Hypertonic saline infusion induces panic in patients with panic disorder.
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Adult↗
Biomedical subjects
R C Veith
Publications and source records attributed to R C Veith.
Influence of sympathetic stimulation and parasympathetic withdrawal on Doppler echocardiographic left ventricular diastolic filling velocities in young normal subjects.
To determine the effects of parasympathetic withdrawal or sympathetic stimulation on Doppler echocardiographic measures of left ventricular diastolic filling, we studied 10 young normal subjects aged 21 to 29 years during separate infusions of atropine (0.8 mg followed by 0.4 mg every 10 minutes until heart rate greater than 110 beats/min or a total dose of 2 mg was attained) and epinephrine (10, 25 and 50 ng/kg/min for 12 minutes each). At the highest atropine dose, heart rate increased from 60 +/- 9 to 105 +/- 8 beats/min (mean +/- standard deviation), the diastolic filling period decreased by 61% (573 +/- 141 to 222 +/- 34 ms), the peak early (E) filling decreased 23% (77 +/- 12 to 61 +/- 11 cm/s), the peak atrial (A) filling increased 103% (40 +/- 6 to 81 +/- 17 cm/s), and the E/A ratio decreased by 60% (2.0 +/- 0.5 to 0.8 +/- 0.3) (all p less than 0.001). These alterations were not correlated to changes in systolic function, preload, blood pressure or plasma catecholamines, all of which were unchanged. However, atropine-induced changes in diastolic filling period were highly correlated to changes in E peak (r = 0.64, p less than 0.01), A peak (r = -0.95, p less than 0.001) and the E/A ratio (r = 0.93, p less than 0.001). The effects of atropine on the E/A ratio were normalized by dividing the E/A ratio by the diastolic filling period (E/A/diastolic filling period).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The relation between radionuclide angiography and Doppler echocardiography during contractile changes with infusions of epinephrine.
To define the quantitative relations between radionuclide and Doppler measures of systole during sympathetic activation with epinephrine, 10 young normal men were studied with simultaneous radionuclide angiography and M-mode and Doppler echocardiography during graded infusions of epinephrine (10, 25 and 50 ng/kg/min for 12 minutes each). During a nine-fold increase in circulating levels of epinephrine in arterialized plasma (94 +/- 59 to 879 +/- 310 pg/ml, P less than 0.001), the heart rate increased from 58 +/- 8 to 73 +/- 7 beats/min (P less than 0.01), whereas the mean arterial pressure fell from 82 +/- 3 to 75 +/- 6 mmHg (NS) and end-systolic wall stress decreased from 97 +/- 6 to 67 +/- 10 dynes/sec (P less than 0.01). The ejection fraction as estimated using radionuclide techniques increased from 68 +/- 6 to 83 +/- 6%, the peak ejection rate measured in this way increased from -3.36 +/- 0.3 to -5.10 +/- 0.5 end-diastolic volumes/sec, the ejection fraction as estimated with M-mode echocardiography increased from 66 +/- 5 to 83 +/- 5%, the echocardiographic ventricular dimension shortening increased from -1.78 +/- 0.2 to -2.7 +/- 0.4 sec-1, the peak aortic outflow velocity as measured with Doppler techniques increased from 98 +/- 13 to 147 +/- 25 cm/sec, and the aortic outflow acceleration velocity increased from 11 +/- 3 to 27 +/- 7 m/sec2 (all P less than 0.001). There was a significant correlation between the changes in radionuclide and M-mode estimations of ejection fractions (r = 0.82), between the radionuclide peak ejection rate and M-mode peak dimension shortening (r = 0.80) and between the radionuclide peak ejection rate and the Doppler peak aortic outflow velocity (r = 0.90) (all P less than 0.01). We conclude that corresponding radionuclide and Doppler echocardiographic measurements of systolic function are altered similarly during increased sympathetic activation with epinephrine.
