Wappler F, Roewer N, Köchling A, Scholz J, Steinfath M, Rumberger E, Löscher W, Schulte am Esch J
Abteilung für Anästhesiologie, Universitäts-Krankenhaus Eppendorf, Hamburg.
Anaesthesist. 1995 Aug;44(8):538-44. doi: 10.1007/s001010050186.
In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown that serotonin (5-HT2) receptor agonists can induce MH and "psychotic" behaviour. Both can be prevented by 5-HT2 receptor antagonists. Furthermore, free levels of serotonin in plasma increased concomitantly with clinical and laboratory parameters during halothane-induced MH in pigs. In this study the in vitro-effects of the 5-HT2 receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and normal (MHN) patients. METHODS. Muscle biopsies were obtained from 37 patients aged 5-69 years (23.6 +/- 5.3 years) with clinical suspicion for MH. The patients were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the DOI study. DOI was added to the organ bath in a concentration of 0.02 mmol/l. The in vitro effects on contracture development and muscle twitch were observed for 120 min. RESULTS. Muscle specimens of all patients developed contractures after administration of DOI. However, DOI produced an earlier development of contracture in MHS (17.0 +/- 1.8 min; n = 17) than in MHN (64.7 +/- 5.9 min; n = 15) muscles. In MHS muscles, contractures were more distinct than in MHN muscles; at the end of the experiment, contractures had reached a maximum of 12.5 +/- 0.9 mN in MHS and 5.1 +/- 0.7 mN in MHN muscles. Muscle twitch following DOI administration was reduced significantly in both MHS and MHN muscles. The results of four MHE muscles were comparable with MHS. CONCLUSION. The present study supports the assumption that an altered serotonin system might be involved in the development of MH. In further studies it should investigated whether 5-HT2 receptors of skeletal muscles from MHS subjects are disordered in function or structure. 5-HT2 receptor agonists should be considered as MH-triggering agents.
在对恶性高热（MH）遗传易感的猪中，已表明血清素（5-HT2）受体激动剂可诱发MH和“精神病性”行为。两者均可被5-HT2受体拮抗剂预防。此外，在猪的氟烷诱导的MH期间，血浆中血清素的游离水平与临床和实验室参数同时升高。在本研究中，在MH易感（MHS）和正常（MHN）患者的肌肉标本中研究了5-HT2受体激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷（DOI）的体外效应。方法。从37例年龄在5至69岁（23.6±5.3岁）、临床怀疑患有MH的患者中获取肌肉活检标本。根据欧洲MH方案，首先通过体外挛缩试验（IVCT）将患者分类为MHS、MHN或MHE（MH可疑）。在进行MH分类后，将多余的肌肉标本用于DOI研究。将DOI以0.02 mmol/l的浓度添加到器官浴中。观察120分钟内对挛缩发展和肌肉抽搐的体外效应。结果。所有患者的肌肉标本在给予DOI后均出现挛缩。然而，DOI在MHS肌肉中比在MHN肌肉中更早地引发挛缩（MHS：17.0±1.8分钟；n = 17；MHN：64.7±5.9分钟；n = 15）。在MHS肌肉中，挛缩比在MHN肌肉中更明显；在实验结束时，MHS肌肉中的挛缩最大达到12.5±0.9 mN，MHN肌肉中为5.1±0.7 mN。给予DOI后，MHS和MHN肌肉中的肌肉抽搐均显著降低。四个MHE肌肉的结果与MHS相当。结论。本研究支持血清素系统改变可能参与MH发生发展的假设。在进一步的研究中，应调查MHS受试者骨骼肌的5-HT2受体在功能或结构上是否紊乱。5-HT2受体激动剂应被视为MH触发剂。
