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°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