Lynch J J, DiCarlo L A, Montgomery D G, Hassan T, Lucchesi B R
Am Heart J. 1986 Oct;112(4):752-8. doi: 10.1016/0002-8703(86)90470-9.
The electrophysiologic actions of pirmenol, an investigational class I antiarrhythmic agent, were evaluated in eight anesthetized dogs, 5 to 10 days after anterior myocardial infarction. Before administration of the drug, programmed ventricular stimulation failed to initiate nonsustained or sustained ventricular tachyarrhythmias (VT) in any of the postinfarction dogs. After the cumulative administration of 2.5, 5.0, and 10.0 mg/kg pirmenol, programmed stimulation initiated sustained VT in six of the eight postinfarction dogs tested, with one additional dog responding with reproducible nonsustained VT (15 to 20 monomorphic complexes) after pirmenol administration. Only one of eight postinfarction dogs tested remained noninducible throughout the pirmenol dosing schedule. Administration of pirmenol tended to increase ventricular excitation thresholds, relative (p less than 0.05 after 10 mg/kg) and effective refractory periods in ischemically injured ventricular myocardium, and increased the difference or disparity in relative (p less than 0.05 after 5.0 and 10.0 mg/kg) and effective (p less than 0.01 after 2.5, 5, and 10, mg/kg) refractory periods between ischemically injured and normal noninjured ventricular myocardium. These findings suggest a potential for the provocation or aggravation of ventricular arrhythmias by pirmenol in the setting of recent myocardial infarction.
在八只麻醉犬身上评估了实验性I类抗心律失常药物吡美诺的电生理作用，这些犬在急性心肌梗死后5至10天。在给药前，程控心室刺激未能在任何一只梗死后犬诱发非持续性或持续性室性心律失常（VT）。在累积给予2.5、5.0和10.0mg/kg吡美诺后，程控刺激在八只接受测试的梗死后犬中的六只诱发了持续性VT，另外一只犬在给予吡美诺后出现了可重复的非持续性VT（15至20个单形性复合体）。在整个吡美诺给药方案中，八只接受测试的梗死后犬中只有一只始终不能被诱发。吡美诺给药倾向于增加缺血性损伤心室心肌的相对（10mg/kg后p<0.05）和有效不应期的心室兴奋阈值，并增加缺血性损伤和正常未损伤心室心肌之间相对（5.0和10.0mg/kg后p<0.05）和有效（2.5、5和10mg/kg后p<0.01）不应期的差异或离散度。这些发现提示在近期心肌梗死情况下，吡美诺有诱发或加重室性心律失常的可能性。
