammalian Cardiac Muscle J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 214 - 222. [Abstract] [Full Text]
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M Morikawa, H Sato, H Sato, Y Koretsune, Y Ohnishi, T Kurotobi, T Kuzuya, and M Hori Sustained left ventricular diastolic dysfunction after exercise in patients with dilated cardiomyopathy Heart, September 1, 1998; 80(3): 263 - 269. [Abstract] [Full Text]
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C Mittmann, T Eschenhagen, and H Scholz Cellular and molecular aspects of contractile dysfunction in heart failure Cardiovasc Res, August 1, 1998; 39(2): 267 - 275. [Full Text] [PDF]
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K. Dipla, J. A. Mattiello, V. Jeevanandam, S. R. Houser, and K. B. Margulies Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure Circulation, June 16, 1998; 97(23): 2316 - 2322. [Abstract] [Full Text] [PDF]
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L. S. Maier, R. Brandes, B. Pieske, and D. M. Bers Effects of left ventricular hypertrophy on force and Ca2+ handling in isolated rat myocardium Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1361 - H1370. [Abstract] [Full Text] [PDF]
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G. Hasenfuss Alterations of calcium-regulatory proteins in heart failure Cardiovasc Res, February 1, 1998; 37(2): 279 - 289. [Full Text] [PDF]
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S. Richard, F. Leclercq, S. Lemaire, C. Piot, and J. Nargeot Ca2+ currents in compensated hypertrophy and heart failure Cardiovasc Res, February 1, 1998; 37(2): 300 - 311. [Abstract] [Full Text] [PDF]
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M. A Movsesian and R. H.G Schwinger Calcium sequestration by the sarcoplasmic reticulum in heart failure Cardiovasc Res, February 1, 1998; 37(2): 352 - 359. [Full Text] [PDF]
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M. C. Schaub, M. A. Hefti, R. A. Zuellig, and I. Morano Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms Cardiovasc Res, February 1, 1998; 37(2): 381 - 404. [Abstract] [Full Text] [PDF]
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T. Neumann, U. Ravens, and G. Heusch Characterization of excitation-contraction coupling in conscious dogs with pacing-induced heart failure Cardiovasc Res, February 1, 1998; 37(2): 456 - 466. [Abstract] [Full Text] [PDF]
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K. R Sipido, T. Stankovicova, W. Flameng, J. Vanhaecke, and F. Verdonck Frequency dependence of Ca2+ release from the sarcoplasmic reticulum in human ventricular myocytes from end-stage heart failure Cardiovasc Res, February 1, 1998; 37(2): 478 - 488. [Abstract] [Full Text] [PDF]
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K. Mubagwa, P. Kaplan, B. Shivalkar, M. Miserez, V. Leunens, M. Borgers, and W. Flameng Calcium uptake by the sarcoplasmic reticulum, high energy content and histological changes in ischemic cardiomyopathy Cardiovasc Res, February 1, 1998; 37(2): 515 - 523. [Abstract] [Full Text] [PDF]
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A. R.W. Money-Kyrle, C. H. Davies, H. K. Ranu, P. O'Gara, N. Singh Kent, P. A. Poole-Wilson, and S. E. Harding The role of cAMP in the frequency-dependent changes in contraction of guinea-pig cardiomyocytes Cardiovasc Res, February 1, 1998; 37(2): 532 - 540. [Abstract] [Full Text] [PDF]
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J. Weil, T. Eschenhagen, S. Hirt, O. Magnussen, C. Mittmann, U. Remmers, and H. Scholz Preserved Frank-Starling mechanism in human end stage heart failure Cardiovasc Res, February 1, 1998; 37(2): 541 - 548. [Abstract] [Full Text] [PDF]
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C. Holubarsch, J Ludemann, S Wiessner, T. Ruf, H Schulte-Baukloh, S Schmidt-Schweda, B Pieske, H Posival, and H Just Shortening versus isometric contractions in isolated human failing and non-failing left ventricular myocardium: dependency of external work and force on muscle length, heart rate and inotropic stimulation Cardiovasc Res, January 1, 1998; 37(1): 46 - 57. [Abstract] [Full Text] [PDF]
