Search PubMed⌕ Search

Biomedical subjects

C Gharib

Publications and source records attributed to C Gharib.

At least 91 records · Page 5Linked to original sources

Restraint vs. hindlimb suspension on fluid and electrolyte balance in rats.

To determine the effect of hindlimb suspension on body fluid volume, salt and water balance, and relevant hormones, two series of experiments were performed in an experimental protocol including periods of isolation (7 days), horizontal attachment (7 days), and suspension (14 days). 1) During the first experiment, water and electrolyte balance, arginine vasopressin (AVP), and guanosine 3',5'- cyclic monophosphate (cGMP) were determined in urine, atrial natriuretic peptide in plasma and atria, and renin concentration and AVP in plasma in 30 rats. 2) During the second experiment, blood volume and extracellular fluid volume were measured by a dilution technique (Evans blue and sodium thiocyanate) in another 30 rats. We observed a pronounced and early effect of horizontal attachment on the renal variables. After 48 h, diuresis (49%), natriuresis (44%), kaliuresis (36%), osmotic load (39%), creatinine (28%), and AVP excretion (155%) were significantly increased in attached rats (P < 0.05). There was no short-term (24-h) effect of suspension on urine flow and Na+, K+, creatinine, and AVP excretion, but the urine cGMP decreased significantly (45%; P < 0.05). Significant decreases in natriuresis, kaliuresis, urine creatinine, and osmotic load occurred in the suspension group 7 days after suspension. After the 14-day tail suspension, plasma volume and extracellular fluid volume measured in suspended rats were not different from isolated rat values, whereas plasma volume increased by 15% (P < 0.05) in the attached rats. Plasma immunoreactive plasma atrial natriuretic levels of suspended rats were significantly reduced by 35% vs. isolated rats (P < 0.001) and by 18% vs. attached rats (P < 0.05). By using this experimental protocol, the physiological alterations revealed that suspension produced some acute and long-term effects, but the fixation to the suspension device, restraint, and confinement have their own influence on fluid distribution and renal function.

Animals↗

Erythropoietin under real and simulated microgravity conditions in humans.

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

Adult↗

Cardiovascular and hormonal response during a 4-week head-down tilt with and without exercise and LBNP countermeasures.

To determine whether exercise and Lower Body Negative Pressure (LBNP) during 28 days of -6 degrees head-down tilt (HDT) would modify orthostatic tolerance and blood volume regulating hormones, twelve healthy men were assigned to either a no- countermeasure (No-CM, n=6), or a countermeasure (CM, n=6) group. LBNP sessions consisted of 15 minutes exposure to -30 mm Hg, on days 16, 18, 20 and 22-28 of HDT. Muscular exercise began on day 8 and consisted of combined graded dynamic and isometric resistance bilateral leg exercise on a specially designed supine ergometer, in two sessions of 15-20 min. each, every day, 6 days per week. A tilt test was performed before and at the end of HDT. Changes in resting plasma volume from control day (D-5) to HDT day 24 were -11.2% for No-CM and -2.2% for CM. After HDT three among the 6 subjects of the No-CM group presented presyncopal or syncopal symptoms, no tilt test was interrupted in CM group. Atrial Natriuretic Peptide (ANP) decreased at day 7 for the two groups and remained low during all the HDT period for No-CM group only. Plasma Renin Activity and Aldosterone increased at day 7 and remained elevated for the two groups. Norepinephrine and epinephrine were unchanged. Elevated diuresis and natriuresis were evident during the first day of HDT. However, renal excretory patterns were different between the two groups: indeed, a decrease of Na+, ANP and cGMP was observed only in No-CM at Day 13 during HDT. Our data showed that the subjects of the No-CM group experienced a greater increase in heart rate and a decrease in systolic blood pressure during tilt tests after HDT; nevertheless, after HDT, blood pressure was better maintained in CM group during the tilt test. The plasma volume decrease measured at the end of HDT was significantly lower in CM group, in contrast, these countermeasures were ineffective in preventing at least certain changes in blood volume regulating hormones.

Adult↗

Cortico-adrenal function under simulated weightlessness during gestation in the rat--effects on fetal development.

To examine the effects of simulated weightlessness on cortico-adrenal function and on fetal development, we suspended pregnant rats for 20 days. The levels of adrenal and plasma corticosterone were examined in mothers and in fetuses. The animal control group was kept single in standard cages. Growth of the suspended animals was repressed for the first 8 days of the experiment, but thereafter it increased greatly, as did the daily food intake. By the 18th day of the experiment, the body masses and food intake of the two groups were equal. No modification in circulating corticosterone was found. It appears that there is no stress in pregnant rats submitted to simulated weightlessness.

Adaptation, Physiological↗

Central and peripheral noradrenergic responses to 14 days of spaceflight (SLS-2) or hindlimb suspension in rats.

