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C Gharib

Publications and source records attributed to C Gharib.

At least 37 records · Page 2Linked to original sources

Are energy metabolism alterations involved in cardiovascular deconditioning after weightlessness? An hypothesis.

The physiopathogenesis of the cardiovascular deconditioning syndrome observed after actual and simulated microgravity is still under debate, despite numerous studies conducted on the role of blood volume, hormones involved in its regulation, sympathetic nervous system, baroreflexes and venous compliance. Orthostatic intolerance, a reduced exercise capacity and an increased heart rate at rest characterize this syndrome. Recent data suggest, first, the presence of a complex loop between the sympathetic nervous system, carbohydrate metabolism (insulin) and leptin hormone and, second, that this loop, an overall reflection of energy metabolism, participates in cardiovascular regulation. After a resume of studies conducted on fuel homeostasis during actual and simulated microgravity, the possible implications of energy metabolism in the development of the cardiovascular deconditioning syndrome will be discussed.

Adaptation, Physiological↗

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest.

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head-down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio-cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head-down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head-down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: -201 +/- 37 mL vs. control: -345 +/- 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head-down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head-down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.

Adult↗

Renal blood flow measurement by positron emission tomography using 15O-labeled water.

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Animals↗

Adaptations to a 7-day head-down bed rest with thigh cuffs.

PURPOSE: Thigh cuffs were two elastic strips fixed at the upper part of each thigh, which limits the shift of fluid from the legs into the cardio-thoracic region. The purpose of this study was to examine the effects of thigh cuffs on hormonal and plasma volume responses and orthostatic tolerance during a 7-day head-down bed rest (HDBR). METHODS: Orthostatic tolerance, plasma volume, total body water, blood volume-regulating hormones, and hydro-electrolyte responses were measured in eight healthy men (age range, 25-40 yr), using thigh cuffs 10 h daily during 7 d of -6 degrees HDBR. RESULTS: Thigh cuffs worn during HDBR attenuated the decrease in plasma volume observed after HDBR (thigh cuffs: -5.85 +/- 0.95% vs control: -9.09 +/- 0.82%, P < or = 0.05). During this experiment, there was no significant change in total body water. Thus, the hypovolemia did not result from a loss of water but from a fluid shift from the blood compartment into the interstitial and/or intracellular compartment. Hormonal responses during HDBR and stand test were not modified by the thigh cuffs. Thigh cuffs had no significant effect on the clinical symptoms of orthostatic intolerance after HDBR. CONCLUSIONS: Thigh cuffs worn during HDBR blunted the decrease in plasma volume but did not reduce orthostatic intolerance; thus, they are not a completely effective countermeasure. Furthermore, hypovolemia seems to be necessary but not sufficient to induce orthostatic intolerance after HDBR.

Adult↗

Leptin responses to physical inactivity induced by simulated weightlessness.

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on alternating days in females (n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.

Adult↗

Validation of the doubly labeled water method in rats during isolation and simulated weightlessness.

Total energy expenditure (TEE) of rats during simulated microgravity is unknown. The doubly labeled water method (DLW) reliably measures TEE, but the results depend on the methods of calculation. These methods were validated and appraised by indirect calorimetry in eight rats during isolation (7 days) and simulated microgravity (10 days). There were no effects on CO(2) production in the method used to derive constant flux rates as in the regression models. r(CO(2)) estimates were dependent on the assumed fractionation processes, the derivation of constant flux rate methods, and the selected pool models. Use of respiratory or food quotients did not influence TEE estimations, which were similar during isolation and simulation. During either isolation with growth or simulation with a stabilized mass, the one-pool model of Speakman (Speakman JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) resulted in the more reliable validation (0.8 +/- 2.2 and 2.2 +/- 3.4% vs. calorimetry, respectively). However, during simulation, agreement was also observed with the single pool model of Lifson (Lifson N, Gordon GB, and McClintock R. J Appl Physiol 7: 704-710, 1955) (-2.5 +/- 2.5%), and two two-pool models [Schoeller (Schoeller DA. J Nutr 118: 1278-1289, 1988) (0.5 +/- 3.1%) and Speakman (Speakman, JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) (-1.9 +/- 2.7%)]. This latter finding seems linked to the stable body mass and to fractionation consideration close to the single-pool model of Speakman. During isolation or simulated microgravity, the other equations underestimated TEE by 10-20%.

