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Biomedical subjects

C R Lake

Publications and source records attributed to C R Lake.

At least 73 records · Page 4Linked to original sources
PubMed1984

Sympathetic nervous system sensitivity to hemorrhagic hypotension in the subhuman primate.

The endogenous catecholamine response to hemorrhagic hypotension is poorly defined since most data have been derived from experiments in lower animal species. To clarify this situation we studied the plasma norepinephrine (NE) and epinephrine (Epi) responses to hemorrhagic hypotension in ten healthy male baboons (Papio anubis). After an overnight fast, animals were tranquilized with 100 mg of ketamine hydrochloride after which femoral artery and vein catheters were inserted. The animals then underwent phlebotomy of 20 ml/kg over 60 minutes with retransfusion of the autologous blood over the next 30 minutes. Plasma specimens for catecholamines were collected at 5, 15, 30, and 60 minutes during phlebotomy and again at 15 and 30 minutes during retransfusion. Plasma NE and Epi concentrations were measured by a radioenzymatic technique. Mean arterial blood pressure (MAP) decreased (p less than 0.01) and heart rate (HR) increased (p less than 0.01) within 15 minutes of phlebotomy, and these variables returned to baseline with retransfusion. Plasma NE and Epi levels increased (p less than 0.025) within 5 minutes of the onset of 'hemorrhage' and within 15 minutes plasma NE concentrations were 56% above baseline, whereas plasma Epi levels were six times greater than baseline. With retransfusion, plasma NE and Epi levels returned to baseline concentrations. We conclude: 1) in a primate species, the sympathetic nervous system responds rapidly to hemorrhage; 2) contrary to prior studies in rats, plasma NE increases as rapidly as Epi but not to the same degree; 3) plasma NE and Epi concentrations rapidly return to baseline levels with fluid resuscitation; and 4) there is little justification for the use of exogenous synthetic catecholamines in hemorrhagic hypotension where fluid resuscitation remains the treatment of choice.

Animals↗
PubMed1984

Differential inhibitory noradrenergic responses to clonidine in 25 depressed patients and 25 normal control subjects.

The authors measured plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine, blood pressure, and heart rate responses to the alpha 2-adrenergic agonist clonidine in 25 depressed patients and 25 normal control subjects. In the control subjects clonidine reduced plasma norepinephrine, blood pressure, and heart rate significantly more than placebo. In the depressed patients clonidine reduced blood pressure and the percent fall in plasma norepinephrine but not plasma MHPG or heart rate significantly more than placebo. The absolute and percent reductions in plasma MHPG and heart rate following clonidine were significantly less than in control subjects. These results raise the possibility that the sensitivity of the alpha 2-adrenergic receptors inhibitory to noradrenergic output may be reduced in depression.

Adult↗
PubMed1984

Alpha-adrenergic receptors in orthostatic hypotension syndromes.

Alpha-adrenergic receptor function was measured in platelets from patients with orthostatic hypotension and normotensive controls. Patients with idiopathic orthostatic hypotension (IOH) or multiple system atrophy (MSA) had more alpha-receptors than controls. Patients with IOH, but not MSA, produced less prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) than controls. Patients with sympathotonic orthostatic hypotension (SOH) were similar to controls in receptor number and cAMP production. The percent norepinephrine (NE) inhibition of PGE1-stimulated cAMP production was similar in patients and controls. An increase in alpha-receptor number may result from decreased peripheral NE secretion in IOH and MSA. Increased alpha-receptor number and decreased cAMP production, which accompany essential hypertension, may contribute to the supine hypertension of IOH, and an increase in alpha-receptor number may contribute to the supine hypertension of MSA. SOH patients appear to have no abnormalities of alpha-receptor function.

Adolescent↗
PubMed1984

Effect of ionizing radiation on physiological function in the anesthetized rat.