INTRODUCTION: The purposes of this work were to assess the influence of microgravity on the central and peripheral noradrenergic activity to reevaluate SLS-1 mission findings and to compare it with that of simulated microgravity in rats. METHODS: The norepinephrine (NE) contents of the brainstem cell groups (A1, A2, A5, and A6) and organs (heart and kidneys) involved in blood pressure regulation were determined in rats after a 14-d spaceflight (SLS-2 with animals sacrificed 6 h after landing) and after a 14-d hindlimb suspension followed with 6 h of recovery. RESULTS: After SLS-2 spaceflight, NE contents were not significantly different between flight and ground-based rats either in A1 (5.2 +/- 0.5 vs. 5.7 +/- 0.4 pmol/structure), rostral A2 (12.1 +/- 0.5 vs. 11.1 +/- 0.9 pmol/structure), caudal A2 (3.2 +/- 0.6 vs. 4.3 +/- 0.5 pmol/structure) and A5 (4.4 +/- 0.4 vs. 4.3 +/- 0.5 pmol/structure) nuclei or in cardiac atria (98.6 +/- 7.5 vs. 83.4 +/- 8.9 pmol.mg-1 protein), ventricles (38.3 +/- 2.2 vs. 44.1 +/- 2.8 pmol.mg-1 protein) and kidneys (13.4 +/- 0.8 vs. 17.7 +/- 1.5 pmol.mg-1 protein). NE content was unchanged in A6 nucleus after SLS-2 comparing with control rats (respectively 4.1 +/- 0.3 vs. 4.5 +/- 0.5 pmol/structure), while it was depleted after SLS-1 mission (2.9 +/- 0.3 vs. 8.8 +/- 0.7 pmol/structure, p < 0.001) probably in relation with the stressful conditions on return to Earth. Similarly, no alterations between suspended and control rats were noted in central and peripheral NE contents after 14 d of suspension and after 6 h of recovery, whereas NE turnover studies evidenced large changes in the activities on structures on suspension and on recovery. CONCLUSION: These results suggest that only NE turnover determination will provide information about the role of the sympathetic system in the cardiovascular deconditioning. This raises the problem of the necessity to experiment inflight (injections, sacrifice) in order to avoid the recovery effects of the few hours following the landing.

Animals↗

Blood volume regulating hormones response during two space related simulation protocols: four-week confinement and head-down bed-rest.

The volume of regulating hormones (renin, aldosterone, arginine vasopressin and atrial natriuretic factor), electrolytes and creatinine concentrations, and blood pressure were measured in two different four-week experimental protocols: respectively -6 degrees head-down bed-rest (5 subjects) and confinement (6 subjects). We observed a significant increase (P < 0.01 at D2 vs D-5) of systolic blood pressure during confinement and a different level of response for some hormones, especially for arginine vasopressin (300% increase during confinement instead of 50% during bed-rest). The renin-angiotensin-aldosterone system was enhanced during confinement and head-down bed-rest. In both conditions, we obtained a similar pattern of response for blood volume regulating hormones. During confinement, two main factors were inactivity and stress activation of the sympathetic nervous system. In the bed-rest study the response is principally due to the fluid shift and blood volume adaptation but it is not possible to exclude the role of inactivity and stress.

Adult↗

Central cardiovascular effects of acetylcholine in the conscious dog.

1. The effects of central cholinomimetic drugs on cardiovascular and vasoactive hormonal responses (blood pressure, heart rate, catecholamines, vasopressin, atrial natriuretic factor, neuropeptide Y plasma levels and plasma renin activity) were investigated in conscious Beagle dogs. For this purpose a catheter was chronically implanted into each dog's cisterna magna to allow repeated central injections in the awake animals. 2. Intracisternal acetylcholine (20 micrograms kg-1) significantly increased systolic and diastolic blood pressure. These changes were accompanied by an initial short term tachycardia followed by a long lasting bradycardia. Intracisternal acetylcholine also increased noradrenaline, adrenaline and vasopressin plasma levels, decreased plasma renin activity but did not modify plasma levels of neuropeptide Y and atrial natriuretic factor. 3. The effects of acetylcholine were completely abolished by pretreatment with intracisternal injection of the muscarinic antagonist, atropine (5 micrograms kg-1) but not by the intracisternal injection of the nicotinic antagonist, mecamylamine (25 micrograms kg-1). 4. The present results demonstrate that there are qualitative and quantitative differences between the central cardiovascular effects of acetylcholine in conscious dogs compared to what we previously reported, using a comparable protocol, in anaesthetized dogs. Under both conditions, we observed a central cholinergically mediated increase in blood pressure secondary to an increase in sympathetic tone and vasopressin release but these responses were shorter (less than 10 min) in the conscious dogs than in anaesthetized dogs (more than 10 min). Moreover, we detected in the response to the central cholinergic stimulation in the conscious dogs a significant increase in plasma adrenaline levels and biphasic changes in heart rate which were not described previously in the anaesthetized dog.