Animals↗

Fuel homeostasis during physical inactivity induced by bed rest.

The consequences of physical inactivity on fuel homeostasis were evaluated during 7 days of head-down bed rest (HDBR), a model mimicking weightlessness. Eight men (32.4 +/- 1.9 yr; body mass index, 23.9 +/- 0.7 kg/m2) and eight women (27.9 +/- 0.9 yr; body mass index, 20.9 +/- 0.6 kg/m2) underwent an oral glucose tolerance test (OGTT; 1 g/kg) before and after HDBR. The glucose load was labeled with 13C and associated with D-[6,6-2H2] glucose infusion, indirect calorimetry, breath tests, and plasma measurements to determine the glucose turnover and biodisponibility, substrate oxidation, and endocrine responses. Body composition was assessed using H2(18)O dilution. In addition, hormones were measured in daily blood and 24-h urine samples. No change in body composition was noted. Daily fasting insulin increased during HDBR (men, 34%; women, 26%), as did the insulin to glucose ratio (men, 30%; women, 25%). The normetanephrine level dropped (men, 30%; women, 16%), but metanephrine was unchanged. During OGTTs, the insulin response was increased after HDBR (men, 47%; women, 67%), whereas plasma glucose levels were similar. Nonesterified fatty acids and beta-hydroxybutyrate levels were lower. Endogenous glucose production dropped (28%), and exogenous glucose oxidation increased (28%) only in men. Resting energy expenditure was unchanged, but nonproteic respiratory quotient increased (men, 10%; women, 14%). Basal levels of lipid oxidation dropped in both sexes (approximately 90%), but those of carbohydrate oxidation increased in men (40%); as did lipogenesis in women (570%). In response to OGTTs, lipid oxidation was 80% reduced in both sexes after HDBR, but carbohydrate oxidation increased (25%) in men. Lipogenesis occurred in men (304%) and women (74%), but the latter had higher absolute levels. Therefore, 7 days of HDBR resulted in 1) reduced sympathetic activity, 2) insulin resistance suggested at the muscle level in men and at both the muscle and liver levels in women, 3) no changes in glucose biodisponibility, suggesting no alterations in the gastrointestinal function, and 4) a shift toward carbohydrate oxidation in men and a net lipogenesis in women. Such results suggest gender differences in response to sedentary life style and warrant further analysis.

3-Hydroxybutyric Acid↗

[The effect of age and dehydration on the activity of the vasopressinergic system in rats].

The aim of our work was to study the different blood parameters as well as the activity of the vasopressinergic axis in young and mature male rats under normal conditions and following a 3-day dehydration cycle by water deprivation. Under normal conditions, our study demonstrates higher levels of vasopressin in mature rats as compared to young rats. This could be due in part to the higher blood osmolality in the mature rats. After dehydration, hypovolemia, plasmatic hyperosmolality, hypernatremia and hyperproteinemia cause a stimulation in vasopressin synthesis and release, as seen in results obtained from the hypothalamus, hypophysis and plasma in both young and mature rats. However, the response of the vasopressinergic axis to dehydration is greater in young rats, suggesting a more pronounced sensitivity to osmotic factors.

Aging↗

Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.

BACKGROUND: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Adult↗

Characterization of the central muscarinic cholinoceptors involved in the cholinergic pressor response in anesthetized dogs.

Previous reports have shown that an intracisternal (i.c.) injection of acetylcholine in the dog increases both arterial blood pressure and plasma levels of noradrenaline and vasopressin via central muscarinic receptors. The aim of the present study was to characterize the central muscarinic cholinoceptor subtypes involved in such central cholinergic responses in anesthetized male Beagle-Harrier dogs (n = 12). For this purpose, we studied the relative potency of various muscarinic receptor antagonists to block the acetylcholine-induced pressor responses (30 microg kg(-1) i.c.). The acetylcholine-induced pressor response was inhibited in a dose-dependent manner by the i.c. administration of the non-selective muscarinic receptor antagonist atropine (ID50 = 0.5 microg kg(-1)), the muscarinic M receptor antagonist pirenzepine (ID50 = 0.45 microg kg(-1)), the muscarinic M2 receptor antagonist methoctramine (ID50 = 8.5 microg kg(-1)) and the muscarinic M3 receptor antagonist para-fluoro-hexahydro-sila-difenidol (ID50) = 43.7 microg kg(-1)). The order of potency of these four muscarinic receptor antagonists was: atropine = pirenzepine > methoctramine >> para-fluoro-hexahydro-sila-difenidol. In order to confirm the selectivity for muscarinic M1 receptors of this dose of pirenzepine, we checked that 40- to 50-fold higher concentrations were necessary to block a typical muscarinic M2 receptor response (bradycardia) and a typical muscarinic M3 receptor response (endothelial vasodilation) compared with methoctramine and para-fluoro-hexahydro-sila-difenidol, respectively. These results suggest that the pressor response elicited by intracisternal injection of acetylcholine in anesthetized Beagle-Harrier dogs is mediated through the activation of the muscarinic M1 cholinoceptor subtype.

Acetylcholine↗

Cardiac atrial natriuretic peptide (ANP) in rat dams and fetuses developed in space (NIH-R1 and NIH-R2 experiments).

NIH-R1 and R2 missions, conducted by NASA, allowed us to study the effects of the microgravitational environment 1) on cardiac ANP in pregnant rats, spaceflown for 11 days and dissected after a 2-day readaptation to Earth's gravity, after natural delivery, and 2) on maturation of cardiac ANP system in rat fetuses developed for 11 days in space and dissected on the day of landing, 2 days before birth. Immunocytochemical and electron microscopy analyses showed a typical formation of ANP-containing granules in atrial myocytes, in both dams and fetuses. Using competitive RT-PCR and radioimmunoassays, we observed that, after 2 days of readaptation to Earth's gravity, cardiac ANP biosynthesis of rat dams flown in space was increased by about twice, when compared to Synchronous and Vivarium Control rats. More obviously, rat fetuses developed in space and dissected on the day of landing displayed an altered maturation of cardiac ANP, evidenced by an increased mRNA biosynthesis (by about 6 fold, p<0.05), whereas the cardiac ANP storage was slightly reduced (by about twice, p<0.05) in both Flight and Synchronous Control groups, in comparison with Vivarium Control rats. These last results suggest that ANP metabolism during development is impacted by the microgravitational environment, but also by the housing conditions designed for space flight.

Animals↗

Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat.

We investigated the central and peripheral sympathetic responses to intermittent dehydration in rats. The norepinephrine (NE) turnover, a biochemical index correlated with noradrenergic neuronal activity, was measured. The modification of blood pressure was also determined by telemetry during the different cycles of dehydration. Dehydration caused a decrease of NE turnover in A2, A5 and A6 nuclei and in peripheral organs. The vasopressinergic level of dehydrated rats decreased in hypophysis and hypothalamus, and increased in plasma. A repeated gradual increase of arterial blood pressure during the first three days of dehydration, followed by a sudden drop when the rats were rehydrated on the fourth day was observed. In conclusion, our study revealed an increase in blood pressure and in central sympathetic activity during dehydration.

Animals↗

Effect of a 14-day hindlimb suspension on beta-adrenoreceptors in rats.

Exposure to long-term simulated microgravity exhibits reduced sympathetic nervous system activity. This study tested the hypothesis that the hypersensitivity of adrenoreceptors would explain partly many other features of the hemodynamic consequences of return from space. The biochemical properties of the beta adrenoreceptors (betaAR) were determined using 125I-cyanopindolol (125I-CYP) binding in three rat groups: (1) The first experimental group consisted of 24 h-restrained orthostatic rats in the horizontal position, to test the early effect of the attachment to the suspension device; (2) the second experimental group consisted of 24 h-restrained antiorthostatic rats, to test the early effect of the suspension; (3) the third experimental group consisted of 14 day-restrained antiorthostatic rats, to test the long term effect of the suspension. The study was performed in two organs involved in blood pressure regulation, i.e. the heart (atria and ventricles were separated) and kidneys. The Scatchard analysis of 125I-cyanopindolol binding in both organs indicated no significant alterations in the dissociation constant (Kd) and the maximum binding capacity (Bmax) in the three experimental groups. These results do not allow the conclusion about the SNS adaptation pattern to simulated microgravity. Thus, the hypothesis that betaAR are involved in the cardiovascular adaptation to simulated microgravity is not verified in this model where, as a matter of fact, cardiovascular deconditioning is not verified even if this model is widely used.

Adrenergic beta-Antagonists↗

Effects of acute and chronic starvation on central and peripheral noradrenaline turnover, blood pressure and heart rate in the rat.

When faced with stress, an organism calls upon several mechanisms to maintain biological homeostasis. The cardiovascular system is the first to respond usually with an increase in arterial pressure and tachycardia. Therefore we investigated the central and peripheral sympathetic responses to acute and chronic starvation in Wistar rats. The noradrenaline (NA) turnover rate was determined in different catecholaminergic nuclei (A1, A2, A5, A6) as well as the arterial blood pressure and heart rate modifications. During acute starvation (3 days of starvation), the NA turnover was increased in the A1 and rostral A2 nuclei as well as in ventricles and kidneys and decreased in the A6 nucleus. During chronic starvation (4 consecutive cycles of 3 days of starvation plus 1 day of feeding), the NA turnover was increased in the A5 and caudal A2 nuclei as well as in ventricles and atria and decreased in the A1 nucleus and kidneys. The arterial blood pressure revealed a gradual decrease during the first 3 days of fasting but the heart rate was not modified. We conclude that starvation should be considered as an unusual state of stress because of the absence of locus coeruleus response (A6 nucleus) despite its well-defined role in stress reactions. One of the manifestations of these central and peripheral noradrenergic changes is the change in blood pressure during the starvation-feeding cycles.

Animals↗

Contributory factors to orthostatic intolerance after simulated weightlessness.

Various factors may contribute to orthostatic intolerance (OI) observed after space flights or simulated weightlessness such as bed rest experiments: individual physical and physiological factors (arterial blood pressure (BP), height), physiological changes induced by real or simulated weightlessness (hypovolaemia, increase in venous distensibility), and space flight or simulation conditions (duration and counter-measure application). Our purpose was to test which of these factors were dominant in contributing to the OI. This was assessed in 47 healthy men participating in bed rest experiments of 4, 14, 28, 30 and 42 days, with or without counter-measures (medical stockings, lower-body negative pressure (LBNP), LBNP + muscular exercise). Nineteen subjects did not finish the orthostatic test (60 degrees head-up tilt or stand test) after bed rest. The occurrence of OI was associated with greater height, low resting BP, greater changes in resting lower-limb venous distensibility throughout the bed rest, and absence of counter-measures.

Adult↗

Dietary docosahexaenoic acid-enriched phospholipids normalize urinary melatonin excretion in adult (n-3) polyunsaturated fatty acid-deficient rats.

