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Biomedical subjects

A V Edwards

Publications and source records attributed to A V Edwards.

119 records · Page 7Linked to original sources

The sensitivity of the hepatic glycogenolytic mechanism ot stimulation of the splanchnic nerves.

1. The sensitivity of the hepatic glycogenolytic mechanism to splanchnic nerve stimulation at relatively low frequencies has been investigated in adrenalectomized calves, dogs and cats.2. In young calves the hyperglycaemic response to splanchnic nerve stimulation at 1.0 c/s for 5 min increased steadily during the first 2 weeks after birth.3. The hyperglycaemic response to splanchnic nerve stimulation for 5 min was directly related to frequency of stimulation within the range 0.5-4.0 c/s in calves tested 2-5 weeks after birth. Pronounced rises in plasma glucose concentration also occurred in calves of this age in response to maximal stimulation (20 c/s) for shorter periods (30 sec) whereas occlusion of the portal vein for the same period produced no comparable effect.4. The effects of splanchnic nerve stimulation for prolonged periods were also investigated in 2- to 5-week-old calves. Under these conditions increased concentrations of glucose in the plasma were maintained for periods of up to 90 min and fell towards the initial values when stimulation was discontinued.5. Prolonged stimulation of the peripheral ends of both splanchnic nerves at either 2.0 or 4.0 c/s produced a transient reversal of hypoglycaemia in calves pretreated with large doses of insulin; both the extent and duration of these responses were related to frequency of stimulation.6. The hyperglycaemic response to bilateral splanchnic nerve stimulation was directly related to frequency of stimulation within the range 0.5-4.0 c/s in adrenalectomized dogs. Comparable responses were obtained in adrenalectomized cats in response to stimulation at 2.0 c/s, but stimulation at 1.0 c/s produced no rise in mean plasma glucose concentration in these animals.7. The sensitivity of the hepatic glycogenolytic mechanism has been assessed in relation to the associated changes in haematocrit and mean aortic blood pressure under the same conditions.8. The results of these experiments support the contention that tonic changes in sympathetic efferent activity are associated with variations in the rate at which glucose is released from the liver under physiological conditions.

Adrenalectomy↗

The hyperglycaemic response to stimulation of the hepatic sympathetic innervation in adrenalectomized cats and dogs.

1. The extent to which the hyperglaemic and glycogenolytic responses to splanchnic nerve stimulation depend upon the integrity of the hepatic innervation has been investigated in adrenalectomized dogs and cats.2. In both species maximal stimulation of the hepatic nerves (20 c/s) produced changes in plasma glucose concentration comparable to those which have been found to occur in response to bilateral splanchnic nerve stimulation at the same frequency. Furthermore, the hyperglycaemic response to splanchnic nerve stimulation was very substantially reduced by section of the hepatic nerves, whereas the associated changes in haematocrit and mean aortic blood pressure were not significantly altered.3. Comparison of the changes in plasma glucose concentration in response to splanchnic or hepatic nerve stimulation at relatively low frequencies (1.0-2.0 c/s) showed that stimulation of either nerve produced closely similar responses in adrenalectomized animals of both species.4. In adrenalectomized dogs maximal stimulation of the hepatic nerves (20 c/s) for shorter periods (30 sec) caused a significant rise in plasma glucose concentration whereas total occlusion of the portal vein for the same period in the same animals produced no statistically significant hyperglycaemic effect.5. Maximal stimulation of the hepatic nerves (20 c/s) caused a rapid rise in plasma glucose concentration in hypoglycaemic adrenalectomized cats pretreated with a large dose of insulin (4 u./kg body wt.).6. It is concluded that the hyperglycaemic response to stimulation of the peripheral ends of the splanchnic nerves in adrenalectomized dogs and cats is directly dependent upon activation of sympathetic efferent fibres to the liver.

Adrenalectomy↗

Comparison of the hyperglycaemic and glycogenolytic responses to catecholamines with those to stimulation of the hepatic sympathetic innervation in the dog.

