title: Existence of the Frank-Starling mechanism in the failing human heart. Investigations on the organ, tissue, and sarcomere levels.
abstract: 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.
  
  
  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 approximately 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-microns sarcomere length, the EC50 value was 5.56 +/- 0.06, and at 2.3 microns 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.
authors.affiliation: University of Freiburg, Department of Cardiology and Angiology, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Holubarsch
authors.forename: T
authors.initials: T
authors.lastname: Ruf
authors.forename: D J
authors.initials: DJ
authors.lastname: Goldstein
authors.forename: R C
authors.initials: RC
authors.lastname: Ashton
authors.forename: W
authors.initials: W
authors.lastname: Nickl
authors.forename: B
authors.initials: B
authors.lastname: Pieske
authors.forename: K
authors.initials: K
authors.lastname: Pioch
authors.forename: J
authors.initials: J
authors.lastname: Lüdemann
authors.forename: S
authors.initials: S
authors.lastname: Wiesner
authors.forename: G
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: H
authors.initials: H
authors.lastname: Posival
authors.forename: H
authors.initials: H
authors.lastname: Just
authors.forename: D
authors.initials: D
authors.lastname: Burkhoff
mesh_terms: D000704:Analysis of Variance; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology* / Q000601:surgery; D003971:Diastole; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D016027:Heart Transplantation; D006352:Heart Ventricles; D006801:Humans; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009200:Myocardial Contraction; D012016:Reference Values; D012518:Sarcomeres / Q000502:physiology*; D013318:Stroke Volume; D013599:Systole