Spontaneous heart failure in SHHF rats was associated with a 53% depression of maximal Ca2+-activated force, with slowed Ca2+ cycling partially compensating for myofilament dysfunction.
BACKGROUND: Chronic congestive heart failure is a common, often lethal disorder of cardiac contractility. The fundamental pathophysiology of the contractile failure remains unclear, the focus being on abnormal Ca2+ cycling despite emerging evidence for depressed myofilament function. METHODS AND RESULTS: We measured intracellular Ca2+ concentration (Ca2+i) and contractile force in intact ventricular muscle from SHHF rats with spontaneous heart failure and from age-matched controls. At physiological concentrations of extracellular Ca2+ (Ca2+o), Ca2+i transients were equal in amplitude in the 2 groups, but Ca2+i peaked later in SHHF muscles. Twitch force peaked slowly and was equivalent or modestly decreased in amplitude relative to controls. Steady-state analysis revealed a much greater (53%) depression of maximal Ca2+-activated force in SHHF muscles, which, had other factors been equal, would have produced an equivalent suppression of twitch force. Phase-plane analysis reveals that the slowing of Ca2+ cycling prolongs the time available for Ca2+ to activate the myofilaments in failing muscle, partially compensating for the marked dysfunction of the contractile machinery. CONCLUSIONS: Our results indicate that myofilament activation is severely blunted in heart failure, but concomitant changes in Ca2+i kinetics minimize the contractile depression. These results challenge prevailing concepts regarding the pathophysiology of heart failure: the myofilaments emerge as central players, whereas changes in Ca2+ cycling are reinterpreted as compensatory rather than causative.
Pérez et al. (Tue,) conducted a other in Chronic congestive heart failure. Spontaneous heart failure vs. Age-matched controls was evaluated on Intracellular Ca2+ concentration and contractile force. Spontaneous heart failure in SHHF rats was associated with a 53% depression of maximal Ca2+-activated force, with slowed Ca2+ cycling partially compensating for myofilament dysfunction.