Rapid ventricular pacing for 1 day in dogs reduced 3H-ryanodine receptor binding from 1013 to 808 fmol/mg and depressed physiological responses, suggesting early changes in excitation-contraction coupling.
Changes in excitation-contraction coupling and decreased ryanodine receptor density occur early in the development of pacing-induced heart failure in dogs, suggesting a role in the pathogenesis of contractile abnormalities.
p-value: p=< .05
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 microgram/kg per minute was depressed by a significantly greater amount (P < .05), 52 +/- 7%, at 1 day after pacing. 3H-ryanodine receptor binding fell from 1013 +/- 25 to 808 +/- 42 fmol/mg after 1 day of pacing and remained depressed at similar levels (782 +/- 61 fmol/mg) at 4 to 7 weeks when heart failure was manifest. Ryanodine receptor affinity was unchanged from control values. Neither dihydropyridine binding nor affinity for 3H-PN200-110 was changed from control levels. Within 5 days after recovery from 1 day of pacing, physiological responses to isoproterenol, postextrasystolic potentiation, and mechanical restitution recovered, as did 3H-ryanodine binding density. CONCLUSIONS: These findings suggest that the changes in excitation-contraction coupling and potentially the sarcoplasmic reticulum calcium release channel occur early in the development of heart failure and therefore may be important in the pathogenesis of the contractile abnormalities in this disease state.
Vatner et al. (1994) studied Heart failure. Rapid ventricular pacing vs. Control values (baseline) was evaluated on Myocardial contractile function, mechanical restitution response, and 3H-ryanodine receptor binding (p=< .05). Rapid ventricular pacing for 1 day in dogs reduced 3H-ryanodine receptor binding from 1013 to 808 fmol/mg and depressed physiological responses, suggesting early changes in excitation-contraction coupling.