Kane K A, Parratt J R, Williams F M
Br J Pharmacol. 1984 Jun;82(2):349-57. doi: 10.1111/j.1476-5381.1984.tb10769.x.
Reperfusion-induced arrhythmias were elicited in the pentobarbitone-anaesthetized rat by occlusion of the left main coronary artery and subsequent release. These arrhythmias were rapid in onset, occurring within 20 s after release of the ligature, and were of short duration (1-2 min). Their severity was dependent upon the duration of the preceding occlusion. A 5 or 15 min occlusion period produced the most severe arrhythmias on release, the incidence of ventricular fibrillation being 56 and 50% respectively. Evidence that reperfusion had occurred was provided by fluorescein dye distribution and intramyocardial temperature studies. The severity of reperfusion arrhythmias and mortality was unaffected by bilateral vagotomy, beta-adrenoceptor blockade by atenolol (2 mg kg-1 i.v.) or a combination of the two. The incidence of reperfusion-induced ventricular fibrillation was significantly reduced by Org 6001 (which blocks the fast inward sodium current), melperone (which acutely prolongs the cardiac action potential duration) and bepridil (which blocks both fast and slow inward currents). It was unaffected by nitroglycerine and the calcium antagonists verapamil, prenylamine and nifedipine. We have shown that reperfusion-induced cardiac arrhythmias can be consistently elicited in the anaesthetized rat and that they are particularly susceptible to drugs that can block the fast inward sodium current.
通过结扎左冠状动脉主干并随后松开，在戊巴比妥麻醉的大鼠中诱发再灌注诱导的心律失常。这些心律失常发作迅速，在结扎松开后20秒内发生，且持续时间短（1 - 2分钟）。其严重程度取决于先前阻塞的持续时间。5分钟或15分钟的阻塞期在松开时产生最严重的心律失常，室颤发生率分别为56%和50%。通过荧光素染料分布和心肌内温度研究提供了再灌注发生的证据。双侧迷走神经切断术、阿替洛尔（2毫克/千克静脉注射）的β肾上腺素能受体阻断或两者联合，均不影响再灌注心律失常的严重程度和死亡率。Org 6001（阻断快速内向钠电流）、美哌隆（急性延长心脏动作电位持续时间）和苄普地尔（阻断快速和缓慢内向电流）可显著降低再灌注诱导的室颤发生率。硝酸甘油以及钙拮抗剂维拉帕米、普尼拉明和硝苯地平对其无影响。我们已经表明，在麻醉大鼠中可一致诱发再灌注诱导的心律失常，并且它们对能够阻断快速内向钠电流的药物特别敏感。
