Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure

Abstract

Background: Rapid ventricular pacing for 1 day reduced myocardial contractile function without inducing heart failure in conscious, chronically instrumented dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed further and overt signs of congestive heart failure, eg, ascites, dyspnea, and edema, were evident. Methods and Results: The mechanical restitution response, a physiological index of calcium release, was depressed at 1 day of rapid ventricular pacing. Postextrasystolic potentiation was also depressed by a similar amount, 14±3%, at 1 day after pacing. The response to isoproterenol 0.2 μg/kg per minute was depressed by a significantly greater amount (P