Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure.
Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure.
复制标题
在心力衰竭发展早期，心肌兰尼碱受体减少并改变兴奋-收缩耦合。
DOI：
10.1161/01.cir.90.3.1423
复制
发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Vatner,SF
中科院分区：
文献类型：
--
作者：
Vatner,DE;Sato,N;Kiuchi,K;Shannon,RP;Vatner,SF
研究背景在清醒、长期使用仪器的狗中，快速心室起搏1天可降低心肌收缩功能，而不诱发心力衰竭。起搏4至7周后，心肌收缩力进一步受到抑制，充血性心力衰竭的明显体征（例如腹水、呼吸困难和水肿）明显。方法和结果机械恢复反应（钙释放的生理指标）在快速心室起搏1天时受到抑制。在起搏后1天，期外收缩后增强也被抑制了相似的量，14 +/-3%。在起搏后1天，对异丙肾上腺素0.2微克/公斤/分钟的反应被显著抑制（P <0.05），为52 +/-7%。起搏1天后，3 H-ryanodine受体结合从1013 +/- 25降至808 +/- 42 fmol/mg，4 - 7周时心力衰竭明显时，3 H-ryanodine受体结合仍保持在相似水平（782 +/- 61 fmol/mg）。Ryanodine受体亲和力与对照值相比无变化。与对照水平相比，二氢吡啶结合和对3 H-PN 200 -110的亲和力均未发生变化。起搏1天后恢复5天内，对异丙肾上腺素的生理反应、期外收缩后增强和机械恢复，3 H-ryanodine结合密度也是如此。收缩偶联和潜在的肌浆网钙释放通道在心力衰竭的发展早期发生，因此在收缩性心力衰竭的发病机制中可能是重要的。这种疾病状态的异常。
BACKGROUNDRapid 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 RESULTSThe 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.CONCLUSIONSThese 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.