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Biomedical subjects

C R Lake

Publications and source records attributed to C R Lake.

At least 91 records · Page 5Linked to original sources
PubMed1983

Sympathetic nervous system function in XYY subjects.

Initial reports of males with the XYY sex chromosome anomaly indicated that these individuals excessively exhibit impulsive, aggressive, and criminal behavior. Central nervous system (CNS) defects, including low intelligence, in certain XYY subjects may be associated with these antisocial behaviors. The sympathetic nervous system (SNS) is activated in stressful conditions of "fight or flight" upon standing up from a supine posture, with physical exercise, and with aggressive behavior. Norepinephrine (NE) is the principal neurotransmitter of the SNS, and plasma levels of NE and dopamine-beta-hydroxylase are indices of SNS function. We questioned the integrity of SNS function in XYY subjects for two reasons: (1) their inferred propensity for aggressive behavior and the association of this behavior with increased NE levels; and (2) their potential for CNS dysfunction, which could be reflected in abnormal SNS regulation by the CNS. In the current study plasma levels of NE in XYY subjects are nonsignificantly higher than in normal volunteers. Additionally, XYY patients have a normal NE half-life indicating normal SNS activity and metabolism. Thus, we are unable to document with confidence any abnormality in SNS function in these XYY subjects.

Adolescent↗
PubMed1983

Effect of long-term clorgyline administration on human platelet alpha-adrenergic receptor binding and platelet cyclic AMP responses.

Platelet alpha 2-adrenergic receptor number and physiologic responsiveness, as well as plasma norepinephrine (NE), were evaluated in psychiatric patients with major depressive disorder before and during chronic clorgyline treatment. The alpha 2-adrenergic receptor number was determined by measuring the binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes. Physiologic responsiveness was determined by measuring the response of cyclic adenosine 3'-5'-monophosphate (cAMP) to prostaglandin E1 (PGE1), and the inhibition of the PGE1-stimulated cAMP response by NE in intact platelets. No significant differences from pretreatment values were observed in platelet alpha 2-adrenergic binding or responsiveness during clorgyline treatment. Baseline platelet cAMP production and plasma NE levels were significantly decreased after chronic clorgyline treatment. Previous studies on animals and humans have suggested that brain alpha 2-adrenergic receptor responsiveness decreases during chronic clorgyline treatment. The present findings therefore suggest that such changes may represent adaptations induced by long-term clorgyline administration which may differ between the brain and the platelet, thus illustrating potential limitations of the study of platelet alpha 2-adrenergic receptors as a model for central alpha 2-adrenergic receptor adaptation.

Adult↗
PubMed1983

Clinical studies of monoamine receptors in the affective disorders and receptor changes with antidepressant treatment.

Pre-clinical and clinical studies suggest that the responsiveness of monoamine and cholinergic receptors may be altered in the affective disorders and that antidepressants may modify the sensitivity of these receptors. The growth hormone response to clonidine is reduced in depressed patients compared to controls according to several independent studies, suggesting that post-synaptic alpha 2-adrenergic receptors may be less responsive in depressed patients. The cortisol response to clonidine is enhanced in depressed patients compared to controls in our study raising the possibility that cortisol hypersecretion in depressed patients may be related to noradrenergic dysfunction. The hypotensive response to clonidine is blunted in patients on chronic antidepressant treatment with either clorgyline or desipramine suggesting that pre-synaptic alpha 2-adrenergic receptors may subsensitize with chronic antidepressant treatment. The prolactin increase in response to fenfluramine is less in depressed patients compared to controls suggesting decreased functional activity of the serotonergic system in depression. Platelet alpha 2-adrenergic receptor number as measured by tritiated dihydroergocriptine (3H-DHE) binding is increased in depressed patients compared to controls, while cyclic 3'-5' adenosine monophosphate (cAMP) production in response to prostaglandin E1 (PGE1) and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production are reduced in the platelets of depressed patients. Thus, it is not clear that increased 3H-DHE binding reflects increased functional responsiveness and might in fact be compensatory to decreases in functional responses of alpha 2-adrenergic receptors.

Clonidine↗
PubMed1983

Sympathetic nervous system "switch off" with severe hypothermia.

Hypothermia occurs frequently in the critically ill patient, yet little is known about the endogenous catecholamine response to this stress. To study this problem, we measured heart rate (HR), mean arterial blood pressure (MAP), and plasma levels of norepinephrine (NE) and epinephrine (Epi) in subhuman primates (baboons) during progressive hypothermia from 37 degrees to 29 degrees C and then during rewarming to 37 degrees C. As the core temperature decreased from 37 degrees to 33 degrees C, HR and MAP increased significantly (p less than 0.05), but as core temperature further decreased from 33 degrees to 29 degrees C, the HR and MAP fell to prehypothermic levels. Plasma concentrations of NE and Epi increased significantly (p less than 0.01) as core temperature fell from 37 degrees to 31 degrees C, but as core temperature dropped from 31 degrees to 29 degrees C, plasma NE and Epi levels decreased towards prehypothermic concentrations. These findings indicate that the sympathetic nervous system (SNS) responds quickly to hypothermia but may be "switched off" at a threshold temperature of about 29 degrees C. We speculate that hypotensive patients with temperatures less than or equal to 29 degrees C may benefit from infusions of exogenous catecholamines, especially if there have been only minimal benefits achieved with conventional therapy such as fluids, and an increase in ambient temperature.

Animals↗
PubMed1983

Growth hormone response to clonidine in obsessive-compulsive patients.