Adult↗
Imipramine in the treatment of depressed Alzheimer's patients: impact on cognition.
A double-blind study evaluated the impact of imipramine on cognitive function in 61 patients with Alzheimer's disease. Twenty-eight patients had coexistent depression and dementia; 33 had dementia only. All were randomly assigned to an 8-week trial of imipramine or placebo. For both depressed and nondepressed subjects, the effect of imipramine on cognition was minimal. A subtle decrement in general cognitive function was evident in those treated with imipramine, as compared with those treated with placebo. No effects were observed on memory. Clinicians are advised that very low doses of imipramine (25 mg/daily) may be tolerated in depressed Alzheimer patients, but that cognitive changes do occur in some patients and should be carefully monitored.
Aged↗
Effects of yohimbine on human sympathetic nervous system function.
The alpha 2-adrenergic receptor antagonist yohimbine is often used as a neuroendocrine probe in human studies, in which it is assumed to increase plasma norepinephrine (NE) by increasing sympathetic outflow. In this study we have tested that assumption by using a radioisotope dilution technique to measure norepinephrine (NE) kinetics in arterialized plasma after administration of oral yohimbine (20 or 40 mg) or placebo to normal young men. In agreement with previous studies, we found that yohimbine causes dose-dependent increases in blood pressure, heart rate, and plasma NE. We further found that the increase in plasma NE is, in fact, due to an increase in the rate of appearance of NE into plasma and not to reduced NE clearance from plasma. In addition, we found that yohimbine causes a dose-dependent increase in plasma epinephrine, which had not been found in studies measuring catecholamines in venous plasma. We conclude that yohimbine increases plasma NE levels by increasing the rate of NE release from sympathetic nerves, and probably increases epinephrine release from the adrenals.
Administration, Oral↗
Role for autonomic nervous system to increase pancreatic glucagon secretion during marked insulin-induced hypoglycemia in dogs.
To determine the role of the autonomic nervous system (ANS) in mediating the glucagon response to marked insulin-induced hypoglycemia in dogs, we measured arterial and pancreatic venous glucagon responses to insulin-induced hypoglycemia during acute, terminal experiments in halothane-anesthetized dogs in which the ANS was intact (control; n = 9), pharmacologically blocked by the nicotinic ganglionic antagonist hexamethonium (n = 6), or surgically ablated by cervical vagotomy and cervical spinal cord section (n = 6). In control dogs, insulin injection caused plasma glucose to fall by 4.4 +/- 0.2 mM to a nadir of 1.7 +/- 0.2 mM. Arterial epinephrine (EPI) levels increased by 13,980 +/- 1860 pM (P less than 0.005), confirming marked activation of the ANS. Pancreatic output of glucagon increased from 0.53 +/- 0.12 to 2.04 +/- 0.38 ng/min during hypoglycemia (change [delta] +1.51 +/- 0.33 ng/min, P less than 0.005). This increased arterial plasma glucagon from 27 +/- 3 to 80 +/- 15 ng/L (delta +52 +/- 14 ng/L, P less than 0.025). Hexamethonium markedly reduced the ANS response to insulin injection (delta EPI +2130 +/- 600 pM, P less than 0.025 vs. control) despite a similar fall of plasma glucose (delta -4.1 +/- 0.2 mM) and a lower nadir (0.6 +/- 0.1 mM). Both the pancreatic glucagon response (delta glucagon output +0.45 +/- 0.2 ng/min) and the arterial immunoreactive glucagon response (delta +5 +/- 4 ng/L) were substantially reduced by hexamethonium (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy.
To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/- 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity.
Aged↗
Autonomic responses to stress in Vietnam combat veterans with posttraumatic stress disorder.
