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Biomedical subjects

J M Cottet-Emard

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

At least 55 records · Page 3Linked to original sources

Hormonal, water balance, and electrolyte changes during sixty-day confinement.

The EXEMSI experiment has made it clear that it is difficult to perform psychological and physiological protocols satisfactorily in the same study. It is, therefore, essential that the objectives of study be defined clearly before the start. While behavioral and psychological studies may be possible and provide valid results for a small group of mixed gender, it is more difficult to conduct valid physiological studies due to large differences between individuals and even in the same individual over time. As stated before, it is unusual in space research on humans and even during space simulation studies to have large and homogeneous groups of subjects. The consequence is that the results remain tentative. For a better understanding of the physiological data collected during the ISEMSI ad EXEMSI experiments, they should be correlated with the results of the psychological studies. One of the conclusions drawn from the ISEMSI experiment was that confinement provides a valuable parallel to other simulations of weightlessness, such as bedrest. The same pattern of changes in parameters like the blood volume regulating hormones renin and aldosterone was observed as in bedrest. After the EXEMSI study we can say that the conditions imposed by confinement, high work load, and stress, potentiate these effects. This implies that in using head-down bedrest as a weightlessness simulation the confinement effects must be identified by setting adequate control conditions for the head-down position, for short-term as well as for long-term simulations. Indeed, we have seen in the two isolation studies that confinement may have its effects at the beginning of the isolation period (EXEMSI) as well as during the entire isolation period (ISEMSI). In planning for EXEMSI we wanted to obtain more insight in some of the phenomena observed during ISEMSI by the introduction of new techniques such as the doubly labeled water method for determination of total body water. However, in some cases the opposite effects of those encountered in ISEMSI were found. This was probably due to the many changes in the experimental scenario, like number of subjects, mixed gender, living space per subject, and workload. Thus, for future isolation studies the operational scenario should be better examined and preferably standardized. Nevertheless, in such studies as well as in long-term sojourns in a space station, the crew size will not be larger than that of the EXEMSI crew. Physiologists will, therefore, have to become familiar with the study of small groups of subjects and to try to overcome the problems of large individual differences and statistical analysis of data from small groups.

Adult↗

Effects of hypoxia on carotid body dopamine content and release in developing rabbits.

Hypoxia induces dopamine (DA) release from the carotid body (CB), but the role of DA during hypoxia in the postnatal maturation of carotid chemosensory discharge remains controversial. The aim of this study was to evaluate changes in CB content and release of DA evoked by hypoxia at different stages of development in the rabbit. Five groups of rabbits aged < or = 24 h (n = 9), 5 days (n = 27), 15 days (n = 18), 25 days (n = 16), and > or = 1 yr (n = 11) were studied. CBs were surgically removed and immediately incubated at 37 degrees C for 1 h in a surviving medium equilibrated with 100% O2 or 8% O2 in N2. The content of DA in the CB ([DA]CB) and the DA released in the surviving medium ([DA]r) were measured by high-performance liquid chromatography. [DA]CB was significantly larger in adults than in all pup groups in both 100% O2 [385.5 +/- 74.1 (SE) pmol/CB in adults and 43.6 +/- 6.0 pmol/CB in pups; P < 0.01] and hypoxia (518.1 +/- 99.9 pmol/CB in adults and 24.7 +/- 3.2 pmol/CB in pups; P < 0.01), presumably because of the larger CB mass. [DA]r was significantly larger in hypoxia than in 100% O2 only in 25-day-old rabbits (19.8 +/- 4.2 and 3.6 +/- 1.1 pmol/h, respectively; P < 0.01) and in adults (183.9 +/- 57.7 and 7.9 +/- 1.7 pmol/h, respectively; P < 0.01). The average ratio of [DA]r in hypoxia to [DA]r in 100% O2 ranged from 1.3 to 2.2 in the three younger age groups and was 5.5 and 23.3 in 25-day-old and adult rabbits, respectively. We conclude that the release of DA evoked by hypoxia is weak at birth and develops during the first weeks of life in rabbits.

