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Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 145 records · Page 8Linked to original sources
PubMed1982

Morphine suppresses plasma catecholamine responses to laparotomy but not to 2-deoxyglucose.

The increase of plasma catecholamines that occurs during surgery can be reduced by administration of morphine. To test the hypothesis that morphine specifically blocks nociceptive stimulation during surgery, we compared the effects of morphine administration on the plasma catecholamine response to a laparotomy in pentobarbital-anesthetized dogs with the effect of morphine on the plasma catecholamine response to the neuroglucopenic agent, 2-deoxy-D-glucose (2DG, 300 mg/kg iv). In control dogs, plasma epinephrine (Epi) and plasma norepinephrine (NE) both increased progressively with time following a midline laparotomy (delta Epi by 50 min, +133 +/- 42 pg/ml, P less than 0.01 and delta NE by 50 min, +108 +/- 38 pg/ml, P less than 0.01, mean +/- SE, n = 12). 2-Deoxy-D-glucose produced a similar increase of both plasma NE and Epi. In dogs that received the anesthesia alone, plasma catecholamines did not increase from base line during the experiment. The analgesic morphine (15 mg iv), given 15 min after the completion of laparotomy, not only prevented the progressive rise of plasma catecholamines after laparotomy, but also caused a small but significant decline (P less than 0.05). Naloxone (0.4 mg iv) totally reversed the suppressive effects of morphine, restoring both catecholamines to the levels of their time-related control. In marked contrast, neither morphine nor naloxone affected the plasma NE and Epi increases following the administration of 2DG. These data suggest that morphine suppression of plasma catecholamines during surgery is not due to a generalized attenuation of sympathetic outflow, but rather to a specific interaction with an opiate receptor that either mediates analgesia or lies within the neural pathway stimulated by laparotomy but not by 2DG.

Animals↗
PubMed1982

Cardiac uptake and secretion of catecholamines during adrenergic stimulation in vivo.

Cardiac uptake and secretion of epinephrine (Epi) and norepinephrine (NE) were studied at rest and during the response to systemic vasodilation with dipyridamole in conscious dogs. Chronically implanted catheters in the left atrium and anterior great coronary vein allowed simultaneous measurement of arterial and venous levels of NE and Epi across the segment of myocardium perfused by the left anterior descending coronary artery. Arterial Epi was greater than coronary venous Epi both at rest and during vasodilation. Arterial and venous NE levels were similar at rest. However, arterial NE rose more than venous NE during dipyridamole. Thus, there was net cardiac uptake of NE as well as Epi when systemic plasma catecholamine levels increased in response to vasodilation. Fractional extraction [(A-V)/A X 100)] of Epi by the heart was 50% and was not affected over a sevenfold range of coronary artery flow. Fractional extraction of NE (5-15%) was significantly lower than that of Epi, most likely due to cardiac secretion of NE. Cardiac NE secretion was estimated to increase fourfold during dipyridamole. Thus, cardiac tissue of trained dogs avidly takes up circulating catecholamines. Despite an apparent increase of NE secretion by the heart during the systemic adrenergic response to dipyridamole, the heart remained an organ of net NE uptake and therefore did not contribute to the observed increase of systemic NE levels.

Animals↗
PubMed1982

Glucoregulation during insulin and glucagon deficiency: role of catecholamines.

Glucose production decreases markedly following acute reduction in insulin and glucagon secretion (induced by somatostatin). After about an hour, however, glucose production is restored nearly to basal rates. To study the mechanism by which this occurs, islet hormone deficiency was superimposed on beta-adrenergic blockade. It was found that the hypoglycemia that accompanies insulin and glucagon deficiency is an adequate stimulus for catecholamine secretion. During combined hormone deficiency and beta-blockade, glucose production fell and remained very low for 2-3 h. This resulted in a profound hypoglycemia (glucose less than 30 mg/dl). We conclude from these studies that restoration of glucose production during sustained insulin and glucagon deficiency is not attributable to a) onset of insulin deficiency because insulin is equally depressed in both experimental settings, b) glucose autoregulation even though adequate substrate is available, or c) an alpha-adrenergic mechanism because plasma catecholamines were very high and alpha-receptors were not blocked. Rather, the glucose counterregulation during insulin and glucagon deficiency must be heavily dependent on a beta-adrenergic mechanism.

Adrenergic beta-Antagonists↗
PubMed1982

Hormonal changes and enforced diving in the harbor seal Phoca vitulina. II. Plasma catecholamines.

Plasma epinephrine and norepinephrine concentrations were measured in five harbor seals, Phoca vitulina, during a control period, during a 6-min dive, and during a 30-min postdiving recovery period. Measurements were performed with and without prior glucose administration. Control epinephrine concentrations [189 +/- 118 (SD) pg/ml] and norepinephrine concentrations (340 +/- 191 pg/ml) were similar to resting values in humans. During diving there are dramatic increases in both epinephrine and norepinephrine concentrations, which returned to control values by 30 min of the postdiving recovery period. A similar pattern was found after glucose infusion. The increased catecholamines were not the primary mechanism responsible for arterial constriction during the dive. Persistent diving bradycardia suggests obliteration of the chronotropic effects of catecholamines during the dive. An unchanged stroke volume suggests obliteration of the inotropic effects of catecholamines during the dive. Catecholamines do not appear to be involved in postdiving hyperglycemia and hyperglucogenemia. Neither the regulatory role of increased catecholamines nor the physiological function of increased catecholamines was apparent from the studies. However, dramatic increases in plasma catecholamines during diving appear to be an important component of the hormonal response to prolonged diving in aquatic mammals.

Animals↗
PubMed1982

Sodium salicylate augments the plasma adrenocorticotropin and cortisol responses to insulin hypoglycemia in man.

To test the hypothesis that prostaglandins attenuate neuroendocrine responses to changes in circulating glucose levels in man, we studied the effects of sodium salicylate (SS), a prostaglandin synthesis inhibitor, on the plasma ACTH and cortisol responses to insulin hypoglycemia. Six normal men were given insulin (0.05 U/kg, iv) on 2 different days during the infusion of either SS (40 mg/min) or saline. Compared to the saline control, SS had no significant effect on either the rate of fall of plasma glucose after insulin or the glucose nadir (mean +/- SEM, 33 +/- 3 vs. 36 +/- 3 mg/dl; P = NS). Peak ACTH levels after insulin were higher during SS compared to those during saline in all six subjects (316 +/- 95 vs. 102 +/- 26 pg/ml; P less than 0.05), and SS had a clear effect to increase both the overall ACTH response (F = 21.3; P less than 0.01, by analysis of variance) and the plasma cortisol response (F = 6.72; P less than 0.05, by analysis of variance). The most striking example of this effect of SS occurred in one subject whose peak plasma ACTH was only 44 pg/ml during saline but reached 750 pg/ml during SS despite an identical fall of plasma glucose to 42 mg/dl. Augmentation of the ACTH and cortisol responses to insulin hypoglycemia may be the result of an alteration by SS of recognition of glucose levels by glucose-sensitive cells of the brain, and effect which could be due to the inhibition of prostaglandin synthesis.

Adrenocorticotropic Hormone↗
PubMed1982

The effects of age on the plasma catecholamine response to mental stress in man.

To determine if sympathetic nervous system activity is heightened during psychological stress in older adults, plasma norepinephrine (NE), epinephrine (EPI), heart rate, and blood pressure were measured in 10 healthy old (mean age, 68.5 yr) men and 10 healthy young (mean age, 26.6 yr) men during a 12-min mental stress test. Basal NE was higher in old than in young men (400 +/- 33 vs. 286 +/- 32 pg/ml: p less than 0.01). Consistent significant increases in plasma NE occurred only in the elderly and mean increases (delta) in NE during testing were significantly greater (P less than 0.01) in the old than in the young men. Compared to basal levels, plasma EPI increased by 2 min in both young (delta EPI, 50 +/- 20 pg/ml; P less than 0.02) and old subjects (delta EPI, 41 +/- 11; P less than 0.01) and remained significantly increased throughout the test. There was no difference in either basal or delta EPI between young and old men. Heart rate and blood pressure were significantly increased throughout testing for both age groups. Although the delta blood pressure during testing tended to be greater in the old men, this difference was not statistically significant. Conversely, the delta heart rate was greater in the young subjects (P less than 0.005). Since EPI increases were similar in old and young men, mental stress-related adrenomedullary activation does not appear to change with age. However, the increased plasma NE response in the elderly suggests that they have heightened activity of postganglionic sympathetic neurons during psychological stress.

Adult↗
PubMed1982

Release and clearance rates of epinephrine in man: importance of arterial measurements.

Previous estimates of catecholamine kinetics in human subjects have been based on the measurement of the catecholamine levels in forearm venous plasma. However, the use of forearm venous measurements may introduce considerable error, since venous catecholamine levels may primarily reflect metabolism in the organ drained rather than in the total body. In this study, arterial levels of epinephrine were found to significantly exceed forearm venous levels, both basally (mean +/- SEM, 71 +/- 13 vs. 50 +/- 7 pg/ml; n = 6; P less than 0.05) and during infusions of epinephrine [0.1 microgram/min (112 +/- 9 vs. 77 +/- 11 pg/ml; P less than 0.005) or 2 micrograms/min (862 +/- 71 vs. 437 +/- 66 pg/ml; P less than 0.001)]. During the 2 micrograms/min epinephrine infusion, arterial plasma norepinephrine rose from 191 +/- 37 to 386 +/- 78 pg/ml (P less than 0.001), while venous norepinephrine levels did not change significantly. Fractional extraction (arterial - venous + arterial X 100) of epinephrine across the forearm was 26 +/- 8% in the basal state and increased to 33 +/- 6% and further to 51 +/- 4% during the epinephrine infusions. The addition of propranolol (5 mg, iv, plus an 80 micrograms/min infusion) reduced fractional extraction from 51 +/- 4% to 35 +/- 5%. Whole body clearance of epinephrine, calculated from arterial measurements, was 33 +/- 3 ml/kg . min during the 0.1 microgram/min infusion and 35 +/- 3 ml/kg . min during the 2 micrograms/min epinephrine infusion, values 50% lower than the clearance rates calculated from venous measurements. Propranolol infusion resulted in a fall in whole body clearance to 20 +/- 2 ml/kg . min (P less than 0.001), suggesting that epinephrine clearance is partly dependent on a beta-adrenergic mechanism. Basal endogenous release rate (clearance X basal epinephrine level) was estimated to be approximately 0.18 microgram/min, a value much less than that reported in studies using venous measurements. We conclude that arterial rather than venous measurements should be used to estimate catecholamine kinetics in vivo.

Arteries↗
PubMed1982

Chronic chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose.

To determine the effect of chronic sulfonylurea therapy on islet function in noninsulin-dependent diabetes mellitus (NIDDM), studies were performed in 18 untreated NIDDM patients before and after 12-16 weeks of chlorpropamide therapy. Fasting plasma glucose (FPG) fell with chlorpropamide therapy from 249 +/- 16 to 157 +/- 8 mg/dl (mean +/- SEM; P less than 0.001), and basal insulin increased from 17 +/- 2 to 24 +/- 3 microU/ml (P less than 0.001). The percent change in basal insulin correlated with the pretreatment FPG (r = 0.62; P less than 0.01) and inversely with the change in FPG during chlorpropamide (r = -0.57; P less than 0.025). Thus, patients with the highest pretreatment FPG showed the largest relative increase in basal insulin and the largest fall of FPG with chlorpropamide therapy. In nine patients, arginine-stimulated acute insulin responses (AIR) were studied at each of three plasma glucose (PG) levels both before and during chlorpropamide treatment. AIR at FPG was not different before and during treatment. However, when PG during treatment was matched by glucose infusion to the pretreatment FPG, the AIR was clearly increased during chlorpropamide therapy (176 +/- 65 vs. 49 +/- 11 microU/ml; P less than 0.02). When AIR is plotted against PG for each individual, the slope of the regression line generated (slope of glucose potentiation) is a measure of that patient's islet sensitivity to glucose. The logarithm of the slope of glucose potentiation correlated inversely with FPG (r = -0.92; P less than 0.001). Chlorpropamide treatment increased the slopes of potentiation from 0.26 +/- 0.11 to 1.47 +/- 0.70 (P less than 0.01). We conclude that chronic chlorpropamide therapy augments both basal and stimulated insulin secretion in NIDDM and that this may be an important mechanism of the drug's hypoglycemic effect. The data support the hypothesis that the hyperglycemia of NIDDM is related to islet insensitivity to glucose and that chlorpropamide treatment improves this impairment.

Aged↗
PubMed1982

Arterial plasma epinephrine concentrations and hemodynamic responses after dental injection of local anesthetic with epinephrine.

The effect of dental injection of local anesthetic on arterial plasma epinephrine concentrations and cardiovascular functions was assessed in patients having a maxillary third molar extracted. After three and five minutes, arterial plasma epinephrine concentrations were more than two times higher than baseline values in patients who were given an injection of a standard Carpule (1.8 ml) of 2% lidocaine with 1/100,000 epinephrine (18 micrograms). The heart rate and pressure-rate product increased slightly above baseline control values, and the mean arterial pressure declined slightly (P less than .05) after five minutes. Patients who received an injection of lidocaine alone had no significant change of plasma epinephrine or of the cardiovascular parameters measured. Although the hemodynamic responses to lidocaine plus epinephrine in these healthy young adults were small, the significant increase of systemic plasma epinephrine concentrations suggests that high-risk patients who receive this type of anesthesia should be monitored carefully.

Anesthesia, Dental↗
PubMed1982

Insulin responses to nonglucose stimuli in non-insulin-dependent diabetes mellitus during a tolbutamide infusion.

To determine the effect of tolbutamide on insulin release to nonglucose stimuli in non-insulin-dependent diabetes mellitus and how plasma glucose levels may modulate this effect, the acute insulin response (AIR) to an isoproterenol (12 Micrograms) or an arginine (5 g) i.v. pulse was determined before and during a tolbutamide infusion (7.5 mg/m2/min) in 25 male subjects. During the tolbutamide infusion, there was an increase in the AIR to both isoproterenol (% delta AIR = +49 +/- 21%, N = 11, P less than 0.05) and arginine (% delta AIR = +52 +/- 15%, N = 12, P less than 0.005) and a decrease in plasma glucose (delta plasma glucose for isoproterenol = -24 +/- 6 mg/dl, P less than 0.005; for arginine = -26 +/- 3 mg/dl, P less than 0.001). In separate studies, when the plasma glucose was clamped at baseline values by a variable rate of glucose infusion, there was a greater effect of tolbutamide on AIR when compared with the unclamped tolbutamide studies (isoproterenol: % delta AIR = +132 +/- 25%, P less than 0.025; arginine: % delta AIR = +95 +/- 12%, P less than 0.05). Thus, tolbutamide increases the AIR of nonglucose stimuli, but this augmentation by tolbutamide is blunted by the concomitant decrease in plasma glucose. Consideration of this observation is necessary when interpretating the effects of a sulfonylurea on islet cell responses.

Adult↗
PubMed1982

The effect of chronic sulfonylurea therapy on hepatic glucose production in non-insulin-dependent diabetes.

In 20 patients with untreated non-insulin-dependent diabetes mellitus (NIDDM), there was a positive relationship between fasting plasma glucose (FPG) and glucose production rate, calculated by the isotope dilution technique (r = 0.72, P less than 0.001). This suggests that glucose production rate is an important determinant of FPG in untreated NIDDM. Fifteen patients were also studied during therapy with chlorpropamide for 3-6 mo. During therapy, FPG was lower (133 +/- 9 vs. 216 +/- 20 mg/dl, mean +/- SEM; P less than 0.001), glucose production was lower (59.5 +/- 2.0 vs 77.6 +/- 4.9 mg/m2/min; P less than 0.005), and there was a significant correlation between the fall in glucose production and the fall in FPG (r = 0.59, P less than 0.05). Fasting IRI levels increased in some, but not all, patients during chlorpropamide (untreated 18 +/- 2, treated 21 +/- 2 muU/ml; P= NS). However, there was a significant relationship between the percent rise in IRI and the fall in glucose production during treatment (r = 0.75, P less than 0.001). Patients with a rise in fasting insulin during therapy had a greater fall in glucose production than those whose insulin did not rise (25.4 +/- 8.1 vs. 7.8 +/- 2.4 mg/m2/min; P less than 0.005). When a low-dose insulin infusion was given to approximate the increases of portal venous insulin during therapy, similar falls of glucose production occurred. We conclude that inhibition of endogenous glucose production during chronic chlorpropamide therapy is an important mechanism for the lowering of FPG and that enhanced insulin secretion is the reason for the major part of this inhibition. The small fall in glucose production in those patients whose insulin level did not rise during therapy suggests an additional contribution by some other mechanism.