This study tested the hypothesis that combat veterans with posttraumatic stress disorder (PTSD) experience sympathetic nervous system activation in response to war-related laboratory stimuli. Circulating plasma catecholamines, vital signs, and affect ratings were measured in 10 Vietnam combat veterans with PTSD and 11 control subjects, during and after viewing combat and noncombat stress films. PTSD subjects responded more strongly than controls to the combat film, with greater increases in plasma epinephrine, pulse, blood pressure, and subjective distress. The increases in autonomic activity of PTSD subjects was more pronounced and long lasting in response to the combat film than to the noncombat film, but type of film had no systematic effect on control subjects' responses. These findings are consistent with biological models that posit sympathoadrenal activation in response to memory-evoking cues of traumatic events in PTSD.
Adult↗
Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity.
To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis.
Adult↗
The thermic effect of feeding in older men: the importance of the sympathetic nervous system.
We have previously published direct evidence that approximately one third of the thermic effect of feeding (TEF) in young healthy men can be accounted for by the meal-induced increment in sympathetic nervous system (SNS) activity. The elderly are known to have abnormal beta-adrenergic mechanisms and blunted responsiveness to sympathetic stimulation. Therefore, we postulated that the elderly might also have a blunted thermic response to a meal. In the present study, we evaluated the TEF in 25 young (age, 29.4 +/- 4.6 years) and 12 older (66.6 +/- 7.0 years), healthy weight-stable, untrained, nonsmoking men on no medications. Energy expenditure (ventilated hood system) and SNS activity (arterialized plasma catecholamine concentrations and norepinephrine [NE] kinetics) were measured before and following ingestion of an 800-kcal high-carbohydrate meal. At baseline, arterialized plasma NE concentration (P = .001) and appearance rate (P = .05) were 40% and 28% higher, respectively, in the elderly. Resting energy expenditure was related to fat-free mass (r = .54, P less than .01), and was 21% lower in the older men (P less than .01). Energy expenditure increased in both groups following the meal, but this TEF was 48% lower in the older men (P less than .001). This reduced TEF observed in the older subjects was associated with only a slight, nonsignificant, blunting of the SNS response to the meal. The TEF was related to the arterialized plasma NE appearance rate in the young, but not the older group. The TEF was unrelated to either glucose or insulin concentrations in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pancreatic and extrapancreatic galanin release during sympathetic neural activation.
To address the hypothesis that the neutropeptide, galanin, functions as a sympathetic neurotransmitter in the endocrine pancreas, we sought to determine if galanin is released from pancreatic sympathetic nerves during their direct electrical stimulation in halothane-anesthetized dogs. During bilateral thoracic splanchnic nerve stimulation (BTSNS), both peripheral arterial and pancreatic venous levels of galanin-like immunoreactivity (GLIR) increased (delta at 10 min = +92 +/- 31 and +88 +/- 25 fmol/ml, respectively). Systemic infusions of synthetic galanin demonstrated that 1) the increment of arterial GLIR observed during BTSNS was sufficient to modestly restrain basal insulin secretion and 2) only 25% of any given increment of arterial GLIR appears in the pancreatic vein, suggesting that the pancreas extracts galanin, as it does other neurotransmitters. By use of 75% for pancreatic extraction of circulating galanin, it was calculated that pancreatic galanin spillover (output) increased by 410 +/- 110 fmol/min during BTSNS. To reinforce the conclusion that pancreatic sympathetic nerves release galanin, GLIR spillover was next measured during direct local stimulation of the pancreatic sympathetic input produced by electrical stimulation of the mixed autonomic pancreatic nerves (MPNS) in the presence of the ganglionic blocker, hexamethonium. During this local pancreatic sympathetic nerve stimulation, arterial GLIR remained unchanged, but pancreatic venous GLIR increased by 123 +/- 34 fmol/ml. Thus pancreatic GLIR spillover increased by 420 +/- 110 fmol/min during MPNS in the presence of hexamethonium. We conclude that galanin is released from both pancreatic and extrapancreatic sources during sympathetic neural activation in dogs.
Animals↗
Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging.
