Establishment of an animal model for Malignant hyperthermia

恶性高热（MH）是麻醉中最危险的并发症之一。它被认为是一种遗传和代谢性肌肉疾病，其综合征是由麻醉剂，去极化神经肌肉阻滞剂及其相关药物引发的。纯种皮特兰猪是一种常见的猪应激综合征（PSS）的动物。PSS可能是一种人类MH的动物模型，本研究从荷兰引进比利时纯种皮特兰猪（Pietrain pig），对其进行培养，以确定其是否为人类NM的动物模型。饲养这些猪，然后通过氟烷吸入试验（halo-test）将其分为PSS阳性（PSS+）或阴性（PSS-）。骨骼肌钙诱导释放速率（CICR）在两个猪种间差异不显著，但均显著高于其它猪种（长白猪-约克夏猪）。所有猪均用氟烷或七氟醚麻醉。在用这些吸入麻醉剂麻醉后，在PSS+或PSS-猪的Pietrain猪中观察到MH综合征。起初PaCO 2升高，此后代谢性酸中毒进展。接着，体温开始升高，随后出现高钾血症、高血清CPK和GOT以及其他酶值升高。结果表明，所有猪在吸入氟烷后100分钟内死亡，其他品系猪均未出现MH综合征，表明皮特兰猪可作为人类MH的动物模型。

Malignant hyperthermia (MH) is one of the most hazardous complications encountered in anesthesia. It is assumed to be a genetic and metabolic disorder of the muscle, whose syndrome is triggered by anesthetics, depolarizing neuromuscular blocking agents and their related agents. The pure-line Pietrain pig is well known all over the world as a species that frequently develops porcine stress syndrome (PSS). PSS may be an animal model of MH observed in man. The purpose of this study was to import and culture the pure-line Pretrain pig and determine whether it is an animal model of human NM or not.The pure-line Pietrain pigs of Belgian were imported from the Netherlands. These pigs were bred and then classified whether positive for PSS (PSS+) or negative (PSS-) by the halothane inhalation test (halo-test). The rate of Ca-induced Ca release (CICR) of skeletal muscle was not significantly deferent between the two pigs, but their values were significantly higher than those of other strains of pigs (Landrace-Yorkshire). All the pigs were anesthetize with halothane or sevoflurane. MH syndrome was observed in Pietrain pigs which were either PSS+ or PSS-pigs following anesthesia with these inhalation anesthetics. PaCO2 was elevated at first and thereafter metabolic acidosis made progressed. Next, body temperature began to rise, followed by hyperkalemia, high serum CPK and GOT, and elevated of other enzyme values. At last, all the pigs died within 100 minutes during halothane inhalation without any therapy, but MH syndrome was not observed in the other strains pigs.We have concluded from these results that Pietrain pigs can be used as an animal model of human MH.