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Biomedical subjects

J Hilsted

Publications and source records attributed to J Hilsted.

At least 91 records · Page 5Linked to original sources

Noradrenaline and isoproterenol kinetics in diabetic patients with and without autonomic neuropathy.

Noradrenaline and isoproterenol kinetics using intravenous infusion of L-3H-NA and of 3H-isoproterenol were investigated in eight Type 1 (insulin-dependent) diabetic patients without neuropathy and in eight Type 1 diabetic patients with autonomic neuropathy matched for age, sex and duration of diabetes. Resting plasma noradrenaline and adrenaline concentrations were reduced in patients with autonomic failure (p less than 0.05). The metabolic clearance rate of noradrenaline was similar in both groups of patients, and the appearance rate of noradrenaline in plasma was reduced in patients with autonomic failure (p less than 0.01). The disappearance of L-3H-noradrenaline from plasma after the infusion of L-3H-noradrenaline had been stopped was not different in patients with and without neuropathy. The metabolic clearance of isoproterenol was not influenced by the presence of autonomic failure and mean values were similar to the corresponding values for noradrenaline. Isoproterenol was only taken up by a non-neuronal uptake; this finding may indicate that neuronal uptake is not important for the inactivation of circulating catecholamines. Alternatively, because the non-neuronal uptake of isoproterenol is probably greater than that of noradrenaline, we cannot exclude the possibility that a small decrease in the neuronal uptake of noradrenaline was compensated for by a slightly higher non-neuronal uptake.

Adult↗

Norepinephrine kinetics during insulin-induced hypoglycemia.

Norepinephrine (NE) kinetics (plasma appearance rate, clearance, and forearm extraction) were measured during insulin-induced hypoglycemia in six healthy subjects. NE clearance did not change during hypoglycemia, indicating that the increase in plasma NE during hypoglycemia is due to an increased plasma appearance rate of NE. Forearm extraction of 3H-NE and of endogenous plasma epinephrine decreased significantly during hypoglycemia, probably due to an increase in regional blood flow.

Adult↗

Changes in plasma volume, in transcapillary escape rate of albumin and in subcutaneous blood flow during hypoglycaemia in man.

Hypoglycaemia was induced by insulin injected intravenously (0.15 i.u./kg body weight) in seven healthy young males. Plasma volume was measured before and during hypoglycaemia by intravenous injection of 125I before hypoglycaemia and of 131I during hypoglycaemia. Plasma volume decreased and transcapillary escape rate increased significantly during hypoglycaemia. Skin temperature and local subcutaneous adipose tissue blood flow were measured in four different regions. Both tended to decrease during hypoglycaemia and decreased significantly 2 h after hypoglycaemia. There was no correlation between changes in the two measurements, suggesting that there is no simple relationship between subcutaneous blood flow and skin temperature during hypoglycaemia.

Adult↗

Plasma clearance of noradrenaline does not change with age in normal subjects.

Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects. Plasma clearance of noradrenaline was identical in the two groups. The increase in plasma noradrenaline concentration, with age, probably reflects an increased sympathetic nervous activity.

Adult↗

The importance of plasma free insulin and counterregulatory hormones for the recovery of blood glucose following hypoglycaemia in type 1 diabetics.

After induction of hypoglycaemia in 31 Type 1 (insulin-dependent) patients, the 10 patients with the slowest recovery of blood glucose from hypoglycaemia were arbitrarily compared with the 10 patients with the fastest recovery of blood glucose. No differences were found between the two groups regarding response of glucagon to hypoglycaemia, whereas the epinephrine (2-fold), norepinephrine (2.4-fold) and cortisol responses were significantly greater in the group with the slow recovery. The plasma free insulin concentrations were higher (2-fold) in the group with slow recovery from 30 min after stop of insulin and throughout the study. This may be explained by a 3-fold greater amount of insulin binding antibodies in this group compared to the group with fast recovery from hypoglycaemia. An inverse significant correlation was demonstrated between the rates of recovery and the amounts of insulin binding antibodies in all the patients (P less than 0.02). This implicates that enhanced counterregulatory hormone responses in the group with the slow recovery from hypoglycaemia could not compensate for the hypoglycaemic effect of a concomitant higher plasma free insulin concentration. Insulin binding antibodies, acting as a depot of circulating insulin, may be a risk factor of prolonged hypoglycaemia in Type 1 diabetics.

Adolescent↗

The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients.

Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short-term, insulin-dependent diabetic patients. The measurements were performed twice within 2 wk, in random order. Continuous subcutaneous insulin infusion (CSII) was applied for 1 wk in order to obtain good control. All eight patients had elevated cardiac output (median 9%) and forearm blood flow (median 34%) during poor compared with good metabolic control, P less than 0.01. In contrast, hepato-splanchnic blood flow was lower (median 12%) during poor compared with good metabolic control, P less than 0.05. Heart rate remained unchanged, while mean arterial blood pressure was slightly higher during poor control, P less than 0.05. Five of six patients had elevated plasma noradrenaline concentration during poor metabolic control. Due to the small number of patients investigated, no valid conclusion regarding the activity of the sympathoadrenal system can be drawn. Our study suggests that both increased cardiac output and reduced hepato-splanchnic blood flow (redistribution) contribute to the elevated blood flow previously demonstrated in various other organs and tissues in diabetic patients during poor metabolic control.

Adult↗

Blood pressure regulation in diabetic autonomic neuropathy.

Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both experimental situations insufficient contraction of resistance vessels has been demonstrated. The vasoconstrictor defects demonstrated are of a magnitude sufficient to account for the prevailing hypotension. Furthermore, during exercise cardiac output is low in patients with autonomic neuropathy, a finding which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions.

