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Biomedical subjects

J M Cottet-Emard

Publications and source records attributed to J M Cottet-Emard.

At least 73 records · Page 4Linked to original sources

Response of noradrenaline and dopamine to hypoxia and sympathectomy: evidence for an independent dopaminergic reactivity.

In order to assess the status of dopamine in the periphery, we submitted rats to sympathectomy (with guanethidine), to hypoxia, and to both, and measured the concentration and turnover of noradrenaline and dopamine in peripheral organs. Sympathectomy decreased noradrenaline content by 96-99% in all the organs tested. In contrast, dopamine content, which was decreased by 90% in the heart, was not significantly changed in the bladder or lungs. Based on dopamine decrease after guanethidine, and on dopamine:noradrenaline ratios in organs, we conclude that in the heart the dopamine is contained mostly in noradrenergic terminals. In other organs it appears to be contained in non-noradrenergic structures. These are found in: the bladder, stomach, lungs, and kidneys, in decreasing importance. We estimated the turnover of noradrenaline by measuring the decrease of its concentration after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine. Among the five organs studied, the turnover of noradrenaline was increased by long-term hypoxia (10% O2, 15 days) in the heart only (+140%). An increase of sympathetic activity during hypoxia was also found in the kidneys and lungs as shown by the increase in turnover of dopamine that was suppressed by sympathectomy. Hypoxia induced large increases in dopamine concentration in the stomach and the lungs (70 and 190% respectively). These increases were not abolished by sympathectomy and we propose that they are related to a chemosensory function of dopamine-containing paraganglia in the stomach and the lung.

Animals↗

Hemodynamic and hormonal effects of prolonged anti-G suit inflation in humans.

This study examined the hemodynamic consequences of prolonged lower body positive-pressure application and their relationship to changes in the plasma concentration of the major vasoactive hormones. Six men [36 +/- 2 (SE) yr] underwent 30 min of sitting and then 3 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 2 h of tilt. In a similar noninflation experiment, the endocrine responses were measured in the suited subjects tilted for 3 h. Two-dimensional echocardiography was used to calculate ventricular volume and cardiac output. Measurements were made 30 min before and 30 and 90 min after inflation. Immediately after inflation, mean arterial pressure increased by 7 +/- 2 Torr and heart rate decreased by 16 +/- 4 beats/min. Left ventricular end-diastolic volume and systolic volume increased significantly (P less than 0.05) at 30 and 90 min of inflation. Cardiac output increased after 30 min of inflation and returned to the preinflation level at 90 min. Plasma norepinephrine and plasma renin activity were maximally suppressed after 15 and 90 min of inflation, respectively (P less than 0.05). No such hormonal changes occurred during control. Plasma sodium, potassium, and osmolality remained unchanged during both experiments. Thus, prolonged application of lower body positive pressure induces 1) a transient increase in cardiac output and 2) a marked and sustained decrease in plasma norepinephrine and plasma renin activity, which reflect an inflation-induced decrease in sympathetic activity.

Adult↗

Differential effects of long-term hypoxia on norepinephrine turnover in brain stem cell groups.

The influence of long-term hypoxia on noradrenergic cell groups in the brain stem was assessed by estimating the changes in norepinephrine (NE) turnover in A1, A2 (subdivided into anterior and posterior parts), A5, and A6 groups in rats exposed to hypoxia (10% O2-90% N2) for 14 days. The NE turnover was decreased in A5 and A6 groups but failed to change significantly in A1. The NE turnover was increased in the posterior part of A2 and remained unaltered in the anterior part. In normoxic rats, the hypotensive drug dihydralazine induced a reverse effect, namely increased NE turnover in anterior A2 and no change in posterior A2. The neurochemical responses to hypoxia were abolished by transection of carotid sinus nerves. The results show that long-term hypoxia exerts differential effects on the noradrenergic cell groups located in the brain stem. Peripheral chemosensory inputs control the hypoxia-induced noradrenergic alterations. The A2 cell group displays a functional subdivision: the posterior part is influenced by peripheral chemosensory inputs, whereas the anterior part may be concerned with barosensitivity.

Animals↗

Determination of free and conjugated normetanephrine and metanephrine in human plasma by high-performance liquid chromatography with electrochemical detection.

A simple method for the simultaneous assay of normetanephrine and metanephrine (both free and conjugated) in human plasma by high-performance liquid chromatography with electrochemical detection has been developed. The hydrolysed plasma is purified on a Dowex 50 H+ column, and the methoxylated amines are eluted with ammonia-methanol. The methoxyamines are assayed using a dual-series electrode arrangement with differential current measurement. This system greatly improves the assay specificity toward endogenous or exogenous metabolites and drugs. The high sensitivity of the method enables the determination in normal subjects of levels of normetanephrine and metanephrine.

