Fukushima K, Watanabe K, Kikuya T, Satoh T, Uchida K, Nagashima H
Masui. 1989 May;38(5):654-60.
It is well established that a large dose of atracurium (more than twice ED95) produces significant release of histamine in the blood accompanying hypotension but recovery to control level within a few minutes after the administration of atracurium. We speculated that laudanosine, a metabolite of atracurium may play an important role in preventing this cardiovascular disaster due to histamine release. From this concept, we investigated the effect of laudanosine on the release of epinephrine and norepinephrine in dogs, anesthetized with halothane, nitrous oxide and oxygen. Two different doses of laudanosine (1 microgram.kg-1 and 10 micrograms.kg-1) were selected and serum catecholamine levels were measured with HPLC in six dogs. Intravenous injection of 1.0 microgram.kg-1 laudanosine increased NE level from 0.11 +/- 0.03ng.ml-1 to 0.13 +/- 0.04ng.ml-1 at 3 minutes after the injection. Blood pressure, heart rate, pulmonary arterial pressure, pulmonary wedge pressure and central venous pressure did not change significantly. The intravenous injection of 10 micrograms.kg-1 laudanosine increased NE level from 0.09 +/- 0.02ng.ml-1 to 0.14 +/- 0.02ng.ml-1 at 1 minutes after the injection, but there was no remarkable cardiovascular effect. From this study we conclude that the intravenous injection of laudanosine increased serum NE level, but there was no significant hemodynamic change in the dogs.
大量研究证实，大剂量阿曲库铵（超过ED95的两倍）会导致血液中组胺大量释放，同时伴有低血压，但在注射阿曲库铵后几分钟内会恢复到对照水平。我们推测，阿曲库铵的代谢产物劳丹诺辛可能在预防因组胺释放引起的心血管灾难中起重要作用。基于这一概念，我们研究了劳丹诺辛对用氟烷、氧化亚氮和氧气麻醉的犬肾上腺素和去甲肾上腺素释放的影响。选择两种不同剂量的劳丹诺辛（1微克·千克-1和10微克·千克-1），并通过高效液相色谱法测量六只犬的血清儿茶酚胺水平。静脉注射1.0微克·千克-1劳丹诺辛后3分钟，去甲肾上腺素水平从0.11±0.03纳克·毫升-1升高至0.13±0.04纳克·毫升-1。血压、心率、肺动脉压、肺楔压和中心静脉压均无明显变化。静脉注射10微克·千克-1劳丹诺辛后1分钟，去甲肾上腺素水平从0.09±0.02纳克·毫升-1升高至0.14±0.02纳克·毫升-1，但未观察到明显的心血管效应。从这项研究中我们得出结论，静脉注射劳丹诺辛可使犬血清去甲肾上腺素水平升高，但未引起明显的血流动力学变化。