Aging↗

Delayed increase of tyrosine hydroxylation in the rat A2 medullary neurons upon long-term hypoxia.

In vivo and in vitro activity of tyrosine hydroxylase (TH) was estimated in the catecholaminergic A2 cell group of the nucleus tractus solitarius (NTS) in rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 2 h, 3, 7, 14 or 21 days. The A2 cell group was subdivided into two subgroups. In the caudal A2 subgroup located caudal to the calamus scriptorius, long-term but not acute hypoxia elicited an increase of in vivo tyrosine hydroxylation rate after 7 days of exposure (+60% above normoxic controls). The increase of in vivo TH activity was maintained at the same level at the end of hypoxic exposure. In vitro TH activity was increased transiently after 7 days of hypoxia (+92% above normoxic (controls). In thr rostral A2 subgroup, hypoxia elicited a significant increase of in vivo tyrosine hydroxylation at 7 days (+38%) but did not alter in vitro TH activity throughout the whole exposure. Hypoxia produced no detectable change in TH activity in other noradrenergic cell groups of the brain stem (locus coeruleus, A5) except for a transient inhibition of in vivo TH activity in A5 after 2 h. Immunocytochemical analyses confirmed that the catecholaminergic neurons in the caudal A2 area are not only of a noradrenergic nature. The neurons were located in the commissural subnucleus of the NTS. On the other hand, the rostral A2 area contains noradrenergic neurons intermingled with a small number of adrenergic cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monoamines (noradrenaline, dopamine, serotonin) in the rat cochlear nuclei: endogenous levels and turnover.

Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and their metabolites, 3-methoxy,4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), were determined using high-performance liquid chromatography with electrochemical detection in the rat anteroventral cochlear nucleus (AVCN), in the dorsal part of the nucleus including the dorsal cochlear nucleus (DCN) and the posteroventral cochlear nucleus (PVCN) and as a comparison, in the locus coeruleus (LC) and dorsal raphe nucleus (RD) which contain the corresponding noradrenergic and serotonergic cell bodies. In both cochlear nuclei (CN), the endogenous levels of NA, 5-HT and related metabolites were smaller than in LC or RD. NA turnover assessed from the ratio MHPG/NA or after treatment with alpha-methylparatyrosine was faster in the CN than in LC; in contrast, 5-HT turnover was lower in the CN than in RD as shown by the ratio 5-HIAA/5-HT. In agreement with previous histological findings, NA and 5-HT were more concentrated in AVCN than in DCN+PCVN; however, the turnover of both monoamines was faster in the dorsal nuclei. In addition, the CN contained small amounts of dopamine and DOPAC; both DA levels and the ratio DA/NA (0.10 vs. 0.04) were greater in the dorsal than in the ventral part suggesting the presence of non-precursor-specific DA pools. Our data suggest that the functional involvement of monoamines may be different in cochlear subnuclei.

Animals↗

Spectral analysis of stress-induced change in blood pressure and heart rate in normotensive subjects.

