Maccani R M, Wedel D J, Hofer R E
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
Anesth Analg. 1996 Apr;82(4):790-5. doi: 10.1097/00000539-199604000-00020.
Malignant hyperthermia (MH) is a rare genetic trait characterized by potential life-threatening episodes of hypermetabolism, hyperthermia, and muscle rigidity when susceptible humans or animals are exposed to triggering drugs. The role of norepinephrine (NE) in triggering MH is controversial. The purpose of this study was to show that NE does not initiate nor speed the onset of MH in susceptible swine exposed to known triggering drugs. Three groups of MH susceptible (MHS) pigs were exposed to two times the minimum alveolar anesthetic concentrations (MAC) halothane (2%) for 60 min and monitored continuously until a PaCO2 of 70 mm Hg was obtained as an end point for fulminant MH. This dose of halothane is associated with significant hypotension which was addressed by three modalities: no treatment; NE infusion at 8 micrograms.kg-1.min-1; and intraaortic balloon pump (IABP) with 1:1 augmentation (7.0-mL balloon catheter). NE and epinephrine (Epi) plasma levels were determined at 15-min intervals and at trigger time. All animals developed signs of MH during the study. There was no difference in pHa, lactate, PaCO2, or temperature at control or trigger times between groups. Time to trigger was longer in the untreated group compared to both the NE and the IABP groups which were equal. The NE group had greater NE and Epi plasma levels at all times than either the untreated or IABP group and the levels increased at each sample time. The IABP group had increased NE levels at time of trigger compared to control time period, however, Epi levels did not increase. In the untreated group, individual animals had marked increases in NE levels, but extreme variability in response prevented achievement of a single mean change. This group showed no increase in plasma Epi levels throughout the study. There was no difference in NE levels between the untreated and IABP groups. Three animals in the untreated group died prior to trigger due to complications of hypotension. In conclusion, addition of exogenous NE in high doses did not enhance triggering of MH. The large dose NE infusion resulted in increased total catecholamines throughout the study in the NE group with no effect on time to MH trigger compared to animals where mean arterial pressure (MAP) was maintained by IABP. Animals in all three groups with times to trigger of less than 30 min had significantly higher MAPs at control, 15 min, and trigger time than those with times to trigger of greater than 30 min. We conclude that NE does not trigger MH and that severe reduction of MAP delays the the onset of MH in susceptible swine.
恶性高热（MH）是一种罕见的遗传性状，其特征为当易感的人类或动物接触触发药物时，会出现潜在危及生命的代谢亢进、体温过高和肌肉强直发作。去甲肾上腺素（NE）在触发MH中的作用存在争议。本研究的目的是表明，在接触已知触发药物的易感猪中，NE不会引发也不会加速MH的发作。三组MH易感（MHS）猪暴露于两倍最小肺泡麻醉浓度（MAC）的氟烷（2%）中60分钟，并持续监测，直到获得70 mmHg的动脉血二氧化碳分压（PaCO2）作为暴发性MH的终点。该剂量的氟烷会导致显著的低血压，通过三种方式进行处理：不治疗；以8微克·千克-1·分钟-1的速度输注NE；以及使用1:1增强（7.0毫升球囊导管）的主动脉内球囊泵（IABP）。每隔15分钟以及在触发时测定NE和肾上腺素（Epi）的血浆水平。所有动物在研究过程中均出现了MH的体征。各组在对照或触发时的动脉血pH值（pHa）、乳酸、PaCO2或体温均无差异。与NE组和IABP组（二者相同）相比，未治疗组的触发时间更长。NE组在所有时间点的NE和Epi血浆水平均高于未治疗组或IABP组，且在每个采样时间点均升高。与对照时间段相比，IABP组在触发时NE水平升高，但Epi水平未升高。在未治疗组中，个别动物的NE水平显著升高，但反应的极端变异性使得无法获得单一的平均变化值。该组在整个研究过程中血浆Epi水平未升高。未治疗组和IABP组之间的NE水平无差异。未治疗组中有三只动物在触发前因低血压并发症死亡。总之，高剂量添加外源性NE并不会增强MH的触发。与通过IABP维持平均动脉压（MAP）的动物相比，在整个研究过程中，大剂量输注NE导致NE组的总儿茶酚胺增加，但对MH触发时间没有影响。三组中触发时间小于30分钟的动物在对照、15分钟和触发时的MAP显著高于触发时间大于30分钟的动物。我们得出结论，NE不会触发MH，并且MAP的严重降低会延迟易感猪中MH的发作。
