Häggendal J, Jönsson L, Johansson G, Bjurström S, Carlsten J
Department of Pharmacology, University of Göteborg, Sweden.
Pharmacol Toxicol. 1988 Oct;63(4):257-61. doi: 10.1111/j.1600-0773.1988.tb00950.x.
Pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males about 6 months old, were exposed to experimental stress. The pigs were either considered normal or shown to be susceptible to develop malignant hyperthermia when tested with halothane at about 6 weeks of age (stress-susceptible pigs). The stress was of the restraint type, produced by two different myorelaxant agents, the depolarizing succinylcholine or the non-depolarizing pancuronium. The blood levels of the catecholamines (CA) noradrenaline (NA) and adrenaline (A) were measured during the stress. The severity of myocardial cell necrosis observed 1 to 2 days after the stress was morphologically graded. In normal pigs the levels of NA during the stress and the degree of myocardial cell necrosis were about the same after both succinylcholine and pancuronium. In stress-susceptible pigs, however, succinylcholine produced very high NA and A levels and severe heart lesions, whereas after pancuronium the NA and A levels were rather low and the heart lesions significantly reduced when compared to those after succinylcholine-induced stress. After pretreatment with dantrolene intravenously the succinylcholine-induced stress only induced slightly increased blood CA levels and no signs of myocardial cell necrosis in pigs susceptible to develop malignant hyperthermia. Dantrolene, an efficient drug in treatment of malignant hyperthermia, probably acts by interfering with release of calcium from the sarcoplasmic reticulum in skeletal muscles. The results indicate that peripheral sympathetic neurones in MHS pigs also react abnormally, probably due to defective calcium turn-over.
选用瑞典长白猪与约克夏猪的杂交后代，6月龄左右的雌性猪和去势雄性猪，使其承受实验性应激。这些猪在约6周龄用氟烷检测时，要么被认为正常，要么显示出易发生恶性高热（应激易感猪）。应激为约束型，由两种不同的肌松剂产生，即去极化的琥珀酰胆碱或非去极化的泮库溴铵。在应激过程中测量儿茶酚胺（CA）、去甲肾上腺素（NA）和肾上腺素（A）的血药浓度。应激后1至2天观察到的心肌细胞坏死严重程度进行形态学分级。在正常猪中，琥珀酰胆碱和泮库溴铵作用后，应激期间的NA水平和心肌细胞坏死程度大致相同。然而，在应激易感猪中，琥珀酰胆碱产生非常高的NA和A水平以及严重的心脏病变，而泮库溴铵作用后，NA和A水平相当低，与琥珀酰胆碱诱导的应激后相比，心脏病变明显减轻。对易发生恶性高热的猪静脉注射丹曲林预处理后，琥珀酰胆碱诱导的应激仅引起血CA水平略有升高，且无心肌细胞坏死迹象。丹曲林是治疗恶性高热的有效药物，可能通过干扰骨骼肌肌浆网中钙的释放起作用。结果表明，恶性高热易感猪的外周交感神经元也有异常反应，可能是由于钙周转缺陷所致。