Changes in spectral analysis of the variability in systolic blood pressure (SBP) and heart rate (HR) were investigated in 12 normotensive volunteers during a well-standardized stress test. BP was measured indirectly from the finger by a noninvasive device (Finapres). The stress test was a computerized version of the Stroop color word conflict test (CWT). The influences of acute (single dose) beta 1-selective blockade by bisoprolol or angiotensin-converting enzyme (ACE) inhibition by lisinopril were analyzed by a double-blind placebo-controlled trial. During the placebo phase, the efficiency of the stress test was confirmed by a significant increase in SBP (25 +/- 11%), HR (36 +/- 23%), and plasma concentrations of epinephrine (Epi, 54 +/- 37%) and norepinephrine (NE, 27 +/- 35%). Stress induced a significant increase in the amplitude of SBP and HR oscillations in the medium-frequency band (MF, 70- to 140-mHz range), which corresponds to the Mayer waves (27 +/- 32 and 42 +/- 43%, respectively for SBP-MF and HR-MF). The stress-induced increase in NE correlated significantly with the increase in HR (r = 0.68, p < 0.05). The stress-induced increase in SBP-MF correlated significantly with the increase in Epi (r = 0.69, p < 0.05) and in HR-MF (r = 0.69, p < 0.05). A significant decrease in SBP-MF at rest was observed with a single oral (p.o.) dose of bisoprolol, but not of lisinopril. As a noninvasive method, spectral analysis of the variability in SBP and HR may be of benefit in stress-induced modifications of the autonomic nervous system.

Adult↗

Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness.

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.001) and caudal (-73%; P < 0.001) A2 nucleus of suspended rats but was unchanged in the A1, A5, and A6 cell groups compared with attached rats. The NE turnover in the cardiac atria (-34%; P < 0.001) and ventricles (-35%; P < 0.001) and kidneys (-31%; P < 0.001) was decreased after suspension. The central and peripheral sympathetic activities returned to normal within 24 h of release from suspension, but there was hyperactivity after 6 h of recovery. This raises the problem of interpreting the results obtained in animals killed a few hours after return from spaceflight.

Animals↗

Comparison of the effects of spaceflight and hindlimb-suspension on rat pituitary vasopressin and brainstem norepinephrine content.

To compare actual spaceflight to ground-based simulation (hindlimb-suspension), we measured the norepinephrine (NE) content in A1, A2, A5 and A6 (locus coeruleus) and the vasopressin content in the neurohypophysial system. The experimental period was of 9 days' duration. The NE content in the locus coeruleus decreased significantly in rats flown for 9 days (67%, p < 0.001), but showed no significant changes after hindlimb-suspension. These results demonstrated that suspended rats adapted better to weightlessness-simulation than flown rats to actual microgravity. In rats flown aboard SLS-1, the vasopressin content was significantly increased in the posterior pituitary (71%, p < 0.01), and was decreased in the hypothalamus (49%, p < 0.05). In 9-day suspended rats pituitary vasopressin levels were unchanged, while in the hypothalamus a significant decrease was noted (21%, p < 0.05). It was concluded that spaceflight changes in pituitary vasopressin levels and in the locus coeruleus NE content were consistent with a stress reaction, occurring during and/or after landing. These results confirmed that hindlimb-suspension model constitutes a valid and less stressful [correction of lesstressful] ground-based simulation of microgravity in rats.

Animals↗

Fluid-regulating and sympathoadrenal hormonal responses to peak exercise following cardiac transplantation.

Orthotopic heart transplantation results in cardiac denervation that can disrupt the normal regulation of hydromineral balance. This study compared the exercise-induced variations in plasma osmolality; atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (E), and dopamine (DA) concentrations; and plasma renin activity (PRA) of six cardiac transplant recipients (HTX) and six healthy age-matched controls (C) submitted to graded upright maximal cycling. Venous blood samples were obtained at rest, at submaximal (70% O2 uptake) and peak exercise, and after 10 and 30 min of sitting recovery. Peak O2 uptake was not different between groups despite lower maximal heart rate in HTX (136 +/- 6 vs. 183 +/- 9 beats/min). Baseline plasma ANP and PRA were higher in HTX (203 +/- 55 pg/ml and 29.9 +/- 7.4 ng.ml-1 x h-1) than in C (71 +/- 17 pg/ml and 5.4 +/- 0.96 ng.ml-1 x h-1); AVP was lower in HTX than in C (1.1 +/- 0.3 vs. 3.2 +/- 0.8 pg/ml; P < 0.05); and circulating E, NE, and DA were not different between groups. Exercise resulted in more marked increases in HTX than in C for ANP (300 vs. 100%), AVP (2,000 vs. 300%), NE (860 vs. 500%), and DA (611 vs. 187%) but not for PRA and a higher E response in C than in HTX (455 vs. 1,258%). These observations confirm that the potential for ANP release to central volume loading is independent of intact cardiac innervation. The exaggerated AVP response in HTX could, however, reflect the absence of inhibitory influences consecutive to denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Adrenal response to long-term hypoxia is still increased after carotid body denervation in rat.

