Differences of post-mortem ATP turnover in skeletal muscle of normal and heterozygote malignant-hyperthermia pigs: Comparison of (31)P-NMR and analytical biochemical measurements.

Energy metabolism of the biceps femoris muscle of normal and heterozygote malignant-hyperthermia pigs was studied post-mortem after in-vivo exposure to a combination of halothane and succinylcholine. The pigs were anaesthetized with halothane and subsequently captive-bolt-stunned immediately after intravenous administration of succinylcholine. Cardiac arrest occurred within one minute after the depolarizing neuromuscular blocking with succinylcholine. During the following 2-5 hours post mortem, the level of several metabolites, reflecting the rate of muscle glycogenolysis and glycolysis, was measured by analytical biochemical techniques and by in situ (31)P-NMR spectroscopy. Both techniques demonstrated more than three-fold-accelerated PCr decay, matched by a similar increase of P(i) in heterozygotes compared with normal pigs. The rate of pH decrease and of lactate accumulation was also three to five times higher in the heterozygotes, all-in-all demonstrating a significantly increased ATP turnover post mortem in these animals when exposed to a combination of halothane and succinylcholine. The results are consistent with the notion of increased excitability of skeletal muscle due to a genetically altered calcium-channel protein. In addition, the results suggest that NMR identification of heterozygote malignant-hyperthermia pigs is possible.