Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium.

Abstract

Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Human cardiomyocyte calcium handling and transverse tubules in mid‐stage of post‐myocardial‐infarction heart failure

“…This is an obvious departure from previously published studies of HF in human patients21 or animal studies, of which large animal models utilizing dogs or rabbits have been thought to provide the most clinically useful replacements 11. Nonetheless, although large animal models present with important similarities to humans, for example, with respect to excitation contraction coupling and contractile mechanisms, they also differ with respect to aetiology and have been reported to differ in aspects of cardiac function and response to injury;52, 53, 54 see also the review by Hasenfuss 11…”

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

“…The accelerated relaxation that occurs with an increase in stimulation frequency remains less well understood, but recent studies suggest that not only the faster intracellular calcium decline, but also the myofilament responsiveness plays a critical role. Given the fact that the altered frequency-dependent response is a critical modulator of cardiac function, and this modulating function is severely impaired in various cardiomyopathies [57,58], a better understanding of the mechanisms underlying frequency-dependent modulation of contractility and relaxation, including post-rest potentiation and extra-systolic beat behavior, may be paramount in development of treatment of these cardiomyopathies. Comparison of the force frequency relationships in various species.…”

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

“…SERCA-2a has been implicated as a marker for progressive hypertrophic growth and heart failure (8). It has been suggested that a decreased level of SERCA-2a is associated with impaired uptake of Ca 2+ into sarcoplasmic reticulum and contributes to slowing of relaxation in the failing human hearts (20).…”