Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation.
Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation.
复制标题
钙和钙通道在心室颤动的引发和维持中的作用。
DOI：
10.1161/01.res.67.5.1115
复制
发表时间：
1990
影响因子：
20.1
通讯作者：
Guarnieri,T
中科院分区：
文献类型：
--
作者：
Merillat,JC;Lakatta,EG;Hano,O;Guarnieri,T
心室颤动（VF）发生和维持过程中的细胞事件知之甚少。我们开发了一种非缺血性，隔离，灌注兔Langendorff制备中，持续VF可以诱导交流电流（AC），并允许灌注液成分的变化。我们还使用Na（+）-K+泵抑制（10 μ M哇巴因或无K（+）灌注液）诱导VF。AC刺激或Na（+）-K+泵抑制总是引发VF。钙通道阻滞维拉帕米或尼群地平均匀抑制VF的启动在两个模型中。在Na（+）-K+泵抑制过程中，1）尽管有Ca 2+超载的证据，但钙通道阻滞可预防VF; 2）ryanodine或河豚毒素Na+通道阻滞消除自发肌浆网产生的胞浆Ca 2+振荡并不能预防VF的发生。将细胞外[Ca 2 +]降低至80 μ M可均匀地阻止由于Na（+）-K+泵抑制而不是由于AC刺激引起的VF的起始。还使用1）灌注液[Ca 2 +]减少，2）Ca 2+通道阻断或3）电除颤研究了VF维持。将灌注液[Ca 2 +]降低至80 μ M导致VF期间的除颤，无论是由AC还是Na（+）-K+泵抑制诱导的。维拉帕米或尼群地平也导致除颤，无论启动方法。电除颤仅在AC诱导的VF中成功。结果表明，VF可以启动和维持在非缺血性兔Langendorff准备。这些数据表明，慢通道Ca 2+通量的增加，而不是增加胞质Ca 2+本身，是必要的启动和维持VF。然而，这些数据并不排除胞质Ca 2+在VF调制中的重要作用。
The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.