Acetylcholine↗

Investigation of hormonal effects during 10-h head-down tilt on heart rate and blood pressure variability.

Head-down tilt (HDT) bed rest was used in this study to achieve physiological manipulation of the plasma concentrations of atrial natriuretic peptide (ANP) and the hormones of the renin-angiotensin system. The purpose of this was to achieve a parallel with previous animal experiments in which blockade of the renin-angiotensin system caused significant increases in low-frequency spectral power of heart rate variability, presumably as a consequence of increased blood pressure variability, although this was not measured in these animal experiments. Eight healthy young men completed 10 h of seated control and 6 degrees HDT. To gain a more complete understanding of the interactions between hormonal and neural factors involved in cardiovascular regulation, we measured heart rate, systolic and diastolic pressure variabilities, plasma hormone concentrations, and blood flow to selected vascular beds by pulsed Doppler. Resting R-R interval was not significantly different between seated and HDT tests. Stroke volume and cardiac output were elevated in the first 1-2 h of HDT (P < 0.05), whereas each of systolic (P < 0.01) and diastolic (P < 0.0001) pressures was lower during HDT. Plasma ANP increased as much as 70% during HDT (P < 0.0001). Total variability in each of R-R interval and diastolic blood pressure was reduced during HDT (P < 0.001). Thus, at a time when plasma renin activity was decreased as much as 40% (P < 0.0001), there was in fact a decrease in the variability of R-R interval and diastolic blood pressure in contrast to the hypothesized increase such as found in previous animal experimentation. The data were compatible with tighter autonomic regulation of heart rate about the ideal mean value during HDT.

Adult↗

Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats.

To verify whether a long-term weightlessness simulation was associated with development of cardiovascular deconditioning, male Wistar rats were tail suspended for 13 days and then removed for a 24-h recovery. Blood pressure (BP) and heart rate (HR) responses, their spectral properties, and the pharmacologically tested baroreceptor reflex sensitivity were studied throughout the suspension period and after removal from the tail suspension device. BP, HR, and their variability were not altered over the experimental period, and there were no indications of orthostatic intolerance on release from head-down suspension. Spectral properties of BP and HR were unchanged during the experiment, and tail suspension did not induce modifications in the baroreceptor reflex sensitivity. These results taken together suggest that cardiovascular deconditioning may not be developed even after long-term hindlimb suspension in rats, in contrast to humans exposed to actual or simulated weightlessness. Our results raise issue with the use of tail-suspended rats as a valid model for the study of alterations in cardiovascular function induced by spaceflight in humans.

Animals↗

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↗

Spectral analysis of blood pressure variability in heart transplant patients.

The cardiac transplant patient provides a unique model for the study of blood pressure variability in the absence of heart rate variability. We examined the harmonic and fractal components of blood pressure variability in 14 heart transplant patients (12 men, 2 women; 21 to 62 years of age) and in age-and sex-matched control subjects during seated rest, supine rest, and supine rest with fixed-pace breathing (12 respirations per minute). Heart rate was faster in transplant patients than in control subjects, with much less heart rate variability (P < .0001). Spectral analysis of blood pressure variability revealed no difference in total power for either systolic or diastolic pressure, but transplant patients had less low-frequency (0 to 0.15 Hz) harmonic spectral power in both systolic (P < .01) and diastolic (P < .03) pressure and more high-frequency power (0.15 to 0.5 Hz) in diastolic pressure than control subjects. The ratio of high-frequency power in diastolic relative to systolic pressure was consistently higher (P < .0001) in the transplant patients (0.29 to 0.51) than in control subjects (0.11 to 0.13). The slope of the fractal component of systolic pressure was approximately 1.8 in both transplant patients and control subjects. This was greater than the slope for heart rate variability (approximately 1.1 in control subjects). These data provide clear evidence of independence of the fractal component of heart rate and blood pressure variabilities in both transplant patients and control subjects. The heart rate component of the arterial baroreflex minimized high-frequency diastolic pressure changes while contributing to low-frequency variations in both systolic and diastolic pressures.

Adult↗

[Involvement of urodilatin in the hydro-electrolytic modifications induced in man by a 6 degree head-down tilt].

On 6 healthy men, we measured: 1/ the effects of 28-day -6 degrees head-down tilt on the excretion of urodilatin and 2/ the relationship between urodilatin and urinary fluid, or sodium excretion. Aliquots of the pooled 24-h urine output were used. Urodilatin increased parallel to urinary fluid or Na+ at first day of head-down tilt. Positive and statistically significant linear correlations could be established between urodilatin (and ANP) and urinary volume, or Na+ in five subjects on six. Urodilatin might participate as one of the several mechanisms of diuresis and natriuresis of first hours of head-down tilt.

Adult↗

Variability and cardiovascular homeostasis.

The inability to maintain the upright posture due to a failure in the arterial blood pressure regulatory mechanisms on return from space travel or after a period of head down tilt bed rest (HDBR) is the ultimate sign of cardiovascular deconditioning. Yet, the final response of syncope is potentially heralded by a series of precursor events that can be quantified and analyzed in new, more insightful ways to attempt to understand the integrative nature of autonomic control of the cardiovascular system.

Baroreflex↗

Hormonal regulation during a 60-day confinement (ESA-EXEMSI'92) in humans.

EXEMSI'92 was a 60-day isolation and confinement experiment with an international crew. During this second experiment of the European Space Agency (the first one was a 28-day confinement with 6 men: ISEMSI'90), blood volume regulating hormones and water balance were studied. During ISEMSI'90, stress level was elevated as shown by specific markers and we observed some interesting results which have been already observed before, during bed-rest experiments. Thus, our conclusion was that some of the physiological effects observed during bed rest could be the consequence of the "confinement effect" and/or stress imposed to the subjects during such experiments. The aim of the present physiological study was: 1/to define the origin of the blood pressure increase seen during ISEMSI'90; 2/ to study the blood volume regulating hormones (ANP, renin, aldosterone) variations; 3/ to determine the dehydration level by measuring the total body water with the doubly labeled water (DLW) method and fluid balance in general.

Aldosterone↗

Early and late renin and ANP modifications induced by bedrest.

A number of studies have been devoted to better understand the cardiovascular adaptation to space flights. These studies included hemodynamic and hormonal studies, but few investigations of the rhythms exist in the literature. However, the importance of the modifications of rhythms in true or simulated weightlessness was underlined in some published works. Several factors are probably associated to modify the circadian rhythms. First, there is a reduction or an absence of gravity, an important environmental factor: second, space missions or bed rest simulations are conducted under confinement conditions which may influence many psychological functions. The resulting instability of the circadian state will affect other physiological systems, because circadian variations are a fundamental feature of many biological systems (sleep, endocrine and cardiovascular functions). The present study was undertaken to study the effect of as well as a continuous 28-day bed rest on the rhythms of circulating PRA and ANP, the modification of rhythmicity of systolic and diastolic blood pressure and heart rate during bed rest.

Atrial Natriuretic Factor↗

Effects of 28-day head-down tilt with and without countermeasures on lower body negative pressure responses.

This study was performed to determine the effects of 28 d of head-down tilt (HDT) (simulated weightlessness) on cardiovascular responses to orthostatic stress induced by lower body negative pressure (LBNP) (before, during, and after HDT) and +60 degrees head-up tilt (before and after HDT) in 12 subjects. Half of them underwent countermeasures (CM) of regular muscular exercise (isometric and isokinetic training) and LBNP sessions (-30 mm Hg) as generally performed during spaceflight; the other six were a control group (C). The countermeasure effect on the orthostatic responses to LBNP and tilt test was assessed by studying the changes after HDT in the two groups. Essentially, blood pressure was better maintained in group CM in the tilt test after HDT (MBP at the end of the tilt vs. baseline value: +16% (CM); -19% (C)). LBNP and muscular exercise may have contributed to this improvement. One of the probable contributing factors is the relative conservation of plasma volume, at the end of HDT, in group CM (-2.2%), compared to group C (-11.2%). Transcranial Doppler (TCD) recordings of middle cerebral artery (MCA) velocities permitted indirect evaluation of cerebral blood flow changes during the orthostatic tests. MCA velocities decreased significantly although slightly (-7 to -12%) during LBNP sessions without changes along the HDT showing that the cerebral circulation was well preserved in each group. On the other hand, subjects undergoing presyncopal symptoms presented a drop in MCA velocities, suggesting a decrease in cerebral blood flow.

Adult↗

[Orthostatic hypotension after space flight].

Cardiovascular changes occur during spaceflight. Because of the loss of hydrostatic pressure there is, during weightlessness, a fluid shift of extra- and intra-vascular volumes to the upper part of the body. This provokes objective and subjective symptoms, especially in the first days of spaceflight. The fluid shift is perceived by baroreceptors as a relative central hypervolaemia and induces neuro-hormonal mechanisms which provoke a real hypovolaemia. Cardiovascular deconditioning exists during spaceflight with the following symptoms when astronauts return to earth: decreased orthostatic tolerance with possible tendency towards spontaneous syncope and decreased effort capacity. The mechanisms of orthostatic intolerance are not well known. Several factors are probably involved, including hypovolaemia, modifications of the venous system, baroreflex changes, etc. Various countermeasures have been tested in microgravity simulations on the ground, then in flight.

Cardiovascular Deconditioning↗