Mechanisms of preventive effect of nicorandil on ischaemia-induced ventricular tachyarrhythmia in isolated arterially perfused canine left ventricular wedges
Mechanisms of preventive effect of nicorandil on ischaemia-induced ventricular tachyarrhythmia in isolated arterially perfused canine left ventricular wedges
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DOI：
10.1111/j.1742-7843.2008.00242.x
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发表时间：
2008-06-01
影响因子：
3.1
通讯作者：
Yamada, Mitsuhiko
中科院分区：
文献类型：
--
作者：
Hirose, Masamichi;Tsujino, Natsuko;Yamada, Mitsuhiko
尼可地尔是否能有效预防急性心肌缺血期间的室性快速心律失常（VT）仍存在争议。我们研究了尼可地尔对急性心肌缺血期间诱发 VT 的影响。从动脉灌注的犬左心室楔的整个透壁壁记录光学动作电位。通过动脉闭塞20分钟产生缺血。在心内膜起搏期间，尼可地尔缩短了缺血前透壁壁的平均动作电位持续时间（APD），并在缺血期间进一步缩短了平均动作电位持续时间，且不增加APD的分散。 HMR1098 是肌膜 ATP 敏感 K(+) 通道的选择性阻断剂，在缺血前和缺血期间抑制尼可地尔引起的 APD 缩短。缺血会降低跨壁传导速度（CV）。在 HMR1098 不存在和存在的情况下，尼可地尔部分恢复 CV 的程度相似。相反，在没有尼可地尔的情况下，HMR1098 不会抑制缺血性传导减慢。尼可地尔抑制缺血期间局部CV分散的增加。 VT 起始的等时图显示，透壁表面的折返是由透壁表面的心外膜区域的激发引起的。尼可地尔显着增加透壁心外膜区域非兴奋区的大小，从而显着降低缺血期间诱发的室速的发生率。 HMR1098 抑制尼可地尔的这种作用。这些结果表明，尼可地尔主要通过激活肌膜 K(ATP) 通道增强心外膜失活来预防急性全身缺血期间的 VT。
Whether nicorandil is effective at preventing ventricular tachyarrhythmia (VT) during acute myocardial ischaemia is still controversial. We examined effects of nicorandil on the induction of VT during acute myocardial ischaemia. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges. Ischaemia was produced by arterial occlusion for 20 min. During endocardial pacing, nicorandil shortened mean action potential duration (APD) in the transmural wall before ischaemia and further shortened it during ischaemia without increasing dispersion of APD. HMR1098, a selective blocker of sarcolemmal ATP-sensitive K(+) channels, inhibited the shortening of APD by nicorandil before and during ischaemia. Ischaemia decreased transmural conduction velocity (CV). Nicorandil partially restored CV to a similar extent in the absence and presence of HMR1098. In contrast, HMR1098 did not suppress the ischaemic conduction slowing in the absence of nicorandil. Nicorandil suppressed the increased dispersion of local CV during ischaemia. Isochrone maps on the initiation of VT showed that reentry in the transmural surface resulted from the excitation of the epicardial region of transmural surface. Nicorandil significantly increased the size of non-excited area in the epicardial region of the transmural wall, thereby significantly reducing the incidence of VT induced during ischaemia. HMR1098 inhibited this effect of nicorandil. These results suggest that nicorandil prevents VT during acute global ischaemia primarily by augmenting the inactivation of epicardial muscle through the activation of sarcolemmal K(ATP) channels.