This study investigated the effects of long-term normobaric hypoxia (10% O2 in N2 for 2, 7, 14, and 28 days) on the metabolism of catecholamines in rat adrenals and the role of the carotid body chemoreceptors in the adrenal response. The content and utilization of dopamine were significantly increased from the 7th day of hypoxia and remained enhanced thereafter. The content of norepinephrine and epinephrine decreased after 2 days of hypoxia and increased thereafter; after 28 days of hypoxia the norepinephrine amounts remained enhanced but the epinephrine levels were no longer significantly increased. In vivo tyrosine hydroxylation increased after 7 days of hypoxia. Bilateral transection of the carotid sinus nerve 1 wk before hypoxia failed to abolish the increase in the content and utilization of dopamine after 7, 14, or 21 days of hypoxic exposure. These results indicate that long-term normobaric hypoxia elicits a long-lasting increase in the metabolism of catecholamines in adrenals, especially as assessed by dopamine measurement, and that this response does not involve a carotid body chemoreflex pathway.

Adrenal Glands↗

[Plasma methoxyamines assay: a practical advance for the diagnosis of pheochromocytoma].

Measurement of plasma methoxyamines is aimed to provide a reliable plasma marker readily available for any patient suspected of having a pheochromocytoma. The present HPLC method is able to detect methoxyamine amounts as low as 0.2 nmoles/l and allows the determination of both free or conjugated methoxyamines (metanephrine MN and normetanephrine NMN) in normal subjects, treated or untreated patients and a fortiori in pheochromocytoma. The analytical specificity is excellent. Among most usual antihypertensive drugs, only conversion enzyme inhibitors and diuretics induce in some patients a moderate increase of NMN with minor consequence in values interpretation. The kidney plays a major role in the blood clearance of methoxyamines and any alteration of renal function is associated to the increase of plasma methoxyamine levels. Plasma methoxyamines have a long half-life and are long-lasting integrated markers of catecholamine secretion; at variance with plasma free catecholamines, they are able to afford the presence of a secreting pheochromocytoma whatever the clinical presentation--asymptomatic or paroxysmal form between the crisis. The diagnostic sensitivity (at least 98%) is equal to that of urinary methoxyamines, far higher than plasma or urine catecholamines or urine VMA (60 to 70%).

Adrenal Gland Neoplasms↗

Effects of a short term hindlimb suspension on central and peripheral norepinephrine turnover in rats.

The loss of appropriate cardiovascular reflexes which contributes to the cardiovascular deconditioning observed after an exposure to actual or simulated microgravity (in man or animals) is well known, but the mechanisms responsible remain unclear. This protocol, a 2.5 h hindlimb suspension in rats, was undertaken to study the early adaptation of the sympathetic neurons involved in arterial pressure regulation: we determined central norepinephrine (NE) turnover in the brainstem catecholaminergic cell groups responsible for the central cardiovascular regulation i.e. A1, A2 (rostral and caudal), A5 and A6 cell groups and peripheral NE turnover in target organs (heart and kidneys). The NE turnover in suspended rats significantly decreased in rostral A2 (48% p < 0.001), caudal A2 (52% p < 0.001) and A5 (40% p < 0.05) cell groups while it was unchanged in A1 and A6 cell groups compared with rats attached to the suspension device but maintained in the horizontal position. The short term hindlimb suspension did not alter the NE turnover in cardiac atria and ventricles or in kidneys nor did it alter the blood variables studied (hematocrit, osmolality, plasma sodium, potassium, proteins and renin concentration). We concluded that a 2.5 h hindlimb suspension reduced noradrenergic neuron activity in A2 and A5 cell groups involved in the central control of arterial pressure and particularly in the baroreceptor reflex mechanisms. This duration was probably not sufficient to modify the NE turnover in the two peripheral organs studied.

