Existence of the Frank-Starling mechanism in the failing human heart: Investigations on the organ, tissue, and sarcomere levels

Christian Holubarsch, Thorsten Ruf, Daniel J. Goldstein, Robert C. Ashton, Werner Nicki, Burkert Pieske, Katja Pioch, Jens Lüdemann, Sandra Wiesner, Gerd Hasenfuss, Herbert Posival, Hanjörg Just, Daniel Burkhoff

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)683-689
Number of pages7
JournalCirculation
Volume94
Issue number4
StatePublished - 1996
Externally publishedYes

Fingerprint

Starlings
Sarcomeres
Heart Ventricles
Muscles
Tissue Donors
Blood Pressure
Contractile Proteins
Dilated Cardiomyopathy
Cardiomyopathies
Myocardium
Heart Failure
Pressure

Keywords

  • contractility
  • heart failure
  • ventricles

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Holubarsch, C., Ruf, T., Goldstein, D. J., Ashton, R. C., Nicki, W., Pieske, B., ... Burkhoff, D. (1996). Existence of the Frank-Starling mechanism in the failing human heart: Investigations on the organ, tissue, and sarcomere levels. Circulation, 94(4), 683-689.

Existence of the Frank-Starling mechanism in the failing human heart : Investigations on the organ, tissue, and sarcomere levels. / Holubarsch, Christian; Ruf, Thorsten; Goldstein, Daniel J.; Ashton, Robert C.; Nicki, Werner; Pieske, Burkert; Pioch, Katja; Lüdemann, Jens; Wiesner, Sandra; Hasenfuss, Gerd; Posival, Herbert; Just, Hanjörg; Burkhoff, Daniel.

In: Circulation, Vol. 94, No. 4, 1996, p. 683-689.

Research output: Contribution to journalArticle

Holubarsch, C, Ruf, T, Goldstein, DJ, Ashton, RC, Nicki, W, Pieske, B, Pioch, K, Lüdemann, J, Wiesner, S, Hasenfuss, G, Posival, H, Just, H & Burkhoff, D 1996, 'Existence of the Frank-Starling mechanism in the failing human heart: Investigations on the organ, tissue, and sarcomere levels', Circulation, vol. 94, no. 4, pp. 683-689.
Holubarsch, Christian ; Ruf, Thorsten ; Goldstein, Daniel J. ; Ashton, Robert C. ; Nicki, Werner ; Pieske, Burkert ; Pioch, Katja ; Lüdemann, Jens ; Wiesner, Sandra ; Hasenfuss, Gerd ; Posival, Herbert ; Just, Hanjörg ; Burkhoff, Daniel. / Existence of the Frank-Starling mechanism in the failing human heart : Investigations on the organ, tissue, and sarcomere levels. In: Circulation. 1996 ; Vol. 94, No. 4. pp. 683-689.
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abstract = "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.",
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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

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