EXISTENCE OF THE FRANK-STARLING MECHANISM IN THE FAILING HUMAN HEART - INVESTIGATIONS ON THE ORGAN, TISSUE, AND SARCOMERE LEVELS

Background The Frank-Starling mechanism is one of the most important p hysiological 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 sarcom ere levels: (1) In excised human whole left ventricles (2 donor hearts , 5 failing hearts), diastolic and systolic pressure-volume relationsh ips were obtained. (2) In isolated muscle strip preparations from the left ventricular wall of donor hearts (n=14) and failing hearts from p atients with idiopathic dilated cardiomyopathy (n=21) and ischemic car diomyopathy (n=11), peak developed force was measured at different mus cle lengths of the preparation. (3) Skinned fiber preparations were ob tained from failing right and left ventricles (n=12). In all three stu dies, we clearly observed the existence of the Frank-Starling mechanis m: (1) In isolated failing human left ventricles, peak developed isome tric pressure is increased when the preload is elevated. (2) Peak deve loped tension is increased by approximate to 50% to 70% (P <.01) in le ft ventricular preparations of failing and nonfailing ventricles when the muscles are stretched from 90% to 100% optimum length. (3) An incr ease in sarcomere length leads to a sensitization of contractile prote ins of ventricular skinned fiber preparations from failing human heart s. At 1.9-mu m sarcomere length, the EC(50) value was 5.56+/-0.06, and at 2.3 mu m it was 5.70+/-0.05 (P<.01; n=7). Conclusions The Frank-St arling mechanism is maintained in end-stage failing human hearts, wher eas significant alterations of diastolic myocardial distensibility are evident in chronic heart failure.