Coker S J
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
J Pharmacol Methods. 1989 Jul;21(4):263-79. doi: 10.1016/0160-5402(89)90064-8.
Experiments were performed to assess the feasibility of using anesthetized rabbits for the study of ischemia- and reperfusion-induced arrhythmias. Initial studies indicated that occlusion of the left anterior descending coronary artery produced ectopic activity in only one out of eight rabbits. All rabbits subject to occlusion of the left circumflex artery below where it emerges from under the left atrial appendage had ECG changes (ST-segment elevation, Lead II), 80% had arrhythmias, and 50% died in ventricular fibrillation during the first 20 min of coronary artery occlusion. Subsequent reperfusion in the survivors produced further arrhythmias in the majority of rabbits, and one fibrillated. Although a high incidence of ectopic activity was also observed in rabbits subject to occlusion of the left circumflex artery close to its origin, or both the left anterior descending and circumflex arteries, this was accompanied by marked reductions in arterial blood pressure. Thus, occlusion of the left circumflex artery at the lower site was chosen for all further studies. Quinidine hydrochloride 10 mg kg-1 (n = 10) or bretylium tosylate 20 mg kg-1 (n = 10) administered 15 min prior to coronary artery occlusion reduced the incidence of ischemia-induced ventricular fibrillation to 10% compared with 60% in controls (n = 15). Although bretylium reduced arterial blood pressure and heart rate, neither drug altered the hemodynamic consequences of coronary artery occlusion (e.g., increased left ventricular end diastolic pressure). Bretylium at doses of 5 and 20 mg kg-1, but not quinidine, reduced the ST-segment elevation that developed during the ischemic period. The ability to detect the antifibrillatory activity of quinidine and bretylium suggests that the anesthetized rabbit may provide a useful alternative or additional model for the study of arrhythmias induced by acute myocardial ischemia.
进行实验以评估使用麻醉兔研究缺血和再灌注诱导的心律失常的可行性。初步研究表明，结扎左冠状动脉前降支仅在八只兔中的一只产生异位活动。所有接受结扎左回旋支在其从左心耳下方发出处以下部位的兔均有心电图改变（ST段抬高，II导联），80% 出现心律失常，50% 在冠状动脉结扎的最初20分钟内心室颤动死亡。存活兔随后的再灌注在大多数兔中产生了进一步的心律失常，一只发生了颤动。尽管在结扎左回旋支靠近其起始处或同时结扎左冠状动脉前降支和回旋支的兔中也观察到高发生率的异位活动，但这伴随着动脉血压的显著降低。因此，在所有进一步的研究中选择在较低部位结扎左回旋支。在冠状动脉结扎前15分钟给予盐酸奎尼丁10 mg·kg⁻¹（n = 10）或溴苄铵20 mg·kg⁻¹（n = 10），与对照组（n = 15）的60% 相比，缺血诱导的心室颤动发生率降低至10%。尽管溴苄铵降低了动脉血压和心率，但两种药物均未改变冠状动脉结扎的血流动力学后果（例如，左心室舒张末期压力升高）。5和20 mg·kg⁻¹剂量的溴苄铵可降低缺血期出现的ST段抬高，但奎尼丁无此作用。检测奎尼丁和溴苄铵抗颤动活性的能力表明，麻醉兔可能为研究急性心肌缺血诱导的心律失常提供一种有用的替代或补充模型。
