TY - JOUR
T1 - Existence of the Frank-Starling mechanism in the failing human heart
T2 - Investigations on the organ, tissue, and sarcomere levels
AU - Holubarsch, Christian
AU - Ruf, Thorsten
AU - Goldstein, Daniel J.
AU - Ashton, Robert C.
AU - Nicki, Werner
AU - Pieske, Burkert
AU - Pioch, Katja
AU - Lüdemann, Jens
AU - Wiesner, Sandra
AU - Hasenfuss, Gerd
AU - Posival, Herbert
AU - Just, Hanjörg
AU - Burkhoff, Daniel
PY - 1996
Y1 - 1996
N2 - Background: The Frank-Sterling 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.
AB - Background: The Frank-Sterling 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.
KW - contractility
KW - heart failure
KW - ventricles
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U2 - 10.1161/01.CIR.94.4.683
DO - 10.1161/01.CIR.94.4.683
M3 - Article
C2 - 8772688
AN - SCOPUS:9544240359
SN - 0009-7322
VL - 94
SP - 683
EP - 689
JO - Circulation
JF - Circulation
IS - 4
ER -