Animals↗

European isolation and confinement study. Blood pressure, volume-regulating hormones, and electrolytes.

In the ISEMSI confinement experiment we observed three main reactions concerning blood volume regulation: first, a stress activation produced by the high workload that the subjects had to accomplish, both before the isolation period and during the two first weeks of isolation; second, a typical defense reaction to the environment occurred, at least during the two initial days of isolation and later perhaps between crew members themselves; and third, a change in blood volume regulating hormone levels may have been the result of the increase of sympathetic system activity and of dehydration. Confinement is certainly a good and valid method to simulate space station life (with the absence of weightlessness). So, it is interesting to use these confinement studies to perform biological and physiological experiments to obtain greater knowledge, but also to prepare and validate new scientific protocols or new scientific equipment suitable for spaceflights. Even more so, confinement is a good way to prepare and train crew members for long-term space missions. It would seem desirable to confirm the scientific results obtained during the ISEMSI campaign, and especially those for the regulation of the blood volume. This will be done during the next confinement experiment, called EXEMSI, in which four subjects will be subjected to 60 days of confinement.

Adult↗

Norepinephrine content in discrete brain areas and neurohypophysial vasopressin in rats after a 9-d spaceflight (SLS-1).

The norepinephrine (NE) content in discrete brain areas and the vasopressin content in the neurohypophysial system were assessed in rats after a 9-d spaceflight and after a recovery period (9 d). The NE content in the locus coeruleus decreased significantly in spaceflight rats (2.9 +/- 0.3 vs. 8.9 +/- 0.7 pmol.structure-1 for control rats, p < 0.001), but showed no difference between control and flight animals after a 9-d recovery. These findings were probably due to an acute stress undergone during landing. The NE content was unchanged in the A2 and A5 cell groups. In rats flown aboard SLS-1, the vasopressin content was increased in the posterior pituitary (1.47 +/- 0.1 vs. 0.86 +/- 0.1 micrograms.structure-1, for control rats, p < 0.01), and was significantly decreased in the hypothalamus (8.95 +/- 2.0 vs. 17.6 +/- 2.2 ng.structure-1, for control rats, p < 0.05). We conclude that the NE depletion in the locus coeruleus and the alteration in vasopressin release were consistent with an acute stress, likely occurring during and/or after landing. These changes tend to mask the actual neuroendocrine modifications caused by microgravity.

Animals↗

Central and peripheral norepinephrine turnover after hindlimb suspension in the rat.

After a 9-d hindlimb suspension, the turnover rate of norepinephrine (NE) in rats was determined in A1, A2 (rostral and caudal), A5 and A6 cell groups, as well as in peripheral target organs (heart and kidneys). The NE turnover rate decreased after hindlimb suspension respectively in caudal A2 (67.5%, p < 0.001), rostral A2 (63%, p < 0.001) and in A5 cell groups (62.5%, p < 0.001), but remained unchanged in A1 and A6 regions. The peripheral sympathetic outflow response was selectively modified: in suspended rats, the NE turnover was mainly decreased in atria (79%, p < 0.001) and in ventricles (44%, p < 0.001); there were no biochemical changes in kidneys. It was concluded that a 9-d hindlimb suspension: 1) impaired the noradrenergic neuron activity of A2 and A5 cell groups, which are involved in the central cardiovascular regulation, and particularly in the baroreceptor reflex mechanism; and 2) mainly altered the cardiac NE turnover and induced a selective response of peripheral target organs.

Animals↗