Gough W B, Zeiler R H, Barreca P, El-Sherif N
J Cardiovasc Pharmacol. 1982 May-Jun;4(3):375-80. doi: 10.1097/00005344-198205000-00006.
Commercial intravenous amiodarone has been reported to have antiarrhythmic actions and to cause only mild hypotension in humans. In the dog, however, amiodarone was observed to cause severe hypotension. Since commercial intravenous amiodarone is amiodarone compound (50 mg/ml) dissolved in water with polysorbate 80 (Tween 80) (100 mg/kg), the effects of amiodarone in ethanol (5 mg/kg) and polysorbate 80 (10 mg/kg) were studied individually, and in combination in anesthetized dogs. Commercial intravenous amiodarone and polysorbate 80 caused at least a 60% drop in mean blood pressure and left ventricular maximum dP/dt for at least 30 min, whereas amiodarone in ethanol did not. The drop in blood pressure was not principally due to peripheral vasodilation. Therefore, in dogs the diluent polysorbate 80 is the major cause of severe hypotension resulting from commercial intravenous amiodarone. These studies show that commercial intravenous amiodarone produces results different in dogs than has been previously reported in humans. Therefore: (a) canine models for studying the antiarrhythmic actions of commercial intravenous amiodarone would produce results complicated by severe hypotension; and (b) polysorbate 80 is not an inert substance, but is a potent cardiac depressant.
据报道,市售静脉用胺碘酮具有抗心律失常作用,在人体中仅引起轻度低血压。然而,在狗身上,观察到胺碘酮会导致严重低血压。由于市售静脉用胺碘酮是溶解于含有聚山梨酯80(吐温80)(100毫克/千克)的水中的胺碘酮化合物(50毫克/毫升),因此分别研究了乙醇(5毫克/千克)和聚山梨酯80(10毫克/千克)中胺碘酮的作用,并在麻醉犬中进行了联合研究。市售静脉用胺碘酮和聚山梨酯80可使平均血压和左心室最大dp/dt至少下降60%,持续至少30分钟,而乙醇中的胺碘酮则不会。血压下降主要不是由于外周血管扩张。因此,在狗身上,稀释剂聚山梨酯80是市售静脉用胺碘酮导致严重低血压的主要原因。这些研究表明,市售静脉用胺碘酮在狗身上产生的结果与先前在人体中报道的不同。因此:(a)用于研究市售静脉用胺碘酮抗心律失常作用的犬模型会因严重低血压而使结果复杂化;(b)聚山梨酯80不是惰性物质,而是一种强效心脏抑制剂。