Shigematsu S, Sato T, Arita M
Department of Physiology, Oita Medical University, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):283-90. doi: 10.1007/pl00005169.
The effects of various class I antiarrhythmic drugs and glibenclamide were examined on the recovery of contraction during reperfusion, in relation to the action potential duration (APD) seen during ischemia. Action potential and contractile tension were recorded from isolated guinea pig right ventricular muscles perfused with oxygenated Tyrode solution via the coronary artery. Ten minutes of no-flow ischemia shortened the APD at 90% of repolarization level (APD90) to 58% of control (pre-ischemic values). The APD90 was completely restored after 60 min of reperfusion. The developed tension was abolished during ischemia and recovered to 87% of control after 60 min of reperfusion. In the presence of Vaughan Williams class Ia drug cibenzoline (5 microM) or an ATP-sensitive potassium (K(ATP)) channel blocker glibenclamide (10 microM), the shortening of the APD90 during ischemia was significantly attenuated. However, the recovery of developed tension was significantly inhibited. Class Ic drug pilsicainide (10 microM) did not affect the ischemia-induced shortening of the APD90 or the recovery of developed tension after reperfusion. In the presence of class Ib drug mexiletine (10 microM), the shortening of the APD90 during ischemia was significantly facilitated. The recovery of developed tension in the presence of mexiletine tended to be improved, although the difference was not statistically significant. The developed tension measured after the 60 min reperfusion period following 20 min of no-flow ischemia was markedly depressed, indicating the presence of myocardial stunning. Mexiletine and pilsicainide significantly improved the recovery of developed tension and diminished the stunning. We conclude that cibenzoline and glibenclamide, which block cardiac K(ATP) channels inhibit contractile recovery after reperfusion by attenuating the shortening of APD during ischemia. In contrast, mexiletine, which activates K(ATP) channels (in addition to blockade of Na+ channels) improves contractile recovery by facilitating the shortening of APD during ischemia.
研究了多种Ⅰ类抗心律失常药物和格列本脲对再灌注期间收缩恢复的影响，并与缺血期间观察到的动作电位时程（APD）相关。通过冠状动脉用含氧的台氏液灌注豚鼠右心室分离肌肉，记录动作电位和收缩张力。十分钟的无血流缺血将复极化水平90%时的动作电位时程（APD90）缩短至对照（缺血前值）的58%。再灌注60分钟后，APD90完全恢复。缺血期间收缩张力消失，再灌注60分钟后恢复至对照的87%。在存在沃恩·威廉姆斯Ⅰa类药物西苯唑啉（5微摩尔）或ATP敏感性钾（K(ATP)）通道阻滞剂格列本脲（10微摩尔）的情况下，缺血期间APD90的缩短显著减弱。然而，收缩张力的恢复受到显著抑制。Ⅰc类药物吡西卡尼（10微摩尔）不影响缺血诱导的APD90缩短或再灌注后收缩张力的恢复。在存在Ⅰb类药物美西律（10微摩尔）的情况下，缺血期间APD90的缩短显著加速。尽管差异无统计学意义，但在美西律存在下收缩张力的恢复有改善趋势。无血流缺血20分钟后再灌注60分钟测得的收缩张力明显降低，表明存在心肌顿抑。美西律和吡西卡尼显著改善了收缩张力的恢复并减轻了顿抑。我们得出结论，阻断心脏K(ATP)通道的西苯唑啉和格列本脲通过减弱缺血期间APD的缩短来抑制再灌注后的收缩恢复。相反，激活K(ATP)通道（除了阻断钠通道）的美西律通过促进缺血期间APD的缩短来改善收缩恢复。
