Contractile protein function in failing and nonfailing human myocardium.
Isometric heat and force measurements were used to relate mechanical performance to function of contractile proteins in muscle strips from failing and nonfailing human hearts (37 degrees C, 60 beats per minute). Compared to control myocardium, crossbridge behavior was altered in myocardium from hearts with end-stage failing dilated and ischemic cardiomyopathy, resulting in increased crossbridge force-time integral by 33% and 36%, respectively. Peak isometric twitch tension was reduced significantly by 46% in muscle strips from hearts with dilated cardiomyopathy. In myocardium from hearts with ischemic cardiomyopathy peak isometric twitch tension was comparable to values from nonfailing hearts. Including all three types of myocardium, there was a close correlation between the number of crossbridge interactions during the isometric twitch (tension-dependent heat) and peak twitch tension (r = 0.88; p less than 0.001). Compared to control, in failing myocardium from dilated cardiomyopathic hearts, tension-independent heat (calcium cycling) was significantly reduced. This indicates that in dilated cardiomyopathy reduced peak twitch tension results from decreased calcium activation of contractile proteins with reduced number of crossbridge interactions during the isometric twitch. In ischemic cardiomyopathy mechanisms different from those observed in dilated cardiomyopathy seem to be involved in the development of heart failure.
Hasenfuss
G
G
Department of Medicine, Cardiology, University of Freiburg, FRG.
Mulieri
L A
LA
Leavitt
B J
BJ
Allen
P D
PD
Holubarsch
C
C
Just
H
H
Alpert
N R
NR
D000205:Actomyosin / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003285:Contractile Proteins / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry; D013599:Systole / Q000502:physiology
D003285:Contractile Proteins; D000205:Actomyosin; D002118:Calcium