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The effects of the establishment of an adrenergic blockade on suxamethonium-induced porcine malignant hyperthermia (MH) were investigated in Pietrain pigs. Six animals were fed reserpine 10 mg daily for 7 days and then challenged with suxamethonium. Three survived but the remainder developed fatal MH. In a further study of 10 pigs, either phentolamine 40 mug/kg/min or propranolol 50 mug/kg/min were administered for 30 min before suxamethonium stimulation and continued for the duration of the experiment. The five year beta-blocked pigs all became hyperthermic and died whereas the phentolamine-treated group survived. However, both alpha adrenergic blockade and successful reserpinization failed to prevent the abnormal muscle response to the first dose of suxamethonium.

A technique of obtaining muscle biopsies with a liquid nitrogen cryoprobe was used to study intramuscular metabolites in MH-susceptible and unsusceptible pigs. There was no significant difference in muscle metabolite values obtained from susceptible and unsusceptible pigs in the resting state. During MH the changes in metabolites were a result of rapid glycogenolysis and no abnormality of glycolytic control was observed.

The metabolic and endocrine changes in porcine malignant hyperthermia are described and the importance of the catecholamine response emphasised. The relative effectiveness of several different therapeutic agents in the treatment of this syndrome in the Pietrain pig are described and the importance of a common link with the catecholamine response discussed.

The effect of dantrolene on porcine malignant hyperthermia in the Pietrain pig was studied. Five out of six pigs were successfully treated with dantrolene and the alkaline solvent was found to have no therapeutic effect.

The effect of the intravenous administration of dantrolene 3.5 mg/kg body weight on leg metabolism during porcine malignant hyperthermia (MH) was investigated in six Pietrain pigs. Arterial pH improved only slowly after dantrolene and was associated with the continuing efflux of lactate from the leg. Oxygen uptake by the leg had returned to control values 30 minutes after dantrolene. Glucose production by the leg was observed during malignant hyperthermia but this was rapidly abolished by dantrolene. It is concluded that the most useful indices for assessing the adequacy of the treatment of MH are those which reflect changes in oxidative muscle metabolism.

As part of a study of the metabolic effects of long distance riding the results of biochemical analyses of blood samples taken from horses before, immediately after and one hour after an 80 km ride are reported. The results show that the horses were moderately dehydrated, they were working aerobically using fats as metabolic substrates and blood glucose was reduced. There was no evidence of post exercise ketosis and circulating alanine levels fell. Metabolic hormone levels are reported and are related to the availability of substrates for gluconeogenesis. There was evidence of reduced kidney and liver function which was showing little sign of recovery in the first hour after the ride.

Blood samples were taken before and immediately after 80 km and 40 km rides held on consecutive days and analysed for haematocrit, blood glucose and lactate, plasma sodium, potassium, calcium, albumin, free fatty acids (FFA), glycerol, bicarbonate, insulin, cortisol, glucagon, urea, creatinine, uric acid, bilirubin and alkaline phosphatase. Unusually hot weather probably contributed to haemoconcentration with a significant (P < 0.001) increase in haematocrit and plasma albumin. A fall in blood glucose, with a rise in FFA and glycerol were consistent with long distance riding and were associated with a reduction in plasma insulin and a rise in cortisol and glucagon. The results suggested that the horses were working aerobically and the small increase in blood lactate was likely to be a result of reduced tissue perfusion. Plasma urea, creatinine and bilirubin increased during the 80 km ride and were still high the next morning. Blood samples were taken from 2 horses that became exhausted and were forced to retire and the results from these animals indicate the slow rate of recovery. It is suggested that haemoconcentration with reduced tissue perfusion might contribute to exhaustion during long distance exercise and that the speed of recovery might be improved by the intravenous administration of balanced electrolyte solutions.

