Determining an erythropoietin threshold is not sufficient for accelerating erythrocyte production by Julien V. Brugniaux, Aurélien Pichon.
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Biomedical subjects
Publications and source records attributed to Gustave Savourey.
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INTRODUCTION: Residence at high altitude modifies thremoregulatory responses to cold stress upon return to lower altitude. These changes are difficult to explain since several stresses related to high altitude may interact, including hypoxia, cold, solar radiation, and physical exertion. We hypothesized that adaptation to hypoxia without cold exposure would produce at least part of the observed changes. METHODS: Five men underwent acclimation to intermittent hypoxia (AIH) in a hypobaric chamber (8 h daily for 4 d, and 6 h on the last day, 4500 to 6000 m) at 24 degrees C. Cold stress responses were tested during a whole-body standard cold air test (1 degrees C, 2 h at rest at sea level) both before and after AIH. RESULTS: Increased reticulocyte counts and percentages confirmed acclimation to hypoxia after AIH. Changes in thermoregulation during the cold test included lower mean skin temperature after 60-80 min (18.8 +/- 0.7 degrees C vs. 19.4 +/- 0.7 degrees C); higher mean metabolic heat production (127 +/- 8 W x m(-2) vs. 118 +/- 6 W x m(-2)); and lower heat debt (7.7 +/- 1.3 kJ x kg(-1) vs. 10.3 +/- 1.2 kJ x kg(-1)), without significant change in rectal temperature. Time to onset for continuous shivering decreased after AIH (12 +/- 5 min vs. 21 +/- 6.3 min), and shivering activity occurred at higher mean skin but not rectal temperatures. CONCLUSION: AIH in comfortable ambient temperature leads to a normothermic-insulative-metabolic general cold adaptation. We conclude that AIH modifies the thermoregulatory responses to cold at sea level without cold exposure leading to a cross-adaptation.
Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) ( P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content ( C(a)O(2)) (+12.93%) at the end of HH ( P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (-46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only ( r=-0.66, P<0.03). Inverse linear relationships were also found between C(a)O(2) and EPO at the end of HH before ( r=-0.63, P<0.05) and after the sojourn ( r=-0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.
PREDICTOL is a PC program used to determine the thermophysiological duration limited exposures (DLE) in humans, nude or clothed, submitted to various climatic conditions (hot and cold climates) at rest or during a physical exercise. DLE are determined following different standards of the International Standardization Organization (ISO), especially ISO 7933 for hot environment and ISO-TR 11079 for cold environment. The original aspect of this program is that it can be used whatever the climatic conditions. The program presents two modes: an educational interactive mode and a scenario mode. The educational interactive mode demonstrates the thermophysiological effects, expressed as DLE, of different parameter changes (temperature, humidity, wind speed, metabolic heat production by physical exercise, clothing insulation and water vapor permeability). The scenario mode determines DLE for given various linked sequences as encountered in occupational, military or even recreational activities, each sequence being characterized by its climatic conditions, physical activities performed and by physical clothing properties. DLE given by PREDICTOL are correlated to those obtained in various controlled climatic laboratory conditions (r = 0.86; P < 0.001). PREDICTOL is written in Visual Basic 6.0. A "help menu" is provided to explain the use of the program and give information concerning the equations used to calculate both the thermal balance and DLE.
OBJECTIVES: This study evaluates the ability of positive end-expiratory pressure (PEEP), a nonpharmacological method, to prevent the occurrence of acute mountain sickness during two ascents of Mount Blanc. METHODS: In a random order (once with PEEP and once without), PEEP was administered or not to eight subjects during two ascents of Mount Blanc. Scores for acute mountain sickness were quantified using the Lake Louise acute mountain sickness scoring system, and oxygen arterial blood saturation by pulse oxymetry (SpO2), heart rate, and systolic and diastolic blood pressures were also measured. RESULTS: The decrease in the prevalence of acute mountain sickness indicated that the PEEP system was effective, one case (12.5%) occurring among the eight participants with PEEP and six cases (75%) occurring among the eight without PEEP (P<0.01). The severity of the cases also decreased (P<0.01). Heart rate and blood pressure did not significantly vary, whereas the SpO2 tended to be higher with PEEP (P=0.07). CONCLUSIONS: This field study shows that PEEP could be an efficient method with which to prevent acute mountain sickness without adverse effects. However, the ergonomics of the PEEP system must be improved to make its use more practical in the future.
