Force-frequency relations and response to ryanodine in failing rabbit hearts.

Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia.