Search PubMed⌕ Search

Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 91 records · Page 5Linked to original sources
PubMed1987

Age and alpha-2 adrenergic regulation of plasma norepinephrine kinetics in humans.

To investigate whether the age-related elevation of plasma norepinephrine (NE) is due to impaired alpha-2 adrenergic inhibition of sympathetic nervous system (SNS) outflow, arterialized plasma NE kinetics were measured before and 120 to 140 min after 1.5 and 5.0 micrograms m/kg oral clonidine in 6 old (57 to 78 years) and 8 young (25 to 39 years) normotensive male volunteers. Baseline plasma NE levels were higher in old compared with young men (M +/- SEM, 355 +/- 58 vs. 197 +/- 22 pg/ml, p less than .02). Clonidine produced significant (p less than .05) dose-related reductions in plasma NE, NE appearance rate, NE clearance, and mean arterial blood pressure (MAP) in both groups. There was no difference between old and young men in response to low dose clonidine. Following the higher dose, both groups had similar suppression of plasma NE (-51 +/- 7% vs. -58 +/- 2%, p greater than .05) and NE appearance (-60 +/- 6% vs. -62 +/- 2%, p greater than .05), but older men had a greater fall in NE clearance (-20 +/- 2% vs. -10 +/- 1%, p less than .003) and MAP (-28 +/- 3% vs. -10 +/- 4%, p less than .006). These findings suggest that sensitivity to alpha-2 receptor-mediated suppression of plasma NE and NE appearance is not diminished in elderly men.

Adult↗
PubMed1987

The role of dietary carbohydrate in the decreased glucose tolerance of the elderly.

In this study we have attempted to evaluate the role of dietary carbohydrate (CHO) in the decreased glucose tolerance of aging. Eighteen healthy young (mean age, 27 +/- 1 standard error of the mean) (SEM) and 18 old (71 +/- 1 SEM) subjects matched for relative weight and socioeconomic group were studied. Oral glucose tolerance tests were performed while eating ad lib diet and after being given high (85%), medium (45%), and low (20% to 30%) CHO formula diets for at least three days. A three- to seven-day food record was used to determine the major nutrients including CHO and fiber intake in the ad lib diet at home. Our older subjects consumed significantly less total calories and slightly less carbohydrate but there was no difference in dietary fiber, protein, and fat intake. When studies were performed on matched CHO diets, decreased glucose tolerance was present in the older group. However, the mechanism(s) involved may vary with dietary CHO and with age. During the low CHO formula diet and the medium CHO ad lib diet, impaired insulin secretion was prominent in the elderly but was not present in the young. During the high CHO formula diet, insulin response was adequate in both old and young, but decreased glucose tolerance persisted in the older group, suggesting that insulin resistance may be the major contributing factor. We conclude that decreased glucose tolerance in the elderly is modified by CHO intake, but is present even when dietary CHO variability is acutely controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Halothane anesthesia does not suppress sympathetic activation produced by neuroglucopenia.

To determine the suitability of halothane anesthesia for studies of sympathetic control of the endocrine pancreas in dogs, we assessed the effect of halothane anesthesia (0.8% inspired concentration) on the sympathetic response to central neuroglucopenia. In dogs anesthetized with halothane, intravenous administration of the neuroglucopenic agent, 2-deoxy-D-glucose (2-DG; 100 mg/kg), produced increases of both systemic plasma epinephrine (EPI; delta = 269 +/- 86 pg/ml, P less than 0.025) and norepinephrine (NE; delta = 157 +/- 55 pg/ml, P less than 0.025) equivalent to those previously observed in conscious dogs. Measurement of plasma NE kinetics revealed that the plasma NE response to 2-DG during halothane was due to an increase in the rate of NE appearance that was identical to that of conscious dogs, rather than to an impairment of NE clearance. In contrast, 2-DG at this dose did not increase plasma EPI or NE levels in dogs anesthetized with pentobarbital sodium (30 mg/kg). Plasma glucose increased modestly after 2-DG (100 mg/kg) in both conscious and halothane-anesthetized dogs but not in the pentobarbital-anesthetized dogs. Although 2-DG at a threefold higher dose (300 mg/kg) caused plasma EPI, NE, and glucose (delta = 12 +/- 3 mg/dl, P less than 0.001) to increase in pentobarbital-anesthetized dogs, the responses to this higher dose of 2-DG were all significantly larger in halothane-anesthetized dogs (delta of plasma glucose = 30 +/- 8 mg/dl, P less than 0.005; P less than 0.0025 vs. pentobarbital).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man.

