Breeze R G, Laegreid W W, Olcott B M
Br J Pharmacol. 1984 Aug;82(4):809-15. doi: 10.1111/j.1476-5381.1984.tb16477.x.
Rapid infusion of 3-methylindole (3-MI) dissolved in 10% Cremophor EL in water was immediately followed by pulmonary arterial hypertension, systemic arterial hypotension, decreased minute volume and periods of apnoea in goats. Rapid intravenous infusion of Cremophor EL/water alone caused similar immediate effects to those of Cremophor EL plus 3-MI in various dosages. Pretreatment of goats with piperonyl butoxide or phenobarbitone did not significantly alter these immediate cardiopulmonary responses. But pretreatment with piperonyl butoxide prevented clinical signs and pulmonary lesions of 3-MI toxicity, whereas phenobarbitone pretreatment shortened survival time and enhanced pulmonary pathology. Cremophor EL and 3-MI dissolved in Cremophor EL caused severe in vitro haemolysis of caprine and bovine erythrocytes. There was no relationship between the immediate effects of 3-MI and the subsequent development of 3-MI-induced pneumotoxicity and deaths in control goats or in goats pretreated with piperonyl butoxide or phenobarbitone. Induction or inhibition of mixed function oxidase activity had no influence on immediate responses to 3-MI but did change the severity of clinical and pathological responses. It is concluded that there is no apparent relationship between the immediate and the pneumotoxic effects of 3-MI. It is possible that the immediate effects are the result of intravascular haemolysis.
给山羊快速静脉输注溶解于10%聚氧乙烯蓖麻油（Cremophor EL）水溶液中的3 - 甲基吲哚（3 - MI）后，随即出现肺动脉高压、体循环动脉低血压、分钟通气量降低和呼吸暂停期。单独快速静脉输注聚氧乙烯蓖麻油/水溶液在不同剂量下产生的即时效应与聚氧乙烯蓖麻油加3 - MI的效应相似。用胡椒基丁醚或苯巴比妥预处理山羊并没有显著改变这些即时心肺反应。但是用胡椒基丁醚预处理可预防3 - MI毒性的临床症状和肺部病变，而苯巴比妥预处理则缩短了存活时间并加重了肺部病理变化。聚氧乙烯蓖麻油以及溶解于聚氧乙烯蓖麻油中的3 - MI可导致山羊和牛红细胞严重的体外溶血。在对照山羊或用胡椒基丁醚或苯巴比妥预处理的山羊中，3 - MI的即时效应与随后发生的3 - MI诱导的肺毒性和死亡之间没有关系。混合功能氧化酶活性的诱导或抑制对3 - MI的即时反应没有影响，但确实改变了临床和病理反应的严重程度。结论是，3 - MI的即时效应与肺毒性效应之间没有明显关系。即时效应可能是血管内溶血的结果。