We have observed a lesser growth hormone response to intravenous clonidine administration in nine obsessive-compulsive disorder patients meeting research diagnostic criteria than in nine matched controls. The obsessive-compulsive disorder patients had higher plasma free 3-methoxy-4-hydroxyphenylglycol and plasma norepinephrine levels before clonidine than the controls. As blunted growth hormone responses to clonidine are also characteristic of affective disorder patients, these results support other observations of a psychobiologic affinity between these two groups and are also compatible with an association between increased presynaptic noradrenergic activity and decreased post-synaptic receptor responsiveness.

Adolescent↗
PubMed1983

Fenfluramine lowers plasma norepinephrine in overweight subjects.

The effect of fenfluramine on sympathetic nervous system activity was determined in 12 normotensive, obese men. Supine plasma norepinephrine (NE) concentrations decreased (p less than 0.001) from pretherapy levels (298 +/- 39 pg/ml) after one (166 +/- 30 pg/ml) and four weeks (171 +/- 28 pg/ml) of fenfluramine (60 mg daily). Fenfluramine did not alter the sympathetic nervous system responses to orthostasis or exercise. Fenfluramine-induced decreases in heart rate (72 +/- 3 to 67 +/- 4 beats/min, p less than 0.01) and mean arterial blood pressure (90 +/- 2 to 81 +/- 2 mmHg; p less than 0.005) were observed after only one week of therapy despite no significant change in body weight. We conclude that fenfluramine may be a useful agent in the treatment of patients with sympathetic hyperactivity. The effects of fenfluramine on given subsets of patients and control subjects are also defined.

Adult↗
PubMed1983

Effect of clonidine on sympathetic nervous system activity in patients with essential hypertension.

This study analysed the effects of both seven and 30 days of treatment with clonidine on heart rate, blood pressure (BP), plasma norepinephrine (NE) levels and dopamine-beta-hydroxylase (DBH) activity at rest and after standing in seven patients with essential hypertension. The patients and 10 age-matched normotensive control subjects were evaluated under medication-free baseline conditions; the hypertensive patients were then given clonidine 0.1 mg twice daily. Baseline plasma NE and DBH levels were similar between the groups. Seven and 30 days of clonidine therapy reduced blood pressure (p less than 0.001) and NE concentrations (p less than 0.05) significantly. Clonidine did not effect the percent increase in NE induced by standing and was not associated with orthostatic hypotension. The blood pressure lowering effects of clonidine appear related to the centrally mediated and/or direct suppression of peripheral noradrenergic activity, indicating the utility of clonidine in cases of hypertension were the sympathetic nervous system (SNS) is hyperactive. Clonidine may also prove especially useful in cases where the initial pharmacotherapy (such as a diuretic) causes activation of the SNS.

Adult↗
PubMed1983

Development of a primate model of exposure hypothermia.

A nonhuman primate model of exposure-induced hypothermia was developed and the hemodynamic effects of hypothermia were evaluated in five animals. With decreasing core temperature from 37 degrees C to 33 degrees C there was a 47% increase in heart rate, a 23% increase in mean arterial pressure, a 48% increase in cardiac output, a 260% increase in oxygen consumption, and a 237% increase in minute ventilation. As the core temperature decreased from 33 degrees C to 29 degrees C there were decreases in the heart rate, blood pressure, and cardiac output such that at 29 degrees C these values were not significantly different from the values obtained at 37 degrees C. However, the oxygen consumption was still 180% increased and the minute ventilation 40% higher at 29 degrees C than at 37 degrees C. This model will allow the evaluation of the physiology of hypothermia and the effectiveness of different rewarming techniques.

Animals↗
PubMed1982

Plasma norepinephrine and dopamine-beta-hydroxylase activity in schizophrenia.

Plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity may be altered by changes in posture, pulse rate, and BP. Twenty-three drug-free schizophrenic, ten schizoaffective, and 24 normal control subjects, and a separate group of eight schizophrenic patients treated with chlorpromazine hydrochloride and haloperidol comprised the sample. Drug-free schizophrenic patients showed higher plasma NE levels while standing and higher pulse rates when supine and standing than normal subjects. Following chlorpromazine therapy, but not following haloperidol treatment, plasma NE level increased with patients supine and standing, pulse rate increased with patients standing, and systolic BP decreased with patients standing. These findings suggest (1) a decreased peripheral alpha-adrenergic postsynaptic receptor sensitivity in schizophrenia and (2) a peripheral alpha-adrenergic blocking mechanism in chlorpromazine-induced hypotension.

Adult↗
PubMed1982

Plasma, urine, and CSF catecholamine concentrations during and after ketamine anesthesia.

Ketamine has been reported to increase plasma catecholamine concentrations. Prior investigations have only studied plasma catecholamine levels for short periods after iv ketamine. Because ketamine is one of the most frequently used anesthetic agents in critical care research, we evaluated ketamine's effect on catecholamines over a longer period of time. Plasma, urine, and CSF epinephrine (E) and norepinephrine (NE) concentrations were serially measured during a 2-h ketamine infusion and a subsequent 2-h "wake-up" period. No changes in heart rate, mean arterial blood pressure or urine, plasma, and CSF NE concentrations were noted during the 4-h study period, whereas there were significant (p less than 0.005) increases in urine, plasma, and CSF E levels during ketamine infusion but not during the wake-up period. An unexpected finding was that the baboons have very high basal plasma E levels versus those in humans. It is concluded that ketamine is a useful anesthetic agent for critical care research involving measurements of sympathetic nervous system activity. The interesting observation of high plasma levels in the baboon warrants further investigation.

Anesthesia↗