Chromatography, High Pressure Liquid↗

Transection of carotid sinus nerve inhibits the turnover of dopamine and norepinephrine in long-term hypoxic carotid bodies: a biochemical and morphometric study.

To assess the efferent influence of the carotid sinus nerve on the catecholamine function and the vascularity in long-term hypoxic carotid bodies, rats were exposed to hypoxia (10% O2 in nitrogen for 1 and 3 weeks) after unilateral transection of the sinus nerve. In the intact carotid bodies, long-term hypoxia elicited several biochemical and morphological alterations: increased turnover of dopamine and norepinephrine, increased volume density of blood vessels, decreased volume density of glomic tissue. Transection of the sinus nerve reduced but did not abolish the increase in turnover of dopamine and norepinephrine evoked by hypoxia without preventing the structural alterations. Immunocytochemical studies revealed the presence of nerve fibres exhibiting neuropeptide Y-like immunoreactivity which persisted after the excision of the carotid sinus nerve. Nerve fibres showing substance P-like immunoreactivity were found in the intact carotid bodies but not in the carotid bodies deprived of sinus nerve. It is concluded that the sinus nerve exerts a stimulatory efferent control on the synthesis and release of dopamine and norepinephrine in rat carotid body during long-term hypoxia, but no appreciable vasodilatory influence on the glomic vasculature. A possible role of substance P contained in the endings of the carotid sinus nerve is discussed.

Animals↗

Preganglionic sympathetic fibres modulate dopamine turnover in rat carotid body during long-term hypoxia.

To assess the influence of sympathetic efferents on the dopamine function of carotid bodies, rats were exposed to long-term hypoxia (10% O2 in nitrogen for 1 or 3 weeks) after unilateral removal of the superior cervical ganglion. In the intact carotid bodies. long-term hypoxia increased the content and turnover of dopamine (DA). The dopaminergic response to hypoxia was reduced but not abolished by the ganglionectomy. To determine whether pre- or postganglionic sympathetic fibres are involved in the control of the dopamine function, rats were exposed to hypoxia either after unilateral transection of the preganglionic cervical trunk or after selective destruction of the postganglionic fibres by guanethidine. The preganglionic transection blunted the dopaminergic response to hypoxia whereas guanethidine had no effect. It is concluded that the sympathetic efferents may activate the synthesis and release of dopamine in glomus cells during long-term hypoxia. The sympathetic efferents responsible for the modulation of dopamine function are probably preganglionic fibres.

Animals↗

Oxygen uptake after major abdominal surgery: effect of clonidine.

To examine the effect of an alpha-2 agonist, clonidine, on oxygen uptake and on the incidence of postoperative shivering, 28 patients presenting for major abdominal surgery were randomly assigned in a double-blind manner to one of two groups. Intraoperatively, 14 patients received 5 micrograms.kg-1 clonidine infused over 3 h (clonidine group), and 14 patients received placebo (placebo group). Oxygen uptake was measured continuously over the first 3 postoperative hours with a mass spectrometer system. Circulatory variables, esophageal temperature, and skin temperature were measured over the first 6 postoperative hours. Heart rate, mean arterial pressure, rate pressure product, and norepinephrine concentration were decreased in the clonidine group (P less than 2 x 10(-4)). There were no differences among groups in the incidence of shivering and in the rate of increase of esophageal temperature. By contrast, oxygen uptake was lower in the clonidine group (P = 4 x 10(-4)). This contrasting pattern may be secondary to a reduction in the intensity of mean muscular tremor in the clonidine group.

Adjuvants, Anesthesia↗

Exercise endurance and fuel utilization: a reevaluation of the effects of fasting.

The effect of fasting on energy utilization during running or swimming was studied in adult male Wistar rats. Compared with fed rats, fasted animals displayed a decreased contribution of carbohydrates in energy supply, with decreased liver and muscle glycogen contents and decreased rate of glycogen breakdown. This was compensated by an enhanced rate of beta-oxidation. In addition, fasting induced an exaggerated sympathoadrenal response during exercise, reflected by a greater epinephrine plasma level and a higher norepinephrine turnover rate in both liver and soleus. Nevertheless, endurance capacity was similar in fasted and fed animals. These results contrast with the impairment of endurance observed in fasting humans but also with the improvement of endurance in rats previously reported by Dohm et al. (J. Appl. Physiol. 55: 830-833, 1983). These data suggest that the metabolic responses to exercise subsequent to food deprivation depend not only on the considered species but also, in the same species (rat), on the age of the animals and the duration of the fast. These factors probably determine the hormonal secretion and substrate utilization during prolonged exercise in fasting conditions.

