Effect of ryanodine on ventricular fibrillation induced by myocardial ischaemia.
Effect of ryanodine on ventricular fibrillation induced by myocardial ischaemia.
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兰尼定对心肌缺血引起的心室颤动的影响。
DOI：
10.1093/cvr/27.12.2152
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发表时间：
1993
影响因子：
10.8
通讯作者：
Billman,GE
中科院分区：
文献类型：
--
作者：
Lappi,MD;Billman,GE
目的：心肌缺血可引起胞浆钙升高，进而引发恶性室性心律失常。最近，抑制钙进入已被证明可以预防这些致命的心律失常。然而，细胞质储存的钙释放对心律紊乱的影响尚未得到研究。本研究探讨了肌浆网钙释放在致死性室性心律失常引发中的作用。方法：长期用仪器测量杂种狗的左心室压力、冠状动脉血流量和心电活动（心室心电图）。手术期间结扎左冠状动脉前降支，造成心肌梗塞。此外，在左回旋动脉周围放置液压封堵器。然后通过急性心肌缺血和运动相结合的方式评估心室颤动的易感性。结果：在运动加缺血试验中，10只动物诱发了心室颤动。第二天，在用兰尼定（10 μg·kg−1，n = 10）（一种削弱肌浆网钙流出的药物）预处理后，重复运动加缺血试验。 Ryanodine 未能预防缺血引起的心室颤动。 Ryanodine 显着 (p<0.01) 增加心率 [对照 115.3(SEM 6.3)vryanodine 156.4(14.7) 次·min−1]，但降低左心室收缩压 [对照 141.8(4.9)vryanodine 111.1(12.7) mm Hg] 和正左心室 dP/dt休息和运动时均为[3312.9(217.4)vryanodine 1462.9(226.3) mm Hg·s−1]。相比之下，该药物消除了哇巴因毒性引起的室性心动过速（n = 10，40 μg·kg−1 推注，然后 0.076 μg·kg−1·min−1 持续 1 小时，然后 20 μg·kg−1 推注，静脉注射）。结论：这些数据表明，肌浆网中兰尼碱敏感通道的钙释放可能对室性心动过速有显着贡献。哇巴因毒性引起的心律失常，但不引起缺血引起的心室颤动。心血管研究1993；27：2152-2159
Objective:Myocardial ischaemia can provoke a rise in cytosolic calcium which may in turn trigger malignant ventricular arrhythmias. Recently, inhibition of calcium entry has been shown to prevent these lethal arrhythmias. However, the contributions of calcium release from cytosolic stores to these disruptions in cardiac rhythm have not been investigated. This study examines the role of calcium release from the sarcoplasmic reticulum in the initiation of lethal ventricular arrhythmias.Methods:Mongrel dogs were chronically instrumented to measure left ventricular pressure, coronary blood flow, and cardiac electrical activity (ventricular electrocardiogram). The left anterior descending coronary artery was ligated during the surgery to produce a myocardial infarction. In addition, a hydraulic occluder was placed around the left circumflex artery. The susceptibility to ventricular fibrillation was then evaluated by the combination of acute myocardial ischaemia and exercise.Results:Ventricular fibrillation was induced in 10 animals during the exercise plus ischaemia test. On a subsequent day the exercise plus ischaemia test was repeated after pretreatment with ryanodine (10 μg·kg−1, n = 10), a drug which impairs calcium efflux from the sarcoplasmic reticulum. Ryanodine failed to prevent ventricular fibrillation induced by ischaemia. Ryanodine significantly (p<0.01) increased heart rate [control 115.3(SEM 6.3)vryanodine 156.4(14.7) beats·min−1] but reduced left ventricular systolic pressure [control 141.8(4.9)vryanodine 111.1(12.7) mm Hg] and positive left ventricular dP/dt [3312.9(217.4)vryanodine 1462.9(226.3) mm Hg·s−1] both at rest and during exercise. In contrast, this drug abolished ventricular tachycardia induced by ouabain toxicity (n = 10, 40 μg·kg−1bolus followed by 0.076 μg·kg−1·min−1for 1 h, then 20 μg·kg−1bolus, intravenously).Conclusions:These data suggest that calcium release from ryanodine sensitive channels in the sarcoplasmic reticulum may contribute significantly to the arrhythmias induced by ouabain toxicity but not to ventricular fibrillation provoked by ischaemia.Cardiovascular Research1993;27:2152-2159