Biomedical subjects
Publications and source records attributed to G M Hall.
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.
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.
I. Two experiments were done with Pietrain and Large White pigs (about 50 kg body-weight) to determine whether fat mobilization is enhanced in the stress-sensitive Pietrains (which also produce pale, soft, exudative (PSE) meat). 2. In Expt I, plasma glucose and insulin concentrations and free fatty acid (FFA) concentrations and composition were measured in five Pietrains and five Large Whites after feeding, during an infusion of norepinephrine (2.5 microng/kg body-weight per min), 16 and 21 h after the withdrawal of food and following insulin administration (0.3 IU/kg body-weight). The entry rate of oleic acid was measured 4 h after feeding. Body composition and longissimus dorsi pH measurements were made on killing the pigs 4 d after the experiment. 3. After feeding, the Pietrans tended to have lower concentrations of glucose and insulin in plasma compared with the Large Whites, and higher concentrations of FFA. The Pietrans also had a faster entry rate of oleic acid into body tissues. In fasting (16 h) these differences in hormone and metabolite concentrations were also present and relationships between them and body development could be detected. Pietrains had higher concentrations of FFA and lower concentrations of insulin than Large Whites at a particular stage of the development of fat and muscle (subcutaneous fat weight divided by longissimus muscle weight). 4. The fatty acid composition of FFA resembled that of the backfat triglycerides in fasting and during norepinephrine infusion but not in the fed state. In particular the proportion of fatty acid 18:I was low in the fed pigs and that of 18:2 was high. The contrast in FFA composition between the fed and stimulated state was greater in the Large Whites. 5. The Pietrains were less sensitive to the antilipolytic action of insulin. Glucose and FFA concentrations were similar in both breeds during the norepinephrine infusion although insulin concentrations were increased to a larger extent in Large Whites at the termination of the infusion. 6. In Expt 2, anaesthetized Pietrain and Large White pigs were given constant infusions of norepinephrine alone (2.5 microng/kg body-weight per min) and norepinephrine + propranolol (2, 10 and 20 microng/kg body-weight per min) or phentolamine (2 and 10 microng/kg body-weight per min). The aim was to determine whether the breeds differed in their sensitivity to norepinephrine when conscious responses to the hormone were prevented. 7. When norepinephrine alone was infused, fat mobilization was greater in the Pietrain pigs and glucose concentrations were greater in the Large Whites. Propranolol markedly reduced the lipolytic action of norepinephrine, particularly in the Pietrain pigs studied, and phentolamine reduced its glycogenolytic action, particularly in the Large White pig. 8...
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.
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.
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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.
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.
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.
The continuous administration of nitrous oxide, in subjects who remain conscious, caused only a relatively small increase in the threshold of appreciation of pain, induced experimentally by tibial pressure and a hot wire applied to the thenar eminence. The threshold reached a maximum at 10 min. A concentration of 50% nitrous oxide caused only a marginally greater effect than 33%. In some subjects pain thresholds returned to control values during administration of the gas. In contrast, when a concentration of 50% nitrous oxide was approached in step changes of 7-10% over a period of 45 min, the effect on the pain threshold was more than doubled. It was concluded that, with respect to analgesia, adaptation of the nervous system to a constant concentration of nitrous oxide can occur in some subjects.
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.
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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.
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