Exposure of pentobarbital-anesthetized rats to 14.5-MeV electrons results in radiation-induced physiological dysfunction. Responses include transient hypotension, a transient decrease in heart rate, respiratory dysrhythmias, and a prolonged increase in pulse pressure. Magnitudes of these responses are dose related, and maximal responses can be elicited by either whole- or partial-body (head or abdominal) exposure to 10,000 rad. These responses were associated with a fivefold increase in arterial plasma concentration of epinephrine, whereas histamine, norepinephrine, and beta-endorphin did not change during the first minute after the onset of exposure. Administration of diphenhydramine, a histamine receptor antagonist, resulted in a significant decline of baseline cardiovascular function and inhibited radiation-induced cardiovascular dysfunction. The diphenhydramine-induced decrease in preexposure blood pressure was reversed by angiotensin infusion, but this procedure failed to restore the mechanism(s) responsible for the cardiovascular responses to radiation. Results of these experiments and information available in the literature support the hypothesis that these responses are due to an interference in the autonomic pathways that modulate cardiovascular function.

Anesthesia↗
PubMed1984

CNS stimulants and the look-alike drugs.

Abuse of amphetamine and especially the stimulant look-alikes represent a serious problem in the United States. The danger of amphetamine lies in its ability to produce tolerance, psychological addiction, psychosis, hypertensive crisis, and major depression following withdrawal after long-term use. The danger of the look-alikes is of a psychosocial nature and has less to do with the physical properties of the drugs. Easy availability and a casual attitude toward these drugs may introduce children and young adults to the concept of recreational use of drugs at an early age. Look-alikes also divert the efforts of law enforcement officials whose time is better spent on efforts to control illegal distribution of controlled substances. However, look-alikes do produce severe to life-threatening effects including seizures, hypertensive crises, and psychoses. Unfortunately, there are no fast and easy solutions to the stimulant drug abuse problem. Abuse of CNS stimulants has a long history. Effective approaches must involve greater education about the dangers of these drugs and improved recognition among medical professionals of trends in CNS stimulant abuse in order to better diagnose and treat resulting problems. It is unlikely that federal controls on amphetamine production can be increased. The OTC drugs, such as PPA, caffeine, and ephedrine could be moved to prescription-only status to emphasize their potential for abuse and for producing adverse reactions, but this approach is counter to society's current trend toward self-medication.

Amphetamine↗
PubMed1984

Psychopharmacology in the intensive care unit.

The task of the psychopharmacologist in the ICU does not stop with a recommendation of the best drug and dosage. The clinical course of patients in ICUs is often stormy. With each change, the appropriateness of the chosen psychopharmacologic treatment may be questioned. Is the patient experiencing a side effect? Should the drug be discontinued or the dosage altered? Nonpsychiatrists are often unfamiliar and uncomfortable with psychotropic medications and are not as likely to accurately assess side effects or therapeutic progress. Try to anticipate the more likely complications in the progress notes without being too lengthy, and attempt to verbally communicate impressions and recommendations. Finally, stay abreast of the patient's progress, and make it clear that you are available for consultation and advice. In this way you may assure that the patient will be best able to tolerate and benefit from ICU treatment.

Antidepressive Agents↗
PubMed1984

Autonomic degeneration and altered blood pressure control in humans.

The study of patients with partial or total defects of their sympathetic nerves can help clarify the role of the sympathetic nervous system in blood pressure control. Denervation supersensitivity of both beta and alpha receptors develops in humans and is proportional to the degree of sympathetic withdrawal. Although alterations in beta-receptor sensitivity are familiar responses to beta agonists or antagonists, patients with decreased norepinephrine (NE) levels appear to develop alpha-receptor supersensitivity of greater hemodynamic importance. When beta supersensitivity is marked, there may be a pressor response to beta blockade even when circulating levels of NE and epinephrine are very low. Indomethacin blocks prostaglandin synthesis and causes an increase in blood pressure in patients with partial autonomic neuropathies. The drug increases blood pressure by enhancing alpha- and diminishing beta-receptor sensitivity to NE, so it is effective only in patients who have some residual NE release.