Autonomic Nervous System Diseases↗

Haemodynamic changes in insulin-induced hypoglycaemia in normal man.

Haemodynamic variables (plasma volume, heart rate, blood pressure, cardiac output, stroke volume, pulmonary tissue volume, total peripheral vascular resistance, hepato-splanchnic vascular resistance, lower extremity vascular resistance and plasma catecholamines) were measured before and after insulin-induced hypoglycaemia in seven healthy men. Plasma volume decreased significantly at the nadir of glucose (mean decrease 222 +/- 41 ml) and subsequently increased to pre-hypoglycaemic values within 30 min. Cardiac output increased in response to hypoglycaemia (mean increase 2.8 +/- 0.61/min). The early rise in cardiac output was primarily due to an increase in heart rate, but later mainly due to increased stroke volume. Since pulmonary tissue volume was constant, the observed changes in cardiac output are unlikely to be due to a Frank-Starling mechanism but rather to increased sympatho-adrenal activity. Total peripheral vascular resistance as well as lower extremity vascular resistance decreased, whereas hepato-splanchnic vascular resistance was unaffected. Thus insulin-induced hypoglycaemia has marked transient effects on the circulation.

Adult↗

Evaluation of two methods of rapid blood-glucose monitoring by unskilled personnel during surgery.

The accuracy of two rapid methods of blood-glucose monitoring without (Haemo-glucotest 1-44) and with a reflectance meter (Hypocount B) was compared using a laboratory method. The assessment was carried out by personnel with no previous experience in measuring blood glucose. Eighty-five percent of the 92 measurements obtained with the hypocount B were within +/- 20% of the laboratory glucose values. Using haemo-glucotest 1-44 strips, 74% of the readings were within +/- 20% of the reference laboratory values. For values below 5.5 mmol/l, there was a tendency for results to be too low, with 77% of the readings below laboratory values -20%. All situations with severe hypoglycaemia were detected with both strips. The study also demonstrates the ineffectiveness of s.c. insulin regimens during surgery. Only 47% of the measured blood glucose values were within the range of 5.5-10 mmol/l and two of ten patients had hypoglycaemia with values below 2.5 mmol/l. Therefore glucose monitoring during surgery in diabetics seems justified. This monitoring can be performed adequately with strips.

Adult↗

Effects of surgical stress and insulin on cardiovascular function and norepinephrine kinetics.

In resting supine subjects the whole-body clearance of norepinephrine (NE) based on arterial and venous sampling averaged 1.4 and 2.5 liters/min, respectively (P less than 0.02). The difference in clearance values was due to a peripheral uptake of NE averaging 45%. The calculation of plasma NE clearance based on venous sampling results in values that are too high. The plasma appearance rate of NE increased considerably after surgery, whereas the arterial blood pressure remained unchanged. This suggests that the sensitivity to NE is reduced postsurgery. Insulin has certain acute effects on cardiovascular function and plasma NE kinetics that are unrelated to the counterregulatory response to decrements in plasma glucose concentration. Insulin may both induce antagonism to the action of NE and increase the release of NE from sympathetic nerves. Intravenous insulin decreases the plasma volume and increases the hematocrit by an adrenergic mechanism. Plasma NE increases in normal subjects after an oral glucose load. This response may be of importance because in sympathectomized patients both oral glucose and insulin administration decreases the arterial blood pressure. During an oral glucose load insulin-dependent diabetics show abnormalities in the regulation of cardiovascular function and sympathetic nervous activity that may be related to the lack of rise in endogenous insulin in these patients. These results suggest that insulin may be of importance for the normal function of the cardiovascular system.

Adult↗

Testing for autonomic neuropathy.

Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the disease, and may be nonspecific. A number of recently developed quantifiable and reproducible autonomic nerve function tests are reviewed, with emphasis on the physiological basis of the tests and on practical applicability. Finally, diagnostic criteria, based on autonomic nerve function tests, are suggested.

Autonomic Nervous System Diseases↗

Whole body and regional clearances of noradrenaline and adrenaline in man.

The whole body clearance of noradrenaline (NA) was measured in seven patients pre- and postoperatively. L-3H-NA was infused intravenously for 90 min and steady-state concentrations of L-3H-NA were measured in both arterial and peripheral venous blood. Preoperatively, in the resting supine position the clearance values based on arterial and venous sampling averaged 1.4 and 2.5 l/min, respectively (p less than 0.02). The difference in clearance values was due to peripheral uptake of NA averaging 45%. The plasma appearance rate on NA averaged 2.4 nmol/min before surgery and it increased to 9.5 nmol/min postoperatively (p less than 0.02). The plasma clearance of NA did not change. These results indicate that the calculation of plasma NA clearance based on venous sampling results in values that are too high. Furthermore, such values may be influenced by individual variations in the peripheral uptake of NA, since we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase at low work loads and to decrease below resting levels at high exercise intensity. The changes were, however, small (+/- 20% of resting values). The regional extraction ratio of NA was 0.5 to 0.6 in the forearm, the liver and the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma somatostatin increases during hypoglycaemia in insulin-dependent patients with and without B-cell function.

Responses of somatostatin-like immunoreactivity (SLI) to hypoglycaemia were investigated in seven type 1 (insulin-dependent) patients with residual B-cell function, eight patients without B-cell function, and six healthy controls. A higher basal level of SLI was found in the group with B-cell function when compared with the group without B-cell function. The basal level in the normal subjects was in between the two diabetic groups. All the diabetics had a somatostatin response to hypoglycaemia which was independent of residual B-cell function and no different from that of normal subjects.

Adolescent↗