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目的:考察化合物CPUY11018对心电复极的影响,评估其潜在致心律失常作用。方法:观察CPUY11018和阿奇利特对正常豚鼠心率(HR)、QT间期、校正QT间期(QTc)及校正QT间期离散度(QTcd,QTcmax～QTcm in)的影响;正常家兔连续给予异丙肾上腺素(5 mg.kg-1.d-1,sc)7 d,诱发心肌缺血性肥厚,甲氧胺法观察CPUY11018对肥厚心肌尖端扭转性室性心动过速(TdP)的诱发作用。结果:小剂量CPUY11018可浓度依赖性延长QT间期,药物剂量为0.203 mg.kg-1时,其对豚鼠心电图的影响达到平台,加大给药剂量,心电图并无明显改变,显示出明显的“自限”特征;甲氧胺法诱发家兔TdP模型中CPUY11018(0.15和0.3 mg.kg-1.m in-1)无诱发TdP心律失常作用。结论:CPUY11018对QT间期有限延长,诱发心肌病变家兔TdP上作用弱。此作用可能与化合物兼具钙通道阻断作用有关。
OBJECTIVE: To investigate the effect of compound CPUY11018 on electrocardiogram repolarization and assess its potential role in arrhythmia. Methods: The effects of CPUY11018 and aztreon on heart rate (HR), QT interval, QTc and QTcmax QTcm in normal guinea pigs were observed. Normal rabbits Myocardial ischemic hypertrophy was induced by isoproterenol (5 mg.kg-1.d-1, sc) for 7 days, and the effect of CPUY11018 on TdP in hypertrophic myocardium was observed by methoxyamine method Induced effect. Results: Small dose of CPUY11018 could prolong the QT interval in a concentration-dependent manner. When the drug dose was 0.203 mg.kg-1, the effect on the electrocardiogram of guinea pigs reached a platform. With increasing dosage, the electrocardiogram did not change obviously, “Self-limiting ” features; methoxylamine induced rabbit TdP model CPUY11018 (0.15 and 0.3 mg.kg-1.m in-1) did not induce arrhythmia of TdP. CONCLUSION: CPUY11018 has a limited prolongation of QT interval and weak effects on TdP in rabbits with cardiomyopathy. This effect may be related to the compound and calcium channel blockade.