To assess the effect of exercise training on the insulin resistance and impaired pancreatic B-cell function of aging, we studied 13 healthy older men (ages 61-82 yr) before and after 6 mo intensive endurance exercise. An index of insulin sensitivity (SI) was measured using Bergman's minimal model. Intravenous glucose tolerance was quantified using the glucose disappearance constant (KGlc) while oral glucose tolerance was assessed after a 100-g glucose load. B-cell function was evaluated by measuring the acute insulin response (AIR) to glucose injection at fasting glucose (AIRGlc) and the AIR to arginine at multiple clamped glucose levels. Exercise produced an endurance training effect as demonstrated by an 18% increase in maximum O2 consumption (VO2max) [38.2 +/- 1.4 to 45.0 +/- 1.1 (SE) ml.kg fat-free mass-1.min-1, P less than 0.001]. An unchanged fasting glucose (5.3 +/- 0.2 to 5.4 +/- 0.2 mM) despite a reduced fasting insulin (61 +/- 6 to 48 +/- 6 pM, P less than 0.01) suggested exercise training improved insulin sensitivity. This was confirmed by a 36% increase in SI from 3.47 +/- 0.41 to 4.71 +/- 0.42 x 10(-5) min-1/pM (P = 0.01). Intravenous glucose tolerance did not change as measured by KGlc, which was 1.46 +/- 0.09 before and 1.48 +/- 0.16%/min after exercise training. Likewise, the incremental glucose response to oral glucose (633 +/- 49-618 +/- 45 mM.min) was unchanged. B-cell function was decreased as reflected by AIRGlc (351 +/- 73-245 +/- 53 pM, P less than 0.01) and the AIRArg at maximal glycemic potentiation (AIRmax, 1,718 +/- 260-1,228 +/- 191 pM, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Differential effects of aging on neuroendocrine responses to physostigmine in normal men.
We assessed the effects of age on cholinergic regulation of the hypothalamic-pituitary-adrenal axis and other neuroendocrine systems by measuring the plasma cortisol and beta-endorphin responses to an infusion of the centrally active cholinesterase inhibitor physostigmine (0.0125 mg/kg) in 12 healthy older men (68 +/- 1.7 yr) and 9 healthy young men (25 +/- 1.4 yr). We also measured the responses to physostigmine of plasma GH, arginine vasopressin, epinephrine, and norepinephrine (NE). As estimated by comparing calculated areas under the curve, older subjects had greater cortisol (P = 0.02) and beta-endorphin (P less than 0.01) secretory responses, but a reduced GH (P less than 0.01) secretory response. The arginine vasopressin response did not differ between groups. By analysis of variance, older subjects also had a greater epinephrine response (P = 0.01). Older subjects had higher basal NE concentrations (P less than 0.05), but NE responses to physostigmine did not differ between groups. These findings suggest age-related enhancement of the cholinergic stimulatory regulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla. They also confirm previous reports of reduced GH secretory response with aging in normal men.
Adult↗
Desipramine potentiates anesthetic and lethal effects of ketamine.
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Animals↗
The effect of diet or exercise on plasma norepinephrine kinetics in moderately obese young men.
An increase in sympathetic nervous system (SNS) activity in the obese has been described by some but not all investigators. It is possible that an increase in SNS tone may play a role in the predisposition to atherosclerotic cardiovascular disease noted in the obese. The effect of dietary weight loss or exercise training on resting SNS activity in moderately obese subjects has not been extensively studied and the results of previous studies are conflicting. Therefore, we prospectively evaluated resting SNS activity in healthy moderately obese subjects randomized to either a three month dietary weight loss (n = 13) or endurance exercise training (n = 18). All subjects were weight stabilized on a constant composition diet for 10 days prior to study both before and after the interventions. Although both groups lost weight, weight loss was greater in the diet group (-13.6 +/- 6.7 vs -2.3 +/- 3.4 kg, P less than 0.001). The composition of weight loss was also different with 32 percent of total weight loss as fat free mass (FFM) in the dieters compared to no significant change in FFM in the exercisers. The caloric requirement for weight stabilization declined after the diet but increased following exercise training (-247 vs + 202 kcal/day, P less than 0.001). No significant changes in blood pressure occurred in either group, and neither group had a significant change in resting plasma norepinephrine concentration. Plasma epinephrine concentrations were also unchanged. However, SNS activity as reflected by arterialized plasma NE kinetics revealed that NE appearance rate declined by 17 percent after dietary weight loss (P less than 0.01), but was not significantly changed after exercise training. These results suggest that dietary weight loss is more effective than exercise training in reducing overall resting SNS activity in normotensive subjects. Since exercise training is known to reduce the SNS response to a given submaximal workload, a combination of diet plus exercise might be the most effective way to reduce overall SNS activity and its possible role in the premature atherosclerosis associated with obesity.
Adolescent↗
Neuroendocrine responses to physostigmine in Alzheimer's disease.
To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, beta-endorphin, and epinephrine responses to a cholinergic challenge elicited by intravenous administration of the acetylcholinesterase inhibitor physostigmine (0.0125 mg/kg) in male patients with AD (n = 12) and compared their responses with those of age-matched normal control subjects (n = 12). Physostigmine promptly increased plasma arginine vasopressin (tenfold), beta-endorphin (twofold to threefold) and epinephrine (threefold) levels in elderly control subjects. In contrast, patients with AD showed attenuated responses to physostigmine. When controls and patients with AD who experienced nausea (n = 2 and n = 6, respectively) were excluded, the arginine vasopressin, beta-endorphin, and epinephrine responses of patients with AD were significantly less than those of control subjects. These data suggest that the central nervous system cholinergic deterioration of AD results in decreased responsiveness of neuroendocrine systems that are regulated by central cholinergic mechanisms.
Aged↗
Pressor, norepinephrine, and pituitary responses to two TRH doses in Alzheimer's disease and normal older men.
Changes in blood pressure (BP), plasma norepinephrine (NE), serum prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) associated with infusions of two thyrotropin-releasing hormone (TRH) doses (0.1 mg, 0.5 mg) were examined in 10 men with early-onset Alzheimer's disease (AD) and nine normal matched controls. During the first 5 min after TRH infusion, significant increases from baseline in systolic BP (p less than 0.001), diastolic BP (p less than 0.001), and plasma NE (p less than 0.006) occurred in the study subjects. The magnitude of the BP and NE responses did not differ significantly as a function of TRH dose (p greater than 0.3). Diastolic pressor responses to TRH were substantially blunted in AD subjects relative to controls, after both the 0.1-mg (p less than 0.003) and 0.5-mg (p less than 0.02) doses. There were trends toward attenuated responses in the AD subjects for systolic BP (p less than 0.09) and plasma NE (p less than 0.07). Significant increments in serum PRL, LH, and FSH (all p less than 0.001) also occurred after TRH, but the magnitude of the hormone responses did not differ significantly between the AD and the normal subjects (p greater than 0.18). These results suggest the possibility that TRH-evoked activation of the sympathetic nervous system (SNS), as reflected by pressor and plasma NE responses, may be attenuated in men with early-onset AD.
Aged↗
Impaired sympathetic nervous system response to cognitive effort in early Alzheimer's disease.
Sympathetic nervous system responses to a cognitive challenge and a physiologic stimulus (upright posture) were compared in 10 patients with early Alzheimer's Disease and a group of healthy older adults. Plasma catecholamine and cardiovascular responses to upright posture were similar in the two groups. However, sympathetic activation during mental effort was impaired in the patient group; this difference did not appear to be attributable to motivational factors. Alzheimer's Disease is associated with a defect in sympathetic nervous system function that is specifically linked to cognitive effort and appears early in the course of the disease.
Aged↗