Autonomic Nervous System Diseases↗
PubMed1984

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

The sympathetic nervous system (SNS) plays a major role in blood pressure regulation. Although the exact relationship of the SNS to the etiology of hypertension remains undetermined, many of the agents used to treat hypertension interfere with this system. Clonidine, methyldopa, guanethidine, and reserpine decrease SNS tone whereas hydralazine, minoxidil, and hydrochlorothiazide increase it. Most evidence suggests that beta-adrenergic blocking agents decrease SNS activity. The effect of prazosin and captopril on the SNS requires further study. The appropriate use of these antihypertensive agents requires a knowledge of their sites of action and the physiological reflexes they induce. Efficacy, toxicity, and effective drug combinations can be predicted based on their mechanism of action and effect on SNS activity.

Antihypertensive Agents↗
PubMed1984

Psychopharmacology. An historical perspective.

This article explores the field of psychopharmacology from an historical perspective. Part 1 traces the uses throughout history of psychoactive substances that are widely abused by modern society. Part 2 examines the development in the 1950s and 1960s of drugs and other physical methods that have revolutionized the treatment of the mentally ill.

Basidiomycota↗
PubMed1984

Diagnostic dosages of protirelin (TRH) elevate BP by noncatecholamine mechanisms.

While performing thyroid function tests, we noticed that protirelin (TRH) raised BP, and, therefore, we investigated the effect of diagnostic dosages of protirelin (500 micrograms) on plasma catecholamine levels and cardiovascular function in eight patients one day before, one day after, and four weeks following heart surgery. Mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine (NE), epinephrine (EPI), dopamine (DA), thyroid hormone (triiodothyronine [T3], thyroxine), and thyrotropin (TSH) levels were measured before and after the intravenous injection of protirelin. Protirelin increased MAP transiently from 88 +/- 2 to 103 +/- 3 mm Hg (before surgery), 86 +/- 4 to 102 +/- 4 mm Hg (one day after surgery), and 86 +/- 4 to 104 +/- 5 mm Hg (four weeks after surgery). There were no notable changes in HR or plasma NE, EPI, or DA levels. The T3 and TSH response to protirelin was normal on all three study days. Protirelin raised MAP by an effect on systemic vascular resistance (SVR) rather than an increase in cardiac output. We conclude the following: (1) diagnostic dosages of protirelin transiently elevate MAP and SVR by a noncatecholamine mechanism, (2) clinicians who perform protirelin tests should be aware of protirelin's transient pressor effects.

Adult↗
PubMed1984

Epinephrine absorption after intratracheal administration.

Tracheal intubation during cardiopulmonary resuscitation often precedes establishment of an intravenous route for the administration of drugs. To determine the efficacy of intratracheal administration of drugs during cardiopulmonary resuscitation we measured plasma catecholamine levels and hemodynamic responses to intratracheal epinephrine (EPI) administration using a double-blind, randomized crossover design in 7 male baboons (Papio anubis), each studied twice, who received 5 ml of 1:10000 EPI on one day and 5 ml of 0.9% NaCl on another day. Arterial blood samples for measurement of plasma EPI and norepinephrine (NE) concentrations were collected, and heart rate (HR) and mean arterial blood pressure (MAP) were measured before and 1, 2, 4, 8, 16, and 30 min after intratracheal drug administration. Intratracheal EPI significantly (P less than 0.05) elevated HR to 120 +/- 6 from 105 +/- 6 beats/min, MAP to 120 +/- 4 from 112 +/- 5 mm Hg, and plasma EPI to 8882 +/- 2143 from 928 +/- 209 pg/ml within 1 min of administration, and these effects persisted for 30 min. Plasma NE levels did not change after intratracheal EPI administration. None of the four variables changed after intratracheal saline was given. We conclude that in subhuman primates, intratracheal EPI is rapidly absorbed and is an effective pressor agent when given by this route; and that these data lend support to the clinical practice of intratracheal EPI administration during cardiac arrest or in the treatment of shock.

Absorption↗
PubMed1984

The acute psychiatric diagnostic interview.

