Tosaki A, Viossat I, Braquet P
Institut Henri Beaufour, Les Ulis, France.
Can J Physiol Pharmacol. 1991 Apr;69(4):488-93. doi: 10.1139/y91-073.
Isolated hearts, excised from spontaneously hypertensive male rats treated orally with cicletanine, a new furopyridine anti-hypertensive drug, were subjected to 30 min of global ischemia followed by 10 min of reperfusion. The effect of cicletanine on reperfusion-induced arrhythmias in relation to 6-keto-PGF1 alpha and thromboxane (TXB2) release was studied. After 30 min of global ischemia, the incidence (total) of ventricular fibrillation (VF) and ventricular tachycardia (VT) was reduced by 2-week pretreatment of the rats with 30 and 100 mg/kg of cicletanine (VF, 33% at 30 mg/kg and 25% at 100 mg/kg vs. 91% in untreated rats; VT, 42% at 30 mg/kg and 42% at 100 mg/kg vs. 100% in untreated rats), while lower doses of cicletanine (3 and 10 mg/kg) failed to reduce the incidence of reperfusion-induced rhythm disturbances. Reperfusion of the ischemic myocardium resulted in a fivefold increase of 6-keto-PGF1 alpha and TXB2 release in the perfusion effluent of fibrillated hearts but not in the perfusion effluent of nonfibrillated hearts. Cicletanine failed to influence the reperfusion-stimulated release of 6-keto-PGF1 alpha and TXB2. These results indicate that the anti-arrhythmic effect of cicletanine in the reperfused myocardium is not related to PGI2 and thromboxane A2 release.
从经新型呋吡啶类抗高血压药物西氯他宁口服治疗的自发性高血压雄性大鼠体内取出离体心脏，使其经历30分钟全心缺血，随后再灌注10分钟。研究了西氯他宁对再灌注诱导的心律失常的影响及其与6-酮-前列环素F1α（6-keto-PGF1 alpha）和血栓素（TXB2）释放的关系。全心缺血30分钟后，用30毫克/千克和100毫克/千克西氯他宁对大鼠进行为期2周的预处理，可降低室颤（VF）和室性心动过速（VT）的发生率（总计）（VF：30毫克/千克时为33%，100毫克/千克时为25%，未治疗大鼠为91%；VT：30毫克/千克时为42%，100毫克/千克时为42%，未治疗大鼠为100%），而较低剂量的西氯他宁（3毫克/千克和10毫克/千克）未能降低再灌注诱导的节律紊乱的发生率。缺血心肌再灌注导致颤动心脏灌注流出液中6-酮-前列环素F1α和TXB2的释放增加五倍，但未颤动心脏的灌注流出液中则未增加。西氯他宁未能影响再灌注刺激的6-酮-前列环素F1α和TXB2的释放。这些结果表明，西氯他宁在再灌注心肌中的抗心律失常作用与前列环素I2（PGI2）和血栓素A2的释放无关。