Animals↗

Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma.

Urinary methoxyamine determination is considered as the most sensitive and specific parameter for the diagnosis of pheochromocytoma. Since blood sampling is easier to perform, we developed a new HPLC method to assay metanephrine (MN) and normetanephrine (NMN) in plasma. We now report the results for total (free and conjugated) MN and NMN in 22 cases of pheochromocytoma compared to 26 healthy subjects, 33 patients with essential hypertension, 14 with miscellaneous diseases and 4 patients with renal failure. The mean normal values (mean +/- SD) were 0.40 +/- 0.10 ng/ml for MN and 0.85 +/- 0.25 ng/ml for NMN. The sum of MN+NMN was 1.25 +/- 0.28 and the range 0.9-1.9. In essential hypertension, the range of NMN+MN was 1.2-6.0. In the 4 renal failures, both MN and NMN were drastically increased. In 49 samples drawn from 22 pheochromocytomas, MN was elevated over the hypertensive range in 34 samples and NMN in 47 samples. The total MN+NMN ranged from 6.2 to 436 ng/ml; this figure was observed whatever the clinical presentation even in silent tumors or in paroxysmal forms between the crisis. After tumor removal, the values dropped rapidly. In conclusion, plasma determination of MN and NMN provides a highly sensitive and specific biological pointer for the diagnosis of pheochromocytoma in patients without renal failure.

Adrenal Gland Neoplasms↗

Plasma free and sulphated catecholamines after ultra-long exercise and recovery.

We investigated the early and late effects of two types of ultra-long exercise on sympatho-adrenal and dopaminergic activity. With this aim both free and sulphoconjugated plasma catecholamines (CA), noradrenaline (NA), adrenaline (A), and dopamine (DA) were determined in two groups of athletes immediately after completion of 24-h running or a 10-h triathlon and on recovery during the next 1-3 days. Both races stimulated the sympathetic activity, but differences were observed in the CA pattern: the 24-h run induced a marked elevation of free and sulphoconjugated NA (+175% and +180%, respectively) but failed to alter significantly A and DA levels. The triathlon challenge increased the three conjugated CA (NA sulphate +350%; A sulphate +110%; DA sulphate +270%) and to a lesser extent free CA (NA +45%; A +30%). On the first post-exercise morning, a sustained intense noradrenergic activity was still present in the 24 h-runners, as evidenced by the large increase in free and sulphated NA levels (+140% and +100%, respectively). Such a prolonged activity was also indicated after completion of the triathlon, by the increase of NA sulphate (+140%) observed on the 1st recovery day. However, after the triathlon there was a decreased release of A from the adrenal medulla for several days. These data show that both types of ultralong exercise are able to induce for several hours a sustained sympathetic activation during the test and in the recovery period. Furthermore, the study shows that plasma conjugated CA may provide delayed and cumulative indexes of sympathetic activation, complementary to the instantaneous markers such as free CA.

Catecholamines↗

Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients.

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.

Adult↗

[Does Swan-ganz catheter help in weaning from controlled ventilation after mitral valve replacement?].

The difference between oxygen consumption during spontaneous and controlled ventilation represents the oxygen cost of breathing. Swan-Ganz catheters enable oxygen consumption to be calculated as the product of cardiac index by arteriovenous oxygen concentration. This method was used in 25 patients on the day after anaesthesia and mitral valve replacement to predict the success of weaning from mechanical ventilation. Four patients could not be weaned: one for pulmonary reasons, one for neurological reasons and two because of their cardiac status. Whether weaning was successful or not, oxygen consumption did not change significantly during spontaneous respiration; concomitantly lactacidaemia remained stable. Two patients had an oxygen consumption below the physiological threshold (115 ml.min-1.m-2): one could be weaned, but not the other. Haemodynamic parameters did not change significantly during weaning. Thus, measurement of oxygen consumption through a Swan-Ganz catheter does not predict the success of weaning after mitral valve replacement, but the catheter can diagnose a low cardiac output needing treatment before weaning.

Adult↗

Long-term hypoxia increases the turnover of dopamine but not norepinephrine in rat sympathetic ganglia.

The content and turnover of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine have been investigated in the superior cervical, coeliac and mesenteric ganglia of rats exposed to moderate normobaric hypoxia (10% O2 in N2) lasting for 2-28 days. the turnover was estimated by the decrease in amine contents after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. In all 3 sympathetic ganglia, long-term hypoxia elicited a sustained increase in the content and turnover of dopamine. In contrast, the content and turnover of norepinephrine remained unchanged, except for a moderate increase in the coeliac ganglion after 14 and 28 days of hypoxia. These results suggest that the dopamine and norepinephrine pools in ganglia have a different functional significance and that rat sympathetic ganglia contain a pool of dopamine specifically sensitive to long-term hypoxia.