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Norepinephrine metabolism in humans. Kinetic analysis and model.

The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steady-state NE specific activity in arterialized plasma during [3H]NE infusion and postinfusion plasma disappearance of [3H]NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [3H]NE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P less than 0.01) and upright (r = 0.90-0.98, all P less than 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87 +/- 0.08 vs. 3.25 +/- 0.2 micrograms/min per m2, P less than 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5 +/- 0.6 vs. 4.7 +/- 0.3 liters, P less than 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80 +/- 0.11 vs. 1.21 +/- 0.08 liters/min per m2, P less than 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.

Adult↗
PubMed1987

Functional uncoupling of the platelet alpha 2-adrenergic receptor-adenylate cyclase complex in the elderly.

Elderly humans demonstrate decreased responsiveness in several hormone-receptor systems, including adrenergic receptors. Studies of the beta-adrenergic receptor (beta-AR) system have shown that reduced beta-adrenergic sensitivity in the elderly may be due to reduced beta-AR affinity for agonists. To determine the mechanisms underlying altered alpha-adrenergic sensitivity in the elderly, we assessed the relationships between age and platelet membrane alpha 2-adrenergic receptor (alpha 2-AR)-binding properties, receptor-linked adenylate cyclase (AC) activity, and the affinity of the alpha 2-AR-AC complex for agonists in 18 young (mean age, 24 yr; range 19-34) and 13 elderly (mean age, 69 yr; range, 63-85) normal subjects. In platelet membrane preparations from elderly compared to young subjects, we found similar antagonist-binding properties and similar activity of the catalytic unit of platelet AC, as indicated by the cAMP response to sodium fluoride stimulation. However, mean epinephrine-mediated inhibition of sodium fluoride-stimulated platelet AC activity was less in the elderly [20 +/- 4% (+/- SEM) vs. 31 +/- 2% inhibition; P less than 0.005). In addition, platelet alpha 2-AR affinity for agonist was lower in the elderly, as indicated by the higher concentration of epinephrine needed to inhibit 50% of specific [3H]yohimbine binding (IC50, 3.2 +/- 0.6 vs. 1.4 +/- 0.3 microM; P less than 0.02). These data provide evidence that platelet membranes from elderly humans have decreased responsiveness to alpha-adrenergic stimulation, which can be attributed to reduced alpha 2-AR-AC affinity for agonists. Similarly to reported age-related alterations in beta-adrenergic receptor function, these results suggest that there is also functional uncoupling of the alpha 2-AR-AC complex in elderly humans.

Adenylyl Cyclases↗
PubMed1987

Relationship of islet function to insulin action in human obesity.

To analyze B-cell mechanisms in obesity, we measured the relationship (slope of potentiation) between glucose levels and acute insulin responses (AIR) to isoproterenol or arginine in nondiabetic subjects ranging from lean to markedly obese. Obese men (n = 9) had higher AIRs to isoproterenol than lean men (n = 11) at basal glucose levels [52 +/- 9 (SEM) vs. 32 +/- 5 microU/mL; P less than 0.05], and the difference increased as the ambient glucose level was raised (at 230 mg/dL; 263 +/- 22 vs. 140 +/- 21 microU/mL; P less than 0.0008). The individuals' slopes of glucose potentiation of AIR to isoproterenol were positively correlated with their excess weight (r = 0.72; P less than 0.001). Similar results were found when arginine was used as the secretagogue in other men and in women; the slope of potentiation was positively correlated with excess weight in both men and women (both P less than 0.005), although the effect of excess weight on slope was 51% greater among men (P less than 0.03). An independent measurement of insulin sensitivity (the Bergman SI) was made in the women. The potentiation slope was inversely correlated with SI (P less than 0.0001), indicating that the effect of obesity on insulin secretion is correlated with insulin resistance. These results characterize one mechanism contributing to the hyperinsulinemia of obesity and highlight the importance of considering the prevailing insulin sensitivity when assessing islet function.

Adult↗
PubMed1987

Age differences in the plasma clearance mechanisms for epinephrine and norepinephrine in humans.

There is an age-related increase in plasma norepinephrine (NE) in humans that is due to both an increase in NE appearance into plasma and a decrease in plasma NE clearance. However, previous studies demonstrated no difference in plasma epinephrine (EPI) in young and old subjects, and the effect of aging on plasma EPI appearance and clearance is unclear. To study age differences in basal NE and EPI metabolism we infused eight young (aged 19-26 yr) and eight old (aged 64-74 yr) normal subjects with [3H]NE or [3H]EPI (15 microCi/m2 bolus dose plus 0.35 microCi/m2/min for 50 min) to achieve steady state conditions on separate days. The old subjects had higher arterialized plasma NE levels [mean, 217 +/- 13 (+/- SE) vs. 149 +/- 12 pg/mL; P less than 0.005] and plasma NE appearance. In contrast, neither plasma EPI levels (98 +/- 8 vs. 104 +/- 10 pg/mL; P = NS) nor EPI appearance rates were different in the old and young subjects. The plasma clearance rates of EPI and NE were nearly identical in the young subjects (1.63 +/- 0.14 vs. 166 +/- 0.09 L/min X m2; P = NS). Plasma NE clearance was lower in the old compared to the young subjects (1.38 +/- 0.06 vs. 1.64 +/- 0.10 L/min X m2; P less than 0.05) and was lower than EPI plasma clearance in the same subjects. Although NE and EPI can be removed by both neuronal and nonneuronal uptake mechanisms, and mean plasma clearance values for NE and EPI are the same in the young, the age-related decline in catecholamine clearance is specific for NE. This finding implies a differential effect of age on a catecholamine removal mechanism that is specific for NE.

Adult↗
PubMed1986

Peripheral sympathectomy and adrenal medullectomy do not alter cerebrospinal fluid norepinephrine.

Despite a blood-brain barrier for norepinephrine, the concentration of norepinephrine in plasma and cerebrospinal fluid has been observed to be similar. This relationship between plasma and cerebrospinal fluid norepinephrine levels suggest that peripheral sympathetic neurons innervating blood vessels to brain and spinal cord may contribute significantly to cerebrospinal fluid norepinephrine levels, and questions the validity of cerebrospinal fluid norepinephrine as an index of central nervous system noradrenergic activity. We demonstrate that extensive destruction of the peripheral sympathetic nervous system and the adrenal medulla has no effect on rat cerebrospinal fluid norepinephrine. It is therefore unlikely that peripheral sources of norepinephrine contribute significantly to cerebrospinal fluid norepinephrine levels.

Adrenal Glands↗
PubMed1986

The plasma catecholamine response to ventricular tachycardia induction and external countershock during electrophysiologic testing.

Adrenergic activation during electrophysiologic study could potentially alter the electrophysiologic properties of the arrhythmia substrate. However, the catecholamine response to ventricular tachycardia induction and termination during electrophysiologic testing has to date not been quantitated. Therefore, in 13 patients undergoing electrophysiologic study, arterial plasma norepinephrine and epinephrine were measured before, during and 1, 3, 5, 10 and 15 minutes after ventricular tachycardia induced by programmed stimulation and terminated by a single 100 J external countershock. Sinus rate and the effective refractory period at the right ventricular apex at a basic drive cycle length of 400 ms were measured after the countershock at the same time intervals used for the catecholamine measurements. The mean ventricular tachycardia cycle length (+/- SD) was 187 +/- 30 ms, and the mean duration of ventricular tachycardia was 18 +/- 4 seconds. Plasma norepinephrine and epinephrine increased, respectively, from a baseline of 286 +/- 141 and 119 +/- 40 pg/ml to 770 +/- 330 (169%) and 597 +/- 467 pg/ml (402%), (p less than 0.01) at 1 minute after the countershock. The mean plasma norepinephrine and epinephrine levels during ventricular tachycardia and at times greater than 1 minute after the shock did not differ significantly from baseline levels. Sinus rate increased from a baseline of 74 +/- 13 to 103 +/- 26/min (39%) at 1 minute after the shock (p less than 0.05) and then returned to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Age differences in plasma norepinephrine kinetics in humans.

To determine if the increased plasma norepinephrine (NE) of older individuals is due to greater plasma NE appearance rate and/or decreased NE clearance, arterialized plasma NE kinetics were measured in 25 healthy young (27 +/- 6 yr, M +/- SD) and 18 healthy older volunteers (68 +/- 5 yr) using a tritium-labeled NE isotope dilution technique. Basal NE levels were 54% greater in the older participants (282 +/- 24 vs. 183 +/- 11 pg/ml, M +/- SEM, p less than .001). The mean plasma NE appearance rate was 32% higher (0.33 +/- 0.03 vs. 0.25 +/- 0.02 microgram/m2/min, p less than .016) and NE clearance was 19% lower (1.21 +/- 0.08 vs. 1.49 +/- 0.06 L/min/m2, p less than .006) in the older participants. There was a close correlation between NE appearance rate and NE levels (r = .76, p less than .001, N = 43), but only modest inverse correlation between NE clearance and NE levels (r = -.37, p less than .01, N = 43). Stepwise multiple linear regression analysis revealed that NE appearance rate and clearance explained 80% of the variance in NE levels and that 57% of the variance was attributable to NE appearance, F (1,41) = 54.8, p less than .001, compared with only 14% by NE clearance, F (1, 41) = 6.5, p = .01. We conclude that the principal factor accounting for the higher plasma NE levels of older individuals is an increase in plasma NE appearance rate.

Adult↗
PubMed1986

Plasma catecholamines, dietary carbohydrate, and glucose intolerance: a comparison between young and old men.

Catecholamines play an important role in glucose homeostasis. This study was designed to determine whether circulating catecholamine changes in the elderly play a role in the glucose intolerance of aging and whether these changes are related to dietary carbohydrate intake. Plasma catecholamines (epinephrine and norepinephrine) and glucose were measured before and for 2 h after the administration of 100 g oral glucose in both 18 young (age, 18-39 yr) and 20 old (age, 60-82 yr) normal men during ad libitum home diet and after 3-day weight-maintaining, high or low carbohydrate formula diets in the Clinical Research Center. The elderly men had higher plasma norepinephrine levels before and after oral glucose than the young men even when eating matched formula diets. Plasma epinephrine levels were similar and decreased significantly after oral glucose in both groups. There was no relationship between catecholamine levels and degree of glucose tolerance. A high carbohydrate diet improved glucose tolerance in both old and young subjects. However, changes in dietary carbohydrates were not associated with consistent changes in plasma catecholamines. Therefore, we conclude that 1) glucose intolerance of aging cannot be explained by changes in plasma catecholamines, 2) the age-related increase in plasma norepinephrine is unrelated to dietary carbohydrate intake, and 3) there is no effect of age on suppression of plasma epinephrine after oral glucose administration.

Adolescent↗
PubMed1985

Glucose regulation in non-insulin-dependent diabetes mellitus. Interaction between pancreatic islets and the liver.

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.

Arginine↗
PubMed1985

Effect of a benzodiazepine (alprazolam) on plasma epinephrine and norepinephrine levels during exercise stress.