Melatonin (MEL) plays an essential role in physiologic functions associated with darkness. We examined the effects of docosahexaenoic acid (DHA)-enriched phospholipids from pig brains (BPL) or hen eggs (EPL), as sources of DHA, on lipid FA composition of pineal membranes and daytime and nighttime concentrations of 6-sulfatoxymelatonin (aMT6) in adult male control and (n-3)-deficient rats fed BPL and EPL diets for 5 wk. In two experiments, at 3 wk of age, rats were divided into subgroups and fed semipurified diets containing either peanut oil [(n-3)-deficient group] or peanut plus rapeseed oil (control group) and two dietary formulas containing either 3.5 g/100 g diet of BPL (Experiment 1) or 5.0 g/100 g diet of EPL (Experiment 2). BPL and EPL diets provided approximately 200 mg of DHA/100 g diet. During the daytime, aMT6 concentrations were not significantly different among groups. Conversely, the (n-3)-deficient rats had significantly lower nighttime aMT6 concentrations than the control rats. BPL and EPL did not affect urinary nighttime aMT6 concentration in the control group, whereas (n-3)-deficient + BPL or EPL groups exhibited significantly higher nighttime aMT6 concentrations than the (n-3)-deficient group (76 and 110%, respectively). The level of DHA was significantly higher in the pineal glands of control rats than in (n-3)-deficient rats. In rats fed EPL and BPL, the level of DHA reached a plateau, between 10 and 11 mg/100 mg total fatty acids in control + BPL or EPL and (n-3)-deficient + BPL or EPL groups. These findings suggest that new DHA-enriched formulas may be used as an efficient alternative source of (n-3) polyunsaturated fatty acids to normalize MEL secretion.

Animals↗

Even slight movements disturb analysis of cardiovascular dynamics.

We hypothesized that spontaneous movements (postural adjustments and ideomotion) disturb analysis of heart rate and blood pressure variability and could explain the discrepancy between studies. We measured R-R intervals and systolic blood pressure in nine healthy sitting subjects during three protocols: 1) no movement allowed, 2) movements allowed but not standing, 3) movements and standing allowed. Heart rate and blood pressure were not altered by movements. Movements with or without standing produced a twofold or greater increase of the overall variability of R-R intervals and of the low-frequency components of spectral analysis of heart rate variability. The spectral exponent beta of heart rate variability (1. 123 at rest) was changed by movements (1.364), and the percentage of fractal noise (79% at rest) was increased by standing (91%, coarse-graining spectral analysis). Spontaneous movements could induce a plateau in the correlation dimensions of heart rate variability, but they changed its nonlinear predictability. We suggest that future studies on short-term cardiovascular variability should control spontaneous movements.

Adult↗

Influences of thigh cuffs on the cardiovascular system during 7-day head-down bed rest.

Thigh cuffs, presently named "bracelets," consist of two straps fixed to the upper part of each thigh, applying a pressure of 30 mmHg. The objective was to evaluate the cardiac, arterial, and venous changes in a group of subjects in head-down tilt (HDT) for 7 days by using thigh cuffs during the daytime, and in a control group not using cuffs. The cardiovascular parameters were measured by echography and Doppler. Seven days in HDT reduced stroke volume in both groups (-10%; P < 0.05). Lower limb vascular resistance decreased more in the cuff group than in the control group (-29 vs. -4%; P < 0.05). Cerebral resistance increased in the control group only (+6%; P < 0.05). The jugular vein increased (+45%; P < 0.05) and femoral and popliteal veins decreased in cross-sectional area in both groups (-45 and -8%, respectively; P < 0.05). Carotid diameter tended to decrease (-5%; not significant) in both groups. Heart rate, blood pressure, cardiac output, and total resistance did not change significantly. After 8 h with thigh cuffs, the cardiac and arterial parameters had recovered their pre-HDT level except for blood pressure (+6%; P < 0.05). Jugular vein size decreased from the pre-HDT level (-21%; P < 0.05), and femoral and popliteal vein size increased (+110 and +136%, respectively; P < 0.05). The thigh cuffs had no effect on the development of orthostatic intolerance during the 7 days in HDT.

Adaptation, Physiological↗