Adult↗
PubMed1982

Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man.

Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P less than 0.01). Heart rate was increased (P less than 0.0001) and RR variation decreased (P less than 0.05) during beta-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P less than 0.0001). Hence, the cardiac effects of beta-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during beta-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P less than 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P less than 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 +/- 2.8% (x +/- SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during beta-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

Adult↗
PubMed1982

Diabetic neuropathy: a clinical, laboratory and electrodiagnostic study.

The objective of this study was to determine the relationship between nerve conduction velocity (NCV) and hyperglycemia and to assess the extent of NCV changes in adult-onset diabetic patients before and after diabetic treatment. Twenty-five diabetic males (mean age = 50.9 years) were tested twice prior to beginning diabetic treatment. Eighteen of these 25 were also tested at 1, 3, 6, and 12 months after initiation of therapy. Both groups were compared to 23 age-matched controls. Each test session consisted of NCV and clinical sensory and blood chemistry testing. The findings revealed that, before treatment average NCVs of the median, peroneal sural, and tibial nerves and H-reflex latency results were all significantly impaired in diabetic subjects (p less than 0.025). No difference was found between right and left NCVs of the same nerve (p less than 0.05) and NCVs in the lower as well as the upper extremities were significantly reduced (p less than 0.05). Thus, it appears that the neuropathy in these patients was symmetrical and diffuse. Peroneal and median motor nerves showed the greatest amount of NCV slowing when compared to normal values. Furthermore, median, peroneal, and tibial motor NCVs and H-reflex latencies correlated significantly with the degree of hyperglycemia in diabetic subjects before treatment. After initiation of diabetic treatment, median motor NCVs after 1, 3, 6 and 12 months showed significantly improvement when compared to baseline NCV values (all p less than 0.05). Also, the improvement in median NCVs after 3 and 13 months and peroneal NCV after 3 months directly correlated to decreased fasting plasma glucose levels (p less than 0.05).

Adult↗
PubMed1981

The regulation of glucose-induced insulin secretion by pre-stimulus glucose level and tolbutamide in normal man.

The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU.kg-1.min-1 insulin infusion or raised by a 900 mg/min glucose infusion, no effect on first phase insulin secretion (mean delta 3-5 min insulin level) was observed. In contrast, the second phase response (10-60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose or level from the control to that during the insulin or glucose infusion and the change in second phase response (r = 0.65, n = 14, p less than 0.02). The effect of tolbutamide infusion (7 mg.m-2.min-1) when compared with saline control was to increase both first phase (+54 +/- 13 mU/l, n = 8, p less than 0.001, mean +/- SEM) and second phase (+972 +/- 256 mU. min-1.l-1, p less than 0.01) insulin secretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.

Adult↗
PubMed1981

Diabetic neuropathy and plasma glucose control.

Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes.

Animals↗
PubMed1981

Insulin secretion in diabetes mellitus.

A brief review of the normal physiology of insulin secretion is given. The dual role of glucose to directly stimulate insulin release and to potentiate insulin secretion to other islet regulators is emphasized. The B cell of the pancreatic islet is discussed as a metabolic integrator for nutrients, modulated by neural and hormonal input. A feedback model for the normal regulation of glucose concentrations is also described. This model is based on a closed loop between the islet, the liver and peripheral tissues for the production and utilization of glucose. Diabetes mellitus with overt hyperglycemia is characterized by impaired pancreatic B-cell function; however, in noninsulin-dependent diabetic subjects, many aspects of insulin secretion are maintained by a compensatory increase in plasma glucose concentration. The model shows why this increase in plasma glucose occurs and the importance of this hyperglycemia to the restoration of insulin responses to nonglucose secretagogues, second-phase insulin secretion to glucose and basal insulin. The model can account for the usual stability of plasma glucose in noninsulin-dependent diabetes mellitus and the very high glucose levels and lack of glucose stability in insulin-dependent diabetes mellitus. Sulfonylurea drugs increase insulin secretion, but this increase is dependent on the glucose level. Thus, the augmented B-cell function can be masked by a decrease in plasma glucose concentrations. During long-term therapy, the insulin level and responses are unchanged despite lower concentrations of glucose. Therefore, it is hypothesized that sulfonylureas still act by enhancement of B-cell function.

Blood Glucose↗