3,4-Dihydroxyphenylacetic Acid↗

Differential effect of guanethidine on dopamine and norepinephrine pools in urine, heart and superior cervical ganglion in the rat.

The time-related changes of dopamine (DA) and norepinephrine (NE) pools were investigated in heart, superior cervical ganglion (SCG) and urine in rats treated chronically with guanethidine (50 mg/kg i.p. five days each week). The efficiency of sympathectomy was assessed by the great loss of NE in heart and superior cervical ganglion (SCG) (-96% and -76% respectively of control values on day 18) together with the ready reduction of NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine. The pattern of changes was quite different for DA, which was less readily affected and at a lesser extent than NE in heart and SCG thus suggesting the presence of norepinephrine-independent DA stores. Similarly the urinary excretion of free DA, free 3,4-dihydroxyphenylacetic acid (DOPAC) and free homovanillic acid (HVA) was slightly decreased only from the 9th day, whereas urinary conjugated DA remained unaltered. These results indicate that the greatest portion of urine free and conjugated DA, free DOPAC and free HVA derives from peripheral pools located outside noradrenergic neurons. Alternatively, the time-course of DA sensitivity to guanethidine suggests that a portion of urine DA may originate from DA stored independently from NE in noradrenergic neurons.

Animals↗

Dopamine and norepinephrine dynamics in rat carotid body during long-term hypoxia.

The contents of dopamine (DA), norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC), and the utilization rates (secretion plus breakdown) of DA and NE were measured in carotid bodies of rats exposed, to normobaric hypoxia (10% O2 + 90% N2) for 0, 2, 7, 14 or 28 days. Long-term hypoxia elicited gradual increase in DA, NE and DOPAC contents, which after 28 days were increased 27, 51 and 4.6 fold, respectively. The DA utilization rate estimated after blockade of biosynthesis by alpha-methyl-p-tyrosine gradually increased from two days to the end of hypoxic exposure. The utilization rate of NE was unaltered within the first 7 days but was greatly increased after 14 and 28 days. It was concluded that the utilization rates of both DA and NE were increased by long-term hypoxia but these increases had different time courses. Dopamine, whose utilization increased in the early stage of hypoxia, might exert neurochemical effects on the chemoreceptors throughout the exposure, whereas NE, whose utilization was stimulated after two weeks of hypoxia, might play a significant role only after a delay.

3,4-Dihydroxyphenylacetic Acid↗

Sustained enhancement of the catecholamine dynamics in rat carotid bodies, adrenals, sympathetic ganglia and target organs under long-term moderate hypoxia.

The effects of normobaric hypoxia (10% O2) for 2, 7, 14 and 28 days on the dopamine (DA), norepinephrine (NE) and epinephrine (E) dynamics (content and utilization) were investigated in carotid bodies, adrenals, heart, kidneys and three sympathetic ganglia. The results indicate that long-term hypoxia elicited a complex and sustained stimulation of the sympathoadrenal system. Four striking features were evidenced: 1) In carotid bodies, the DA, and with a delay, the NE dynamics were greatly enhanced; 2) in sympathetic ganglia, DA was the only catecholamine whose metabolism was enhanced, suggesting a chemosensitive DA pool in ganglia; 3) in nerve terminals (heart and kidneys), at variance with ganglia, the stimulation under hypoxia was evidenced by the increase in NE metabolic rate; 4) no adaptation of the sympathoadrenal activity occurred after 28 days of hypoxia, except, perhaps, for adrenals.

Adrenal Glands↗

Biochemical evidence for norepinephrine stores outside the sympathetic nerves in rat carotid body.

Adult rats were submitted to pharmacological or surgical sympathectomy. The chronic administration of guanethidine caused tremendous reductions in the norepinephrine stores in heart and superior cervical ganglion due to the destruction of the sympathetic nerve fibers and cell bodies. Guanethidine-sympathectomy resulted in a 70% loss of norepinephrine in the carotid body, whereas the dopamine and DOPAC contents were unaltered. The surgical sympathectomy induced by removing the superior cervical ganglion led to similar results. The present data indicate that a considerable part of norepinephrine in the rat carotid body is stored in the sympathetic nerves. In addition, a significant part of norepinephrine resides outside the sympathetic nerves, probably within the glomus cells.

3,4-Dihydroxyphenylacetic Acid↗