Effect of potassium on the action of the KATP modulators cromakalim, pinacidil, or glibenclamide on arrhythmias in isolated perfused rat heart subjected to regional ischaemia.
Effect of potassium on the action of the KATP modulators cromakalim, pinacidil, or glibenclamide on arrhythmias in isolated perfused rat heart subjected to regional ischaemia.
复制标题
钾对 KATP 调节剂克罗卡林、吡那地尔或格列本脲对局部缺血离体灌注大鼠心律失常的作用的影响。
作者：
A. D'Alonzo;R. Darbenzio;T. Hess;J. Sewter;P. Sleph;G. Grover
目的
ATP敏感性钾通道开放剂cromakalim（n = 10）和pinacidil（n = 10），以及该通道的阻断剂格列本脲（n = 10），在不同浓度（2至8 mM）的外部钾（[K +] o）下进行离体灌注大鼠心脏局部缺血研究。
方法
分离心脏并在Langendorff装置上灌注。在缺血前10分钟给予溶剂（0.1%DMSO）、克罗卡林（10 μ M）、吡那地尔（10 μ M）或格列本脲（10 μ M）。然后闭塞左冠状动脉15 min，再灌注5 min。
结果
没有一种药物引起心率变化超过10%。在4和6 mM [K +] o时，cromakalim和pinacidil均增加（30%）冠状动脉血流，格列本脲降低（30%）冠状动脉血流。在溶剂组中，[K +] o的增加通过减少室颤而产生心律失常评分的浓度依赖性降低。未观察到[K +] o对缺血性室性心动过速的浓度依赖性影响。在缺血条件下，相对于增加[K +] o的作用，钾通道开放剂和格列本脲更显著地减少缺血性室性心动过速和心室颤动。
结论
缺血性室颤与[K +] o的变化呈负相关，而对室性心动过速的影响为全或无。无论是钾通道开放剂还是格列本脲，尽管[K +] o的变化，也没有引起显着的programmic活性。这些数据表明，钾通道开放剂和格列本脲均通过其在缺血期间消除两种不同的致瘤机制的能力显示出潜在的抗肿瘤活性。这也表明，室性心动过速和心室颤动的潜在机制耦合在大鼠缺血期间。
OBJECTIVE
The ATP sensitive potassium channel openers cromakalim (n = 10) and pinacidil (n = 10), and a blocker of this channel, glibenclamide (n = 10), were studied in isolated perfused rat hearts subjected to regional ischaemia at varying concentrations (2 to 8 mM) of external potassium ([K+]o).
METHODS
Hearts were isolated and perfused on a Langendorff apparatus. Vehicle (0.1% DMSO), cromakalim (10 microM), pinacidil (10 microM), or glibenclamide (10 microM) were given 10 min before ischaemia. The left coronary artery was then occluded for 15 min and reperfused for 5 min.
RESULTS
No agent caused more than a 10% change in heart rate. Both cromakalim and pinacidil increased (30%), and glibenclamide decreased (30%) coronary flow at 4 and 6 mM [K+]o. In the vehicle group, increases in [K+]o produced concentration dependent reductions in arrhythmia scores by decreasing ventricular fibrillation. No concentration dependent effects of [K+]o on ischaemic ventricular tachycardia was observed. Under ischaemic conditions, potassium channel openers and glibenclamide more markedly reduced ischaemic ventricular tachycardia and fibrillation relative to the effects of increased [K+]o.
CONCLUSIONS
Ischaemic ventricular fibrillation was inversely related to changes in [K+]o, whereas effects on ventricular tachycardia were all-or-none. Neither potassium channel openers nor glibenclamide elicited significant proarrhythmic activity despite variations in [K+]o. These data suggest that both potassium channel openers and glibenclamide display potential antiarrhythmic activity through their ability to abolish two distinct arrhythmogenic mechanisms during ischaemia. It is also suggested that the underlying mechanisms of ventricular tachycardia and fibrillation are coupled during ischaemia in the rat.