INFLUENCE OF ATP-SENSITIVE POTASSIUM CHANNEL MODULATORS ON ISCHEMIA-INDUCED FIBRILLATION IN ISOLATED RAT HEARTS
INFLUENCE OF ATP-SENSITIVE POTASSIUM CHANNEL MODULATORS ON ISCHEMIA-INDUCED FIBRILLATION IN ISOLATED RAT HEARTS
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DOI：
10.1016/0022-2828(89)90717-7
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发表时间：
1989-08-01
影响因子：
5
通讯作者：
SIEGL, PKS
中科院分区：
文献类型：
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作者：
WOLLEBEN, CD;SANGUINETTI, MC;SIEGL, PKS
我们已经证实了Kantor和他的同事的发现，即缺血诱导的大鼠心脏缺血引起的纤颤可以被ATP依赖的K通道阻断剂格列本脲预防。这些数据表明，阻断ATP依赖的钾电流[Ik(ATP)]是一种新的抗心律失常机制。通过评估另一种磺脲类IK阻滞剂甲苯丁胺(1 MM)和两种已知的激活心脏组织中这些通道的药物BRL 34915(10µm)和吡那地尔(30µm)的效果，进一步验证了这一假设。与格列本脲相似，甲苯磺丁胺也能有效地预防这个离体鼠心脏模型中的纤颤。IK(ATP)激动剂增加了心动过速的发生率，缩短了心脏发生纤颤所需的时间。联合应用甘草甜素和任何一种IK(ATP)激动剂均可阻止它们的作用。结论：在大鼠心脏灌流模型中，全心缺血时激活的三磷酸腺苷参与了心脏纤颤的发生。
We have confirmed the findings of Kantor and colleagues that ischemia-induced fibrillation in isolated Langendorff-perfused rat hearts can be prevented by glyburide, a blocker of ATP-dependent K channels. These data suggest that block of ATP-dependent K current [IK(ATP)] is a novel antiarrhythmic mechanism. This hypothesis was further tested by evaluating the effects of another sulfonylurea IK(ATP) blocker, tolbutamide (1 mM) and two agents known to activate these channels in cardiac tissue, BRL 34915 (10 .mu.M) and pinacidil (30 .mu.M). Similar to glyburide, tolbutamide was also effective in preventing fibrillation in this isolated rat heart model. The IK(ATP) activators enhanced the rate of tachycardia and shortened the time required for the hearts developed fibrillation. Coadministration of glycburide with either IK(ATP) activator prevented their effects. It is concluded that activation of IK(ATP) during global ischemia contributes to the development of fibrillation in the perfused rat heart model.