LIVER METABOLISM DURING MALIGNANT HYPERTHERMIA IN THE PIETRAIN PIG

Liver function was systematically investigated in 7 malignant hyperthermia (MH) susceptible Pietrain pigs (mean weight 67 kg ± 7 kg SEM) to determine the contribution of hepatic metabolism to circulating substrates (Hall, Lucke, Lovell and Lister 1978). It was considered that the progressive lactic acidosis observed in MH may be a result, not only of impaired hepatic uptake of lactate but also production of lactate by the liver as is said to occur in Type II lactic acidosis (Cohen and Simpson 1975). These authors suggested that as the enzyme pyruvate decarboxylase is pH sensitive, and because it is rate limiting in the gluconeugenic pathway of lactate to glucose, under conditions of severe acidosis (pH 7.1) hepatic lactate uptake will be inhibited and there will be production of lactate by the liver. Pigs were prepared with hepatic vein, right ventricle and common carotid artery cannulae. Control measurements were made before inducing MH by ventilating with 1% halothane for 10 minutes together with intravenous injection of 1 mg suxamethonium chloride per kg body weight. Paired arterial and hepatic venous samples were collected at 10 minute intervals for the following estimations: pH, oxygen content, glucose, potassium, lactate, pyruvate, alanine, free fatty acids and glycerol. Hepatic blood flow was estimated by continuous infusion of Indocyanine green (Lucke and Hall 1978). All pigs developed MH with a rise in mean muscle temperature from 37.8°C to 41.5°C after 40 minutes. Mean hepatic blood flow decreased to 25% of control value but, because there was a concomitant increase in oxygen extraction by the liver, hepatic oxygen consumption did not change significantly. At 20 minutes after MH there was a 7-fold increase in glucose efflux from the liver with an arterial glucose concentration of 12.6 mmol/1. There was a massive efflux of 1.1 mmol K+/min early in the response showing that the characteristic hyperkalaemia is not only due to potassium loss from muscle but mainly hepatic in origin. The mean lactate uptake by the liver increased from the control 0.21 mmol/min to 1.19 mmol/min after 10 minutes MH. Even in the presence of gross acidosis (mean pH 6.75) and hepatic blood flow 25% of control, hepatic lactate uptake was still 3 times that recorded in the resting state. It is important to note, however, that although hepatic lactate uptake was increased under these conditions, it was still insufficient in the presence of gross muscle stimulation with a mean arterial lactate concentration of 19.3 mmol/l. It is concluded that the lactic acidosis in porcine MH is due to peripheral overproduction with some impairment of hepatic uptake. The gluconeugenic capacity of the liver was never completely inhibited despite the severity of the metabolic acidosis and hyperthermia and at no stage was there production of lactate by the liver.