A technique for anaesthesia of Pietrain pigs using thiopentone or ketamine, ventilation with nitrous oxide and oxygen and muscle relaxation with pancuronium, is described. Bilateral adrenalectomy was carried out by a mid line laparotomy and details of the surgical technique are illustrated. Four of the 10 animals died 7--13 hours after surgery with a hyperthermic response.

Hepatic metabolism during porcine malignant hyperthermia (MH) was investigated in seven Pietrain pigs. The estimated hepatic blood flow decreased during MH, but an increase in oxygen extraction enabled the splanchnic oxygen uptake to be maintained. There was a large release of glucose and potassium from the liver in MH which made an important contribution to the hyperglycaemia and hyperkalaemia. Measurement of hepatic uptake of the precursors of gluconeogenesis, lactate, glycerol and alanine, showed that glucose efflux from liver was derived mainly from glycogenolysis. Lactate uptake by the liver increased during MH, and there was no evidence of hepatic lactate production during the profound acidosis as suggested by in vitro studies with the isolated liver. There was no evidence of major abnormality of hepatic function during porcine MH.

The effects of the administration of noradrenaline alone, and noradrenaline with either phentolamine or propranolol, on thermogenesis and substrate mobilization were investigated in six Pietrain (MH-susceptible) and six Large White (unsusceptible) pigs. The infusion of noradrenaline alone produced a significantly increased lipolytic response and a significantly decreased hyperglycaemic response in Pietrain pigs compared with the Large White breed. Although noradrenaline alone produced only a small increase in body temperature in both breeds, the administration of noradrenaline with propranolol in two Pietrain pigs was associated with the development of fatal hyperthermia. In a further experiment, phenylephrine or isoprenaline was infused into six Pietrain pigs. Three pigs, receiving phenylephrine, became hyperthermic and died, whereas isoprenaline had no effect on body temperature. The results demonstrate the importance of alpha-adrenergic stimulation to heat production in MH-susceptible pigs.

Cardiac output was measured in Pietrain and Large White pigs by the indocyanin green dye dilution method. Ventilation was controlled to ensure adequate oxygenation and normocardia. The cardiac output was lower than recorded by other workers in anaesthetised spontaneously breathing pigs.

The effects of bilateral adrenalectomy, together with the i.v. administration of bretylium tosylate 20 mg kg-1 on halothane-induced malignant hyperthermia (MH), were investigated in six Pietrain pigs. All six animals survived the halothane challenge, and failed to show any signs of increased muscle metabolism. Bilateral adrenalectomy alone prevented halothane-induced MH in three out of four Pietrain pigs, whereas the i.v. administration of bretylium alone protected only one pig out of an additional four animals studied. The results show that complete adrenergic blockade inhibits the susceptibility of Pietrain skeletal muscle to halothane and that the adrenal medulla makes an important contribution to this response.

Blood samples were taken from 15 horses before and after a 50-mile ride to examine the changes occurring in some biochemical constituents. There was a significant (P less than 0.05) decrease in plasma potassium, calcium and magnesium concentrations and a rise in inorganic phosphate but there was no alteration in plasma sodium, chloride or protein levels or change in haematocrit. After the ride there was a highly significant (P less than 0.01) fall in blood glucose corresponding with increased lipolysis and a rise in plasma free fatty acids (P less than 0.001) and glycerol (P less than 0.001). There was a modest increase in blood lactate and a rise in plasma creatine phosphokinase. The results of this preliminary investigation are discussed in relation to the problem of exhaustion in horses during endurance rides.

A technique for implanting a catheter in the hepatic vein of anaesthetised pigs is described. Hepatic blood flow (mean 1100 ml/min +/- 180 ml/min SEM) was estimated by the hepatic uptake of indocyanine green and the oxygen consumption by the liver (mean 62 ml/min +/- 3.4 ml/min SEM) was calculated from the difference in oxygen content between arterial and hepatic venous blood.

