Porcine Malignant Hyperthermia. Viii: Leg Metabolism

Abstract

SUMMARYLeg metabolism during porcine malignant hyperthermia (MH) was investigated in eight Pietrain pigs. There was an efflux of glucose, lactate, pynivate and alanine from the leg during MH, demonstrating the occurrence of rapid glycogen degradation. Potassium production by the leg did not change significantly and the decrease in free fatty acid efflux together with the maintenance of grycerol production suggested the utilization of intramuscular triglycerides. The failure of leg blood flow to increase during MH limited the oxygen consumption of the muscle as maximal oxygen extraction occurred early in the response. In a further six Pietrain pigs it was shown that the infusion of sodium nitroprusside increased leg blood flow only slightly. It is possible that the inability of leg blood flow to increase in MH was a result of the decline in cardiac outputThere is surprisingly little information on the contribution of the increase in muscle metabolism during porcine malignant hyperthermia (MH) to the changes observed in circulating metabolites. It is, moreover, not possible to infer the contribution of skeletal muscle by studying changes in central venous metabolite values because of the important and variable effects of hepatic metabolism during MH (Hall et al., 1980). Therefore, in the present study we have systematically examined hind leg metabolism during MH and we have been obliged to use femoral arterial and venous blood samples. A single muscle preparation, such as gracilis in the dog, could not be developed in the pig because of the extremely small size of the peripheral blood vessels and the compact morphology of the leg muscles. A similar technique was used by Gronert and colleagues (Gronert, Milde and Theye, 1976a,b; Gronert and Theye, 1976) to quantify the increased muscle metabolism in MH, but the only substrates measured were lactate and pynivate.The results of the first experiment in the present studies showed that leg blood flow failed to increase to match the marked stimulation of muscle metabolism. Since Williams and colleagues have argued consistently that catecholamine-mediated vasoconstriction is a major factor in the pathogenesis of porcine MH (Williams, Hoech and Roberts, 1978; Williams etal., 1978), we undertook a second experiment to examine the effect of sodium nitroprusside (SNP) on leg blood flow and metabolism during MH. METHODSEight Pietrain pigs (mean weight 60 kg, SEM±2kg) from the Meat Research Institute's herd were studied. Anaesthesia was induced by an injection of thiopentone 10-15 mg kg" 1 through an ear vein. After intubation of the trachea, the lungs were ventilated with 66% nitrous oxide in oxygen using a Cape-Waine ventilator, and anaesthesia was maintained with incremental doses of thiopentone. Twenty-gauge Teflon cannulae, 3 cm long, were placed in both femoral arteries and veins approximately 1 cm distal to the femoral ring and the patency of the cannulae maintained by intermittent flushing with a 0.9% sodium chloride solution. A thermocouple was placed 10 cm deep int...

Thermogenesis in Stress-susceptible Pigs: A Review

“…Metabolic changes occurring during MH have been investigated systematically in pigs (Lucke et al 1976, Hall et al 1980, 1982. It was found from the whole animal studies that there was an increase in oxygen consumption and an even greater increase in carbon dioxide production.…”

“…Within 30 minutes of inducing MH, there was a fall in arterial pH « 6.8) associated with a combined metabolic and respiratory acidosis. By examination of substrate exchange across the liver (Hall et al 1980) and a hind leg (Hall et al 1982), it has been shown that increased hepatic glucose production and a small efflux of glucose from muscle contributed to the hyperglycaemia. Levels of circulating non-esterified fatty acids (NEFA) fell during MH, but a rise in glycerol indicated increased lipolysis.…”