1. The effects of stimulation of the splanchnic innervation to the adrenal medullae, in dogs with cut hepatic nerves, were compared with those obtained previously in response to splanchnic and hepatic nerve stimulation in adrenalectomized dogs.2. Maximal stimulation of both adrenal medullae via the splanchnic innervation (20 c/s for 9 min), in dogs with cut hepatic nerves, produced closely similar hyperglycaemic and glycogenolytic responses to those obtained previously in adrenalectomized dogs with intact hepatic nerves.3. The rise in plasma glucose concentration in response to maximal stimulation of the adrenal medullae in dogs with intact hepatic nerves was found to be comparable to that which occurs in response to maximal stimulation of the hepatic sympathetic innervation alone. In contrast, the rise in haematocrit during maximal stimulation of the entire splanchnic innervation was substantially greater than that observed after removal of both adrenal glands.4. The output of adrenaline and noradrenaline from the left adrenal gland was determined during maximal stimulation of the left splanchnic nerve (20 c/s for 9 min). These results were then used to compute doses of the two amines which would reproduce the output of catecholamines from both glands under such conditions. The extent of the rise in mean plasma glucose concentration in response to these infusions was similar to that produced by maximal stimulation of both adrenal glands, but the duration of hyperglycaemia and depletion of liver glycogen were significantly less.5. Stimulation of the splanchnic innervation was found to produce an initial ;surge' in the release of catecholamines from the adrenal medullae, followed by a rapid decline in output when stimulation was continued for longer than 30 sec. Evidence was obtained which showed that this pattern of release is well suited to produce rapid mobilization of liver glycogen.6. Comparable changes in plasma glucose concentration occurred in response to stimulation of either the adrenal medullae or the sympathetic innervation to the liver at low frequency (2.0 c/s for 5 min). Stimulation of both pathways simultaneously, at the same frequency, produced smaller responses.7. Intramesenteric infusions of noradrenaline at 1.0 mug.kg(-1) min(-1) for 5 min produced comparable changes in plasma glucose concentration to those observed during stimulation of either pathway alone at low frequency. The mean plasma noradrenaline concentration of portal blood was raised by between 92 and 105 ng/ml. during these infusions.8. It is concluded that stimulation of either the splanchnic innervation to the liver, or of both adrenal medullae, at high frequency (20 c/s for 9 min) represents a supramaximal stimulus for hepatic glycogenolysis. Comparison of the responses to stimulation at low frequency (2.0 c/s for 5 min) suggests that the hepatic glycogenolytic mechanism is equally sensitive to stimulation via either route in this species.

Adrenal Glands↗

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves, sheep, dogs, cats and pigs.

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in calves, sheep, dogs, cats and pigs after removal of both adrenal glands.2. Stimulation of both splanchnic nerves produced comparable hyperglycaemic and glycogenolytic effects in sheep, dogs and cats; the mean liver glycogen concentration was reduced by between 7.0 and 10.5 mg/g, five min after stimulation was discontinued, at which time the mean plasma glucose concentration had risen by between 126 and 137 mg/100 ml.3. In five 3-5 week-old calves which were tested under identical conditions the mean liver glycogen concentration was reduced by 13.3 +/- 1.9 mg/g and the plasma glucose concentration raised by 216 +/- 1.9 mg/100 ml., 5 min after stimulation was terminated.4. In pigs, stimulation of both splanchnic nerves invariably produced a rise in the plasma glucose concentration, even when the concentration of glycogen in the liver was less than 5 mg/g before stimulation. The response was, nevertheless, considerably smaller in these animals than in any of the other species investigated.5. Splanchnic nerve stimulation also caused a rise in mean aortic blood pressure and blood haematocrit during the period of stimulation; changes of approximately the same order of magnitude were encountered in all five species.6. Dogs were found to resemble calves in that the hyperglycaemic response to stimulation of a single splanchnic nerve did not differ significantly from that obtained when both were stimulated simultaneously; furthermore, either nerve was found to be equally effective.7. In cats the change in plasma glucose concentration in response to stimulation of a single splanchnic nerve was always less than that which occurred in response to bilateral stimulation although comparable changes in blood haematocrit occurred in both groups of animals.8. It is concluded that stimulation of the splanchnic nerves causes break-down of glycogen in the livers of various unrelated species of adult animals but that the magnitude of the hyperglycaemic response in the young calf provides further evidence of the importance of the sympathetic system in the control of metabolism in the young animal.