In a strain of Pietrain the distance between the vulva and the urethral meatus is greater than that of other breeds of pig. This difference is such that it is difficult to catheterise the bladders of Pietrain gilts since the available specula are either too short in length or too wide in diameter.

Venous blood samples were collected before and immediately after an 80 km ride and a 42 km race. They were analysed for blood glucose and lactate, and for plasma non-esterified fatty acids, insulin, pancreatic glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, somatostatin and vasoactive intestinal polypeptide concentrations. The 80 km ride was associated with marked hypoglycaemia and a slight lactic acidaemia together with an increase in plasma glucagon, somatostatin, pancreatic polypeptide and vasoactive intestinal polypeptide values. The 42 km race produced hyperglycaemia and marked lactic acidaemia together with an increase in plasma glucagon, somatostatin and vasoactive intestinal polypeptide. The increase in these peptides is not related to alterations in blood glucose or the relative contributions of aerobic and anaerobic muscle metabolism. It is suggested that the changes in circulating gut peptides are part of the endocrine response to exercise and the possible physiological role of these changes is discussed.

Porcine malignant hyperthermia was studied in seven Pietrain pigs under standardized experimental conditions. In five animals malignant hyperthermia was triggered with suxamethonium and halothane, but in two pigs suxamethonium alone was used. Characteristic metabolic and physiological changes were found and these are discussed with regard to a possible mechanism to explain the malignant nature of the syndrome.

Blood samples were taken before and after a cross country race over the marathon distance of 42 km. There was a rise in blood glucose and plasma free fatty acids and glycerol associated with a rise in plasma cortisol and glucagon but the fall in insulin was not significant (P > 0.05). Plasma potassium and albumin concentrations increased, calcium decreased and there was no change in sodium or bicarbonate concentrations. There was an increase in plasma urea, creatinine, uric acid, bilirubin and isocitrate dehydrogenase but no change in alkaline phosphatase. There was a rise in plasma creatine kinase. These results of a competitive race are compared with those of the 80 km non-competitive Golden Horseshoe Ride.

The contributions of aerobic and anaerobic muscle metabolism to the heat produced in porcine malignant hyperthermia were studied in seven Pietrain pigs. Oxygen consumption measurements were used to calculate the increase in muscle temperature as a result of aerobic metabolism and this was compared with the observed muscle temperature. The results show that in the initial stage of porcine malignant hyperthermia heat production is largely aerobic in origin. Terminally, aerobic metabolism can account for about half the observed temperature increase.

During general anaesthesia some pigs develop a hyperthermic response which is often fatal. The syndrome is most common in pigs which are susceptible to stress and have a low proportion of body fat. On the basis of an experimental investigation in Pietrain pigs recommendations are presented for the clinical management and treatment of susceptible animals.

The effect of tubocurarine and pancuronium on the initiation or prevention of porcine malignant hyperthermia (MH) was investigated in Pietrain pigs. Tubocurarine 0.6 mg/kg body weight inhibited a suxamethonium-induced response in three pigs, but failed to prevent a fatal halothane-induced response in a further four pigs. Pancuronium 0.2 mg/kg body weight was given to six pigs before a halothane challenge. Three animals developed MH and died; the remainder succembed only after reversal of the neuromuscular blockade. The partial protection afforded by large doses of pancuronium is discussed in relation to the ability of previous muscle activity to influence the sensitivity to halothane.

The toxicity of atracurium has been investigated in subacute tests in rat, dog and monkey, in a fetal toxicity test in the rabbit and in a paranatal study in the cat. No specific adverse effects were found despite administration of supraparalysing doses. It appeared not to cross the placenta at term and the neonatal kitten seemed resistant to its neuromuscular blocking action. In the dog, cat and pig, in which physiological monitoring was undertaken, i.v. injection of three to four times the paralysing dose had little or no effect on arterial pressure or heart rate. The solution did not cause local irritation. Atracurium was not mutagenic in the Ames test.