Disordered catecholamine release in pigs susceptible to malignant hyperthermia.
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.
Häggendal
J
J
Department of Pharmacology, University of Göteborg, Sweden.
Jönsson
L
L
Johansson
G
G
Bjurström
S
S
Carlsten
J
J
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D005260:Female; D008297:Male; D008305:Malignant Hyperthermia / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism; D013390:Succinylcholine / Q000494:pharmacology; D013552:Swine
D002395:Catecholamines; D003620:Dantrolene; D013390:Succinylcholine