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

D E Vatner·N Sato·K Kiuchi·R P Shannon·S F Vatner
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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 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.

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AnimalsCalcium ChannelsCalcium Channels, L-TypeCardiac Complexes, PrematureCardiac Output, LowCardiac Pacing, ArtificialDogsHeartHemodynamicsIsoproterenolMuscle ProteinsMyocardiumRyanodine Receptor Calcium Release ChannelVentricular Function, LeftJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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D E Vatner, N Sato, K Kiuchi, R P Shannon, S F Vatner. 1994. Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure.. https://doi.org/10.1161/01.cir.90.3.1423

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