Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy.
Myocardial failure in dilated cardiomyopathy may result from subcellular alterations in contractile protein function, excitation-contraction coupling processes, or recovery metabolism. We used isometric force and heat measurements to quantitatively investigate these subcellular systems in intact left ventricular muscle strips from nonfailing human hearts (n = 14) and from hearts with end-stage failing dilated cardiomyopathy (n = 13). In the failing myocardium, peak isometric twitch tension, maximum rate of tension rise, and maximum rate of relaxation were reduced by 46% (p = 0.013), 51% (p = 0.003), and 46% (p = 0.018), respectively (37 degrees C, 60 beats per minute). Tension-dependent heat, reflecting the number of crossbridge interactions during the isometric twitch, was reduced by 61% in the failing myocardium (p = 0.006). In terms of the individual crossbridge cycle, the average crossbridge force-time integral was increased by 33% (p = 0.04) in the failing myocardium. In the nonfailing myocardium, the crossbridge force-time integral was positively correlated with the patient's age (r = 0.86, p less than 0.02), whereas there was no significant correlation with age in the failing group. The amount and rate of excitation-contraction coupling-related heat evolution (tension-independent heat) were reduced by 69% (p = 0.24) and 71% (p = 0.028), respectively, in the failing myocardium, reflecting a considerable decrease in the amount of calcium released and in the rate of calcium removal. The efficiency of the metabolic recovery process, as assessed by the ratio of initial heat to total activity-related heat, was similar in failing and nonfailing myocardium (0.54 +/- 0.03 versus 0.50 +/- 0.02, p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)
Hasenfuss
G
G
Department of Physiology and Biophysics, University of Vermont, Burlington.
Mulieri
L A
LA
Leavitt
B J
BJ
Allen
P D
PD
Haeberle
J R
JR
Alpert
N R
NR
D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology*; D003285:Contractile Proteins / Q000502:physiology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism
D003285:Contractile Proteins; D002118:Calcium