Gloor H O, Urthaler F, James T N
J Clin Invest. 1983 May;71(5):1457-66. doi: 10.1172/jci110899.
Amiodarone was selectively perfused into the sinus node artery and atrioventricular node artery of 51 dogs. Amiodarone had an immediate negative chronotropic and dromotropic effect. Threshold concentration was 2.5 micrograms/ml. 25 and 50 micrograms/ml of amiodarone injected into the sinus node artery slowed the heart by 25.6 +/- 3.1 and 33.7 +/- 2.6 beats/min (mean +/- 1 SEM), respectively. Amiodarone 25 and 50 micrograms/ml injected into the AV node artery during AV junctional rhythm slowed the AV junctional pacemaker by 12.2 +/- 1.8 and 17.4 +/- 1.7 beats/min, respectively. Injections of amiodarone into the AV node artery during sinus rhythm regularly increased AV conduction time sometimes causing 2 degrees AV block at the highest concentration used. Impaired conduction was exclusively measured at the level of the A-H interval in the His electrogram. Neither atropine nor propranolol prevented the negative chronotropic effects of amiodarone. Amiodarone had no significant effect on sinus node response to either stellate stimulation or intranodal administration of norepinephrine. The negative chronotropic action of amiodarone was significantly enhanced when amiodarone was administered in a perfusate containing low (0.6 mM) instead of normal calcium. Taken collectively these observations indicate that amiodarone has immediate depressant electrophysiologic effects on both the sinus node and the AV junction and that these early effects might involve the blockade of the slow channel.
将胺碘酮选择性灌注到51只犬的窦房结动脉和房室结动脉。胺碘酮具有即刻负性变时和变传导作用。阈浓度为2.5微克/毫升。向窦房结动脉注射25微克/毫升和50微克/毫升的胺碘酮,心率分别减慢25.6±3.1次/分和33.7±2.6次/分(均值±1标准误)。在房室交界性心律时,向房室结动脉注射25微克/毫升和50微克/毫升的胺碘酮,房室交界性起搏点频率分别减慢12.2±1.8次/分和17.4±1.7次/分。在窦性心律时向房室结动脉注射胺碘酮,常使房室传导时间延长,在所用最高浓度时有时可导致二度房室传导阻滞。传导障碍仅在希氏电图的A-H间期水平测量。阿托品和普萘洛尔均不能阻止胺碘酮的负性变时作用。胺碘酮对窦房结对星状神经节刺激或结内注射去甲肾上腺素的反应无显著影响。当胺碘酮在含低钙(0.6毫摩尔)而非正常钙的灌注液中给药时,其负性变时作用显著增强。综合这些观察结果表明,胺碘酮对窦房结和房室交界均有即刻的电生理抑制作用,且这些早期作用可能涉及对慢通道的阻滞。