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B. D. Hoit, N. Ball, and R. A. Walsh Invasive hemodynamics and force-frequency relationships in open- versus closed-chest mice Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2528 - H2533. [Abstract] [Full Text] [PDF]
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P. Lechat, S. Escolano, J. L. Golmard, H. Lardoux, S. Witchitz, J. A. Henneman, B. Maisch, M. Hetzel, P. Jaillon, J.-P. Boissel, et al. Prognostic Value of Bisoprolol-Induced Hemodynamic Effects in Heart Failure During the Cardiac Insufficiency BIsoprolol Study (CIBIS) Circulation, October 7, 1997; 96(7): 2197 - 2205. [Abstract] [Full Text]
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E. J. Eichhorn and M. R. Bristow Medical Therapy Can Improve the Biological Properties of the Chronically Failing Heart: A New Era in the Treatment of Heart Failure Circulation, November 1, 1996; 94(9): 2285 - 2296. [Abstract] [Full Text]
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S. F. Khoury, B. D. Hoit, V. Dave, C. M. Pawloski-Dahm, Y. Shao, M. Gabel, M. Periasamy, and R. A. Walsh Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca2+-Cycling Proteins in the Baboon: Implications for the Force-Frequency and Relaxation-Frequency Relationships Circ. Res., October 1, 1996; 79(4): 727 - 735. [Abstract] [Full Text]
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M. Flesch, R. H.G. Schwinger, F. Schiffer, K. Frank, M. Sudkamp, F. Kuhn-Regnier, G. Arnold, and M. Bohm Evidence for Functional Relevance of an Enhanced Expression of the Na+-Ca2+ Exchanger in Failing Human Myocardium Circulation, September 1, 1996; 94(5): 992 - 1002. [Abstract] [Full Text]
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B. Andersson, K. Caidahl, A. di Lenarda, S. E. Warren, F. Goss, A. Waldenstrom, S. Persson, I. Wallentin, A. Hjalmarson, and F. Waagstein Changes in Early and Late Diastolic Filling Patterns Induced by Long-term Adrenergic ß-Blockade in Patients With Idiopathic Dilated Cardiomyopathy Circulation, August 15, 1996; 94(4): 673 - 682. [Abstract] [Full Text]
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C. Holubarsch, T. Ruf, D. J. Goldstein, R. C. Ashton, W. Nickl, B. Pieske, K. Pioch, J. Ludemann, S. Wiesner, G. Hasenfuss, et al. Existence of the Frank-Starling Mechanism in the Failing Human Heart: Investigations on the Organ, Tissue, and Sarcomere Levels Circulation, August 15, 1996; 94(4): 683 - 689. [Abstract] [Full Text]
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H. R. Figulla, F. Gietzen, U. Zeymer, M. Raiber, J. Hegselmann, R. Soballa, and R. Hilgers Diltiazem Improves Cardiac Function and Exercise Capacity in Patients With Idiopathic Dilated Cardiomyopathy: Results of the Diltiazem in Dilated Cardiomyopathy Trial Circulation, August 1, 1996; 94(3): 346 - 352. [Abstract] [Full Text]
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C. Piot, S. Lemaire, B. Albat, J. Seguin, J. Nargeot, and S. Richard High Frequency–Induced Upregulation of Human Cardiac Calcium Currents Circulation, January 1, 1996; 93(1): 120 - 128. [Abstract] [Full Text]
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R. H.G. Schwinger, M. Bohm, U. Schmidt, P. Karczewski, U. Bavendiek, M. Flesch, E.-G. Krause, and E. Erdmann Unchanged Protein Levels of SERCA II and Phospholamban but Reduced Ca2+ Uptake and Ca2+-ATPase Activity of Cardiac Sarcoplasmic Reticulum From Dilated Cardiomyopathy Patients Compared With Patients With Nonfailing Hearts Circulation, December 1, 1995; 92(11): 3220 - 3228. [Abstract] [Full Text]
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C. Holubarsch, R. Schneider, B. Pieske, T. Ruf, G. Hasenfuss, G. Fraedrich, H. Posival, and H. Just Positive and Negative Inotropic Effects of DL-Sotalol and D-Sotalol in Failing and Nonfailing Human Myocardium Under Physiological Experimental Conditions Circulation, November 15, 1995; 92(10): 2904 - 2910. [Abstract] [Full Text]
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C.H. Davies, K. Davia, J.G. Bennett, J.R. Pepper, P.A. Poole-Wilson, and S.E. Harding Reduced Contraction and Altered Frequency Response of Isolated Ventricular Myocytes From Patients With Heart Failure Circulation, November 1, 1995; 92(9): 2540 - 2549. [Abstract] [Full Text]
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