Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane-susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH-susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity.
Richter
A
A
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Gerdes
C
C
Löscher
W
W
D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006221:Halothane; D006720:Homozygote; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics / Q000662:veterinary*; D013552:Swine; D013553:Swine Diseases / Q000235:genetics*
D006221:Halothane