静脉注射胺碘酮治疗室性心律失常延迟起效的机制探讨

Mechanism of the Delayed Onset of Action after IntravenousAmiodarone for Treatment of Ventricular Arrhythmias

静注胺碘酮(Am)治疗室性心律失常时起效时间常出现数小时以上的延迟.为探讨其延迟作用的机制,在8条活体杂种狗身上采用快速静注Am后连续滴注Am20h的方法,对Am及其主要活性代谢产物去乙基胺碘酮(DA)的血浆、心肌内浓度与相应时间段的电生理参数变化进行系列比较.结果发现,静注Am后血浆和心肌内Am和DA浓度都迅速达峰,此时窦性心动周期和文氏点都显著延长(分别与用药前比P<0.05),而心室有效不应期(VERP)和心室激动时间(VAT)只有轻度的、统计学上无显著性的增加.连续静滴Am期间,血浆和心肌内Am和DA浓度均很快下降,到30min和60min时稳定在一个较低水平,20h后窦性心动周期和文氏周期恢复至接近用药前水平,但VERP和VAT并不随着Am和DA浓度降低而缩短.表明静注Am抗心律失常延迟起效不能用心肌内Am或DA浓度蓄积来解释,静注Am抗心律失常的确切机制尚待研究.

The onset of action after intravenous amiodarone (Am) for treatment of ventricular arrhythmias often ocurrs after at least several hours' delay. To investigate the mechanism of this delayed action, we gave intravenous Am initial loading dose of 2.5 mg/kg or 5.0 mg/kg over 10 min, followed immediately by infusion of 7.5 μg/(kg·min) or 10 μg/(kg·min) for 20 h in 8 dogs. The concentration of Am and its major metabolite, Ndesethylamiodarone (DA) in plasma and myocardial tissue were determined just after loading the dose and 20 h after infusion respectively, while electrophysiologic parameters were measured at each corresponding time. The concentration of Am and DA in plasma were also determined serially. The results showed that the concentration of Am or DA in plasma or myocardial tissue rose to the peak level within 5～15 min after loading the dose; the sinus cycle length and AV conduction Wenchbach point measured at this time increased significantly compared with those at baseline (P<0.05), while ventricular effective refractory period (VERP) and ventricular activation time (VAT) at this time increased in significantly (P>0.05). The concentration of Am or DA in plasma or myocardial tissue declined rapidly during the continuous infusion period and kept stable low level after 30～60 min infusion. The sinus cycle length and AV conduction Wenchbach point shortened to near the baseline level, while VERP and VAT did not show any shortening 20 h after infusion. The delayed onset of action for treatment of ventricular arrhythmias after intravenous administration of Am cannot be explained by higher concentration of Am or DA in myocardial tissue. The exact mechanisms of intravenous Am for treating arrhythmias remain to be studied.