To determine whether a benzodiazepine central nervous system depressant, alprazolam, inhibits sympathetic discharge during exercise stress, 11 healthy men, aged 21 to 35 years, performed symptom-limited treadmill tests before and on the third day of drug therapy (0.5 mg 3 times daily). Plasma epinephrine and norepinephrine levels were measured at rest and at 8 minutes, 11 minutes and maximal exercise. Owing to catheter malfunction during vigorous exercise, paired samples could be obtained from only 8 subjects at 8 minutes and from only 4 subjects at 11 minutes of exercise. During drug treatment, the plasma epinephrine level was lower at rest (30 +/- 4 vs 53 +/- 7 pg/ml, p less than 0.01), and at 8 minutes (60 +/- 13 vs 117 +/- 19 pg/ml, p less than 0.01), 11 minutes (120 +/- 39 vs 193 +/- 52 pg/ml, p less than 0.05), and maximal exercise (520 +/- 125 vs 970 +/- 324 pg/ml, p = 0.13). Plasma norepinephrine was unchanged at rest (452 +/- 57 vs 413 +/- 45 pg/ml) but lower at 8 minutes (730 +/- 75 vs 886 +/- 82 pg/ml, p less than 0.01), 11 minutes (1,077 +/- 197 vs 1,447 +/- 301 pg/ml, p less than 0.05) and at maximal exercise (3,453 +/- 487 vs 5,590 +/- 1,100 pg/ml, p = 0.09). Exercise duration (17 +/- 1 and 17 +/- 1 minutes) was unchanged on drug. Thus, alprazolam reduces the plasma catecholamine response to exercise stress, possibly by inhibiting centrally mediated sympathetic discharge. Blunting of sympathetic activation may be beneficial in cardiac disorders in which increased sympathetic tone is potentially deleterious.

Adult↗
PubMed1985

Pathophysiology of insulin secretion in diabetes mellitus.

In normal man, glucose serves to regulate basal insulin secretion by its participation with insulin in a feedback loop. In addition, glucose stimulates insulin secretion directly and potentiates insulin responses to nonglucose stimuli such as amino acids, beta-adrenergic stimuli, and gut hormones. Maximal glycemic potentiation of the acute insulin response to IV arginine occurs at a glucose level of approx. 450 mg/dl. In patients with noninsulin dependent diabetes mellitus (NIDDM), basal insulin levels have usually been reported as normal, but if plasma glucose is lowered to normal levels, a deficiency of basal insulin becomes apparent. In addition, the first phase (0-10 min) insulin response to IV glucose is absent in virtually all patients with overt NIDDM. In contrast, the second-phase (greater than 10 min) response is often preserved in NIDDM due to its maintenance by ambient hyperglycemia. Similarly, insulin responses to nonglucose stimuli such as arginine often appear normal in NIDDM because of potentiation by hyperglycemia. However, insulin responses to arginine are lower than those of nondiabetic controls when compared at multiple matched glucose levels. Indeed, maximal potentiation by glucose of the insulin response to arginine is markedly subnormal in NIDDM, suggesting a loss of functional B cell secretory capacity. In patients with long-standing insulin-dependent diabetes mellitus (IDDM), basal insulin secretion and insulin responses to all stimuli are virtually absent. However, in a remission phase, or in IDDM of short duration, basal insulin secretion and insulin responses to nonglucose stimuli may be relatively preserved. Therefore, islet dysfunction in IDDM and NIDDM, while etiologically different, share some common pathophysiological features.

Arginine↗
PubMed1985

Age-related changes in venous catecholamines basally and during epinephrine infusion in man.

Plasma epinephrine (EPI) and norepinephrine (NE) levels were examined among healthy men aged 20 to 25 and 60 to 65 years basally and during EPI infusions. On separate days, 14.3 and 42.9 ng/kg/min EPI was administered intravenously for 45 min. Although there was no age difference in venous EPI levels basally, the old had less increase during the EPI infusions. The plasma metabolic clearance rate of EPI was greater among the old men. Plasma NE levels were elevated among the elderly men, but both age groups had an increase in NE during the EPI 42.9 ng/kg/min infusion rate. During EPI infusions, the old men had less increase in systolic but not diastolic blood pressure or heart rate compared with the young men. The different pattern of change in venous EPI levels and increased metabolic clearance rate of EPI observed among the old men could, in part, explain diminished end-organ responsivity.

Adult↗