Since Bert (1878) and Barcroft (1925), studies on hypoxia are realized by lowering ambient O(2) partial pressure (PO(2)) either by barometric pressure reduction (hypobaric hypoxia HH) or by lowering the O(2) fraction (normobaric hypoxia NH). Today, a question is still debated: "are there any physiological differences between HH and NH for the same ambient PO(2)?" Since published studies are scarce and controversial, we submitted 18 subjects in a random order to a 40-min HH test and to a 40-min NH test at an ambient PO(2) equal to 120 hPa (4500 m). Cardioventilatory variables [breathing frequency (f), tidal volume (V(t)), minute ventilation (V(E)), O(2) and CO(2) end-tidal fractions or pressures (FET(O2) and FET(CO2) or PET(O2) and PET(CO2) respectively), heart rate (HR) and O(2) arterial saturation by pulse oxymetry (SpO(2))] were measured throughout the tests. At the end of the tests, arterial blood samples were taken to measure arterial blood gases [O(2) and CO(2) arterial partial pressures ( Pa(O2) and Pa(CO2)), pH and O(2) arterial saturation (SaO(2))]. Results show that during HH compared to NH, f is greater (P</=0.001), V(t) and V(E) under BTPS conditions are lower (P</=0.05), and FET(O2) and FET(CO2) are higher (P</=0.05). However, PET(O2) does not change during the last 25 min of the tests, and neither does PET(CO2) throughout the tests. HR is higher (P</=0.05) and SpO(2) lower (P</=0.05) in HH compared to NH. Arterial blood data reveal that hypoxemia, hypocapnia and blood alkalosis are greater in HH compared to NH and that SaO(2) is lower (P</=0.05). It is concluded that the physiological responses of humans submitted to an acute hypoxia at a PO(2) equal to 120 hPa differ according to the type of hypoxia. Compared to NH, HH leads to a greater hypoxemia, hypocapnia, blood alkalosis and a lower O(2) arterial saturation. These physiological differences could be the consequence of an increase in dead space ventilation, probably related to the barometric pressure reduction, and could be grouped together under the term "the specific response to hypobaric hypoxia". Knowledge of this specific response could improve the comprehension, prevention and treatment of altitude illnesses in the future.
PURPOSE: The present study was assessed to study the restoration of the vascular compartment by rehydration after heat exposure or exercise. METHODS: Eight subjects completed four trials in a randomized order: 2.7% dehydration of body mass by passive controlled hyperthermia once with rehydration and once without rehydration during recovery, and 2.7% dehydration of body mass by treadmill exercise once with rehydration and once without rehydration during recovery. An isotonic glucose electrolyte beverage was provided twice during the recovery period for a total volume, which was equivalent to the target value of body mass loss during dehydration procedures. Plasma volume (PV) was measured using Evans Blue dilution technique, and PV changes (deltaPV) were determined using hematocrit and hemoglobin measurements. RESULTS: PV was better maintained during exercise than during heat exposure, and the difference in deltaPV between the two patterns of dehydration was maintained during the first 3 h of recovery. Plasma protein seemed to be accountable for the difference in deltaPV during heat exposure and exercise but not during the 270 min of recovery. Rehydration partly restored body fluid losses, but the plasma compartment was privileged, because 26-30% of the net fluid gain was found in the plasma compartment (about 300 mL). Rehydration restored plasma osmolality and diminished the drive for arginin-vasopressin response. CONCLUSION: The similar selective retention of water in the plasma compartment might essentially be explained by osmotic factors provided by the beverage. As PV was completely restored by rehydration after exercise and only partly restored after heat exposure, the volume of ingested beverage should be higher after heat exposure to completely restore the plasma compartment.
The effects of modafinil on heat thermoregulatory responses were studied in 10 male subjects submitted to a sweating test after taking 200 mg of modafinil or placebo. Sweating tests were performed in a hot climatic chamber (45 degrees C, relative humidity <15%, wind speed = 0.8 m x s(-1), duration 1.5 h). Body temperatures (rectal (Tre) and 10 skin temperatures (Tsk)), sweat rate, and metabolic heat production (M) were studied as well as heart rate (HR). Results showed that modafinil induced at the end of the sweating test higher body temperatures increases (0.50 +/- 0.04 versus 0.24 +/- 0.05 degrees C (P < 0.01) for deltaTre and 3.64 +/- 0.16 versus 3.32 +/- 0.16 degrees C (P < 0.05) for deltaTsk (mean skin temperature)) and a decrease in sweating rate throughout the heat exposure (P < 0.05) without change in M, leading to a higher body heat storage (P < 0.05). AHR was also increased, especially at the end of the sweating test (17.95 +/- 1.49 versus 12.52 +/- 1.24 beats/min (P < 0.01)). In conclusion, modafinil induced a slight hyperthermic effect during passive dry heat exposure related to a lower sweat rate, probably by its action on the central nervous system, and this could impair heat tolerance.