Adrenalectomy↗

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves.

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in adrenalectomized calves at different ages.2. During the first 24 hr after birth unilateral splanchnic nerve stimulation led to a prompt rise in the plasma glucose concentration and this response was more than doubled when both nerves were stimulated simultaneously. Under these latter conditions hyperglycaemia was found to be associated with a measurable loss of glycogen from the liver.3. Both the glycogenolytic and hyperglycaemic effects of splanchnic stimulation became more pronounced with age; at 5 weeks of age liver glycogen was depleted by approximately 2/3 and plasma glucose raised by about 200 mg/100 ml. after stimulation of the right splanchnic nerve for 9 min.4. Splanchnic stimulation also caused a rise in mean arterial blood pressure and haematocrit during the period of stimulation at all ages studied; the rise in haematocrit was greatest in the oldest animals.5. The hyperglycaemic response to splanchnic stimulation persisted after pancreatectomy and was also demonstrated in calves in which the whole of the portal effluent blood flow was collected during splanchnic stimulation. The plasma from blood collected in this way had no apparent hyperglycaemic effect when infused into a branch of the mesenteric vein in recipient calves.6. In adrenalectomized calves in which the liver had been partially denervated before stimulation both the hyperglycaemic and the glycogenolytic responses were substantially reduced, although the rise in haematocrit was unaffected, during stimulation of both splanchnic nerves.7. It is concluded that glycogenolysis occurs in the liver as a result of stimulation via the hepatic innervation in the new-born calf and that this response increases with age during the first few weeks after birth.

Adrenal Glands↗

The effects of insulin of the new-born calf.

1. The normal variations in the concentrations of glucose, fructose and lactic acid in the blood of the calf which occur during the first few weeks after birth have been examined.2. The responses of calves of different ages to intravenous injections of insulin have been examined by recording both the incidence of convulsions and the changes in the concentration of glucose, fructose and lactic acid in the blood.3. New-born calves rarely convulsed during prolonged and severe hypoglycaemia and, if convulsions occurred, the onset was delayed by 6-8 hr. At 7 days of age convulsions usually followed the injection of insulin within 1(1/2)-2 hr.4. No relationship could be found between the duration of hypoglycaemia and the incidence of convulsions at different ages. Hypoglycaemia was most prolonged in new-born calves which rarely convulsed.5. Insulin hypoglycaemia during the first 24 hr after birth was associated with a rise in the concentration of lactate in the blood. Similar changes did not occur in calves at 7 days of age, in which the incidence of convulsions was much higher, or in weaned animals.6. After both splanchnic nerves had been cut, insulin always caused convulsions in 24-hr-old calves. There was no rise in the blood lactate concentration in these animals.7. Intravenous infusions of adrenaline but not noradrenaline in amounts similar to those known to be released from the adrenal medulla of the calf of this age prevented convulsions in 24-hr-old calves after section of the splanchnic nerves. These infusions had little effect on the blood glucose concentration but caused a similar rise in the lactic acid concentration to that found in normal animals at this age during hypoglycaemia.8. At 7 days of age convulsions could only be prevented during hypoglycaemia by infusing larger doses of adrenaline which significantly raised the blood glucose concentration. The increase in the blood lactate concentration was less than that in the new-born animals.9. The resistance to insulin hypoglycaemia which occurs immediately after birth is transient; it depends upon the release of adrenaline from the adrenal medulla and is associated with high concentrations of lactate in the blood during hypoglycaemia.

Age Factors↗