Insulin, growth hormone and corticosteroids in neonatal lambs. Normal concentrations and the effects of gold.
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Biomedical subjects
Publications and source records attributed to G Alexander.
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1. Cardiac output in lambs less than 3 days old was 50-100% higher during summit metabolism than during exposure to thermoneutral conditions.2. The Fick method, based on oxygen consumption, and the dye dilution method for determination of cardiac output, gave qualitatively similar results, but there were considerable quantitative discrepancies.3. The thermogenic tissues, muscle and brown fat, extracted some 80% of the oxygen from the blood perfusing them during summit metabolism.4. Significant right to left shunts through the foramen ovale were detected in about half of the lambs during the first few days of life; the size and incidence of shunts decreased with advancing age but were apparently independent of environmental conditions.5. During exposure to extreme cold, left to right shunts through the ductus arteriosus were detected in a high proportion of lambs, < 12 hr old, with detectable foramen ovale shunts. Pressure measurements in pulmonary and systemic arteries in very young lambs indicated that right to left shunting via the ductus was unlikely to occur; none was detected.6. Summit metabolism was poorly related to oxygen carrying capacity of blood, but significant correlations of summit metabolism with cardiac output (positive) and with oxygen saturation of mixed venous blood (negative) were observed, though not consistently.7. It is concluded that the great variability of summit metabolism between lambs older than 6 hr is not readily explained in terms of cardiovascular phenomena, but that the quantity and efficiency of thermogenic tissues probably play an important role in limiting summit metabolism.
1. Exposure of lambs at sea level to air containing more than 33% oxygen resulted in a small increase in summit metabolism (maximum oxygen consumption on severe cold exposure) in some lambs, and in an improvement in the ability to maintain summit metabolism in others; there was a concomitant improvement in the maintenance of cardiac output, but no change in the degree of right to left shunting.2. Hypoxia (12-13% oxygen in inspired air) reduced summit metabolism of new-born lambs by 25%; but there was no effect in lambs 6-11 days old. Hypoxia neither reduced cardiac output, nor affected the degree of right to left shunting.3. The results suggest that in very young lambs there is some limitation of summit metabolism imposed by the supply of either oxygen or substrate to thermogenic tissues.
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1. Summit metabolism of lambs declined steadily from about 3.5 l. O(2)/kg.hr during the first day of life, to about 2.0 l. O(2)/kg.hr at 2 months of age.2. The contributions of shivering and non-shivering thermogenesis to these changes were estimated by three independent methods; non-shivering thermogenesis was stimulated by catecholamines in a thermoneutral environment, shivering was suppressed by curariform drugs during summit metabolism, and an attempt was made to suppress non-shivering thermogenesis during summit metabolism by use of the sympatholytic drugs phentolamine and propranolol. Drugs were given by intravenous infusion during measurement of oxygen consumption in a closed circuit respiration chamber.3. ;Resting' metabolic rate of lambs during the first day of life was increased two to three-fold, from 1 l. O(2)/kg.hr, by either adrenaline or noradrenaline infused at 1-10 mug/kg.min. The increase declined with increasing age of lamb and was virtually absent by 3 weeks. The response to catecholamines appeared maximal at the dose levels used.4. Muscular paralysis induced by suxamethonium or gallamine reduced summit metabolism by about 2 l. O(2)/kg.hr in all lambs examined within the first 2 months of life. The residual metabolic rate, and the metabolic response to catecholamines under thermoneutral conditions, declined with age in the same manner, and their magnitudes were similar.5. Summit metabolism in lambs aged up to 2 months was depressed to varying degrees by the sympathetic inhibitors phentolamine, propranolol and hexamethonium. The depression with propranolol was greater, and the decline with age clearer, than with phentolamine. Hexamethonium and phentolamine depressed blood pressure, propranolol decreased heart rate and phentolamine and propranolol each suppressed shivering in some experiments.6. In 1 day-old lambs estimates of non-shivering thermogenesis, by the various methods, ranged from 0.8 to 1.4 l. O(2)/kg.hr (mean 1.1 l. or 31% of summit metabolism), and the estimates of shivering ranged from 1.3 to 1.9 l. O(2)/kg.hr (mean 1.6 l. or 46% of summit metabolism). However, in lambs 1-month old, estimates of non-shivering thermogenesis from sympathetic inhibition (0.6 and 0.8 l. O(2)/kg.hr) were considerably higher than estimates from muscular paralysis or stimulation by catecholamines (0.2 and 0.1 l. O(2)/kg.hr). It is suggested that the depression of summit metabolism by the sympathetic inhibitors is not solely due to specific inhibition of non-shivering thermogenesis, at least in the older lambs.7. The possession of a non-shivering thermogenic mechanism in addition to shivering is of clear survival value to new-born lambs.
1. Exposure to cold increased the plasma levels of glucose and lactate in young lambs (< 1-63 days old). Free fatty acid concentrations also increased, the increase being much greater in lambs older than 20 days.2. Intravenous infusions of adrenaline and noradrenaline into lambs under a neutral thermal environment caused large increases in plasma glucose, lactate and free fatty acids.3. Adrenaline and noradrenaline infusions increased the concentration of palmitic, stearic and oleic acids in the plasma of young lambs.4. Treatment of lambs in summit metabolism with either alpha- or beta-adrenergic blocking agents (phentolamine or propranolol, respectively) caused the plasma levels of free fatty acids to fall. Phentolamine hydrochloride decreased the concentration of plasma glucose, but did not change the lactate level. In contrast, propranolol decreased the concentration of both of these metabolites in a significant proportion of the experiments.5. Induction of muscular paralysis by suxamethonium chloride, in lambs exposed to cold, resulted in a rise in plasma free fatty acids, and a fall in glucose and lactate levels.6. These observations suggest that the circulating level of plasma metabolites in young lambs is not the limiting factor in the metabolic response to cold exposure.
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