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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization.
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Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization.

机译：与局部缺血相反的变化是，与去极化相关的离子跨膜交换的改变导致了I类和IV类抗心律不齐药物的抗纤颤作用。

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摘要

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.
机译：已知I类抗心律不齐药物在严重缺血时会丧失抗纤颤活性，而IV类抗心律不齐药物具有这种活性。心动过速也是一种去极化因子，最近已显示出引起离子跨膜交换的改变，这在钙的情况下尤为明显。这使人们想知道，缺血导致的抗心律不齐药物的抗纤颤活性变化是否取决于同一过程。在正常条件下研究重度缺血的抗纤颤活性的变化，其中包括I类抗心律不齐药物氟卡尼（1.00 mg x kg（-1）加0.04 mg x kg（-1）x min（-1），a钠通道阻滞剂和IV类抗心律失常药物维拉帕米（50 microg x kg（-1）加2 microg x kg（-1）x min（-1））（钙通道阻滞剂）进行实验。在确定持续时间增加的缺血期（30、60、120、180、300和420 s）的缺血期结束时，通过确定心室纤颤阈值（VFT）评估每个通道的最终阻滞作用。通过导入心内膜下电极（心率每分钟180次），通过持续100 ms的舒张期刺激来确定，通过完全闭塞左冠状动脉前降支来诱发局部缺血，记录单相动作电位同时测量心室常规传导时间（VCT）。单相动作电位持续时间（MAPD）随纤维的膜极化而变化。氟卡尼对钠通道的阻断，通常会提高VFT（7.0 +/- 0.4至13.8 +/- 0.8 mA，p <0.001）并延长VCT（28 +/- 3至44 +/- 5 ms，p <0.001 ），在缺血过程中失去作用。这导致缺血诱导的VFT下降的反作用降低，并且缺血诱导的VCT延长的加重降低。钙通道的阻塞通常不会改变VFT（7.2 +/- 0.6到8.4 +/- 0.7 mA，ns）或VCT（30 +/- 2到34 +/- 3 ms，ns），通常不会改变缺血引起的VFT下降。 VFT需要更多的时间才能达到0 mA，从而延迟了原纤化的开始。膜去极化本身受到反对，因为MAPD的缩短和VCT的延长也被延迟了。因此，在缺血期间钠通道在心室纤维的节律性收缩期去极化中所起的作用逐渐减少。这降低或抑制了钠通道阻滞剂对兴奋性或传导的作用，并增加了钙通道阻滞剂在减轻局部缺血引起的疾病中的作用。

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