Since human thermoregulation at rest is altered by cold exposure, it was hypothesized that physical training under cold conditions would alter thermoregulation. Three groups (n = 8) of male subjects (mean age 24.3 +/- 0.9 years) were evaluated: group T (interval training at 21 degrees C), group CT (interval training at 1 degrees C), and group C (no training, equivalent exposure to 1 degrees C). Each group was submitted, before and after 4 weeks of interval training (5 d/week), to a cold air test at rest (SCAT) (dry bulb temperature (Tdb) = 1 degrees C) for a 2-h period for evaluation of the thermoregulatory responses. During SCAT, after the training/acclimation period, group T exhibited a higher rectal temperature (Tre) (P < 0.05) without significant change in mean skin temperature (Tsk) whereas metabolic heat production (M) was higher at the beginning of the SCAT (P < 0.05). For group CT, no thermoregulatory change was observed. Group C showed a lower Tre (P < 0.05) without significant change in either Tsk or in M, suggesting the development of a hypothermic general cold adaptation. This study showed, first, that the cold thermoregulatory responses induced by an interval training differed following the climatic conditions of the training and, second, that this training performed in the cold prevented the development of a general cold adaptation.
OBJECTIVE: A survival sojourn in a tropical climate exposes subjects to 2 main constraints: food restriction and tropical climatic conditions. We hypothesized that such a sojourn could modify anthropological characteristics and thermoregulatory responses to heat and cold on return. METHODS: Eight European male subjects were submitted to a sweating test (ST) for 90 minutes (dry bulb temperature [Tdb] = 47 degrees C, relative humidity (RH) = 10%, and wind speed = 0.8 m x s(-1)) and to a whole-body cold-air test (Tdb = 1 degrees C, RH = 40%, and wind speed = 0.8 m x s(-1)) for 120 minutes in thermoclimatic chambers both before and after a 4-week survival sojourn in French Guyana. RESULTS: The survival sojourn resulted in a decrease in lean body mass (P < .05) without any significant change in body fat content. Heat thermoregulatory changes studied during the ST were characterized both by a lower mean skin temperature (Tsk) (P < .05) and a higher sweat rate measured after the sojourn than before it (m(sw); P < .05). Cold thermoregulatory changes were characterized by a higher T(sk) value (P < .05) and a decreased onset for continuous shivering without any significant change in internal temperature or metabolic heat production (M). CONCLUSIONS: This study showed that this type of sojourn modifies not only biometrical characteristics of the subjects but also the thermoregulatory responses, inducing an adaptation of the thermoregulatory system to heat and an increase in the sensitivity of the thermoregulatory system to cold. This finding could have practical implications on return after such a sojourn.
BACKGROUND: Sleep deprivation (SD) induces many adverse psychological and physiological effects, particularly on vigilance and the thermoregulatory system. The drug modafinil appears to suppress or diminish the harmful effects on vigilance. However, the effects of modafinil combined with SD on the circadian rhythm of core temperature are not well established. HYPOTHESIS: We studied the circadian rhythm of rectal temperature (CRTre) during 62 h of SD alone or with three dosage levels of modafinil. METHODS: Six men underwent repeated SD experiments lasting 7 d each, including a 24-h control period, 62 h of SD, and a 24-h recovery period. Experiments were repeated four times in mixed order for placebo and three levels of modafinil (50, 150, or 300 mg x 24 h(-1)). The Tre was recorded each minute throughout the experiment and the CRTre was studied by the single cosinor method. RESULTS: Independent of modafinil, SD increased the mesor (p < 0.05) and reduced the amplitude (p < 0.01) of the CRTre without changing the acrophase. During the recovery period, a rebound increase was seen in the amplitude of the CRTre (p < 0.01). The 50 mg x 24 h(-1) dose of modafinil, but not the higher doses, induced a lower mesor (p < 0.01) independent of SD. CONCLUSIONS: The observed changes may reflect a threshold for the central action of modafinil on core temperature. The hyperthermic effect reported in the literature for SD with modafinil may actually result from the sleep deprivation alone.