The general outline of a psychiatric diagnostic interview given in Table 1 includes some broad suggestions for the amount of time to spend on each section. As a structured interview based on a symptom checklist questionnaire yields higher frequency of reports of symptoms, it is advisable to follow this type of format rather than a totally unstructured interview technique. Sim recommends a structured format that lends itself to computerization. Griest and colleagues suggest a computer interview, and there are data supporting the diagnostic accuracy of such a system. Within the framework of any diagnostic interview, a thorough exploration of the 10 critical elements listed in Table 5 is essential for accurate diagnosis. This information, which is usually obtainable in about 30 minutes, will enable the clinician to make a preliminary diagnosis, decide upon pharmacotherapy, and determine if hospitalization is warranted. A more intensive but lengthy and time-consuming structured diagnostic interview is the Schedule for Affective Disorders (SADS), which is more appropriate for inpatients or patients being considered for a research protocol.

Acute Disease↗
PubMed1984

Plasma catecholamine levels in normal subjects and in patients with secondary hypertension.

We compared normal values for human venous norepinephrine (NE) and epinephrine (E) as reported in the literature with values determined in this laboratory and we measured and contrasted NE levels in patients with primary and secondary hypertension. Analysis of published data from many laboratories involving more than 800 supine, resting, healthy subjects indicated an average circulating level of venous NE of 260 pg/ml and of E, about 35 pg/ml. Supine levels of NE normally double when normal subjects stand for 5 min. This simple test provides one assessment of overall sympathetic nervous system integrity. Levels of catecholamines have been extensively studied in essential hypertension but much less so in secondary hypertension. Of the groups we studied with secondary hypertension (diabetes mellitus, primary hyperaldosteronism, polycystic kidney disease, chronic bilateral renal parenchymal disease, and unilateral renal arterial stenosis), only the group with renal parenchymal disease had supine NE levels significantly higher than the control group. Patients with essential hypertension and diabetes had a blunted increase in NE on standing. Plasma levels of NE do not reliably differentiate these groups of secondary hypertension from one another or from patients with primary hypertension.

Adolescent↗
PubMed1984

Plasma norepinephrine and epinephrine levels in essential hypertension.

Almost all comparative studies of plasma catecholamines in patients with essential hypertension (EH) and in normotensive controls have reported higher mean norepinephrine (NE) or epinephrine (E) levels in the hypertensive patients, but only about 40% of the studies have been positive, i.e., have reported statistically significant hypertensive-normotensive (H-N) differences. Virtually all studies of NE in young, consistently hypertensive patients were positive, as well as all studies of E in relatively tachycardic patients. Plasma NE increased with age in normotensive control but not EH groups. The likelihood that a study was positive with respect to NE was independent of the likelihood with respect to E. In 189 individuals with EH and 130 normotensive controls, NE increased with age in controls but not in patients with EH, so that the extent of the H-N difference in NE varied inversely with patient age. Among 41 other individuals with EH and 59 other normotensive controls, the distributions of NE and E values were shifted upward in EH. NE and E values were uncorrelated. Plasma NE levels are abnormally high in some patients with EH--especially those who are young and consistently hypertensive--and E levels are independent of age and NE. Increased sympathetic nervous system and/or sympathoadrenomedullary activity characterize a proportion of patients with EH.

Adolescent↗
PubMed1983

Local dental anesthesia with epinephrine. Minimal effects on the sympathetic nervous system or on hemodynamic variables.

To define the hemodynamic effects of local dental anesthesia, we measured the mean arterial pressure (MAP), heart rate, and plasma catecholamine responses for 60 minutes following an inferior alveolar nerve block with epinephrine-and nonepinephrine-containing lidocaine hydrochloride anesthesia in 14 men using a randomized double-blind crossover trial. Lidocaine alone caused no significant change in MAP or heart rate and only slight, transient changes in plasma catecholamine concentrations when compared with baseline values. Lidocaine with epinephrine caused significant, sustained (60 minutes) increases in plasma epinephrine concentrations (mean +/- SEM, 27 +/- 4 to 94 +/- 13 pg/mL) and a slight, but transient (two-minute) increase in heart rate from 68 +/- 3 to 70 +/- 3 beats per minute. Lidocaine with epinephrine caused no significant change in MAP. There is no significant hemodynamic response to lidocaine dental anesthesia (with or without epinephrine) in healthy young men.

Anesthesia, Dental↗