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(Circulation. 1996;94:683-689.)
© 1996 American Heart Association, Inc.
Articles |
Existence of the Frank-Starling Mechanism in the Failing Human Heart
Investigations on the Organ, Tissue, and Sarcomere Levels
the University of Freiburg, Internal Medicine, Department of Cardiology and Angiology, Freiburg, Germany (C.H., T.R., W.N., B.P., K.P., J.L., S.W., G.H., H.J.); the Department of Cardiovascular Surgery and Heart Transplantation, Bad Oeynhausen, Germany (H.P.); and the College of Physicians and Surgeons, Columbia University, New York, NY (D.J.G., R.C.A., D.B.). Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 1994.
Correspondence to Prof Dr Ch Holubarsch, University of Freiburg, Internal Medicine, Department of Cardiology and Angiology, Hugstetter Str 55, 79106 Freiburg, FRG.
Background The Frank-Starling mechanism is one of the most important physiological principles for regulation of contractile performance. We therefore studied the question of whether this mechanism may be absent or attenuated in end-stage failing human left ventricular myocardium.
Methods and Results Different methodological approaches were used to analyze the effects of this mechanism on the organ, tissue, and sarcomere levels: (1) In excised human whole left ventricles (2 donor hearts, 5 failing hearts), diastolic and systolic pressure-volume relationships were obtained. (2) In isolated muscle strip preparations from the left ventricular wall of donor hearts (n=14) and failing hearts from patients with idiopathic dilated cardiomyopathy (n=21) and ischemic cardiomyopathy (n=11), peak developed force was measured at different muscle lengths of the preparation. (3) Skinned fiber preparations were obtained from failing right and left ventricles (n=12). In all three studies, we clearly observed the existence of the Frank-Starling mechanism: (1) In isolated failing human left ventricles, peak developed isometric pressure is increased when the preload is elevated. (2) Peak developed tension is increased by 
50% to 70% (P<.01) in left ventricular preparations of failing and nonfailing ventricles when the muscles are stretched from 90% to 100% optimum length. (3) An increase in sarcomere length leads to a sensitization of contractile proteins of ventricular skinned fiber preparations from failing human hearts. At 1.9-µm sarcomere length, the EC50 value was 5.56±0.06, and at 2.3 µm it was 5.70±0.05 (P<.01; n=7).
Conclusions The Frank-Starling mechanism is maintained in end-stage failing human hearts, whereas significant alterations of diastolic myocardial distensibility are evident in chronic heart failure.
Key Words: heart failure • contractility • ventricles
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