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Biomedical subjects

Jean-Paul Richalet

Publications and source records attributed to Jean-Paul Richalet.

At least 19 recordsLinked to original sources
PubMed2006

Living high-training low: effect on erythropoiesis and maximal aerobic performance in elite Nordic skiers.

The "living high-training low" model (Hi-Lo) may improve aerobic performance in athletes, and the main mechanism of this improvement is thought to be augmented erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by using altitudes of 2,000-3,000 m. Since the rate of erythropoiesis is altitude-dependent, we tested whether a higher altitude (3,500 m) during Hi-Lo increases erythropoiesis and maximal aerobic performance. Nordic skiers trained for 18 days at 1,200 m, while sleeping at 1,200 m in ambient air (control group, n = 5) or in hypoxic rooms (Hi-Lo, n = 6; 3 x 6 days at simulated altitudes of 2,500, 3,000 and finally 3,500 m, 11 h day(-1)). Measurements were done before, during (blood samples only) and 2 weeks after the intervention (POST). Maximal aerobic performance was examined from VO(2max) and time to exhaustion (T(exh)) at vVO(2max) (minimum speed associated with VO(2max)), respectively. Erythropoietin and soluble transferrin receptor responses were higher during Hi-Lo, whereas reticulocytes did not change. In POST (vs. before): hematological parameters were similar to basal levels, as well as red blood cell volume, being 2.68 +/- 0.83 l (vs. 2.64+/-0.54 l) in Hi-Lo and 2.62+/-0.57 l (vs. 2.87 +/- 0.59 l) in controls. At that time, neither VO(2max) nor T(exh) were improved by Hi-Lo, VO(2max) being non-significantly decreased by 2.0% (controls) and 3.7% (Hi-Lo). The present results suggest that increasing the altitude up to 3,500 m during Hi-Lo stimulates erythropoiesis but does not confer any advantage for maximal O2 transport.

Adult↗
PubMed2006

Influence of "living high-training low" on aerobic performance and economy of work in elite athletes.

This study tested the effects of "living high-training low" (Hi-Lo) on aerobic performance and economy of work in elite athletes. Forty endurance athletes (cross-country skiers, swimmers, runners) performed 13-18 consecutive days of training at 1,200 m altitude, by sleeping at 1,200 m (LL, n = 20) or in hypoxic rooms with 5-6 nights at 2,500 m followed by 8-12 nights at 3,000-3,500 m (HL, n = 20). The athletes were evaluated before (pre-), one (post-1) and 15 days (post-15) after Hi-Lo. Economy was assessed from two sub-maximal tests, one non-specific (cycling) and one specific (running or swimming). From pre- to post-1: V(O2)max increased both in HL (+ 7.8%, P < 0.01) and in LL (+ 3.3%, P < 0.05), peak power output (PPO) tended to increase more (P=0.06) in HL (+ 4.1%, P < 0.01) than in LL (+ 1.9%). At post-15, V(O2)max has returned to pre-values in both groups, PPO increased more (P < 0.05) in HL (+ 8.3%, P < 0.01) than in LL (+ 3.8%), V(O2) and power at respiratory compensation point (RCP) increased more (P < 0.05) in HL (+ 9.5%, P < 0.01 and + 11.2%, P < 0.01) than in LL (+ 3.2 and + 3.3%). Cycling mechanical efficiency (8-5%) and economy during specific locomotion (7-7%) increased (P < 0.05) in both groups. This study shows that, for a similar increase in V(O2)max HL had a greater increase in PPO than LL. The efficiency of Hi-Lo is also evidenced 15 days later by higher V(O2) and power at RCP. This study emphasizes that during the post-altitude period, economy of work greatly increases in both groups.

Acclimatization↗
PubMed2006

Respiratory control in residents at high altitude: physiology and pathophysiology.

Highland population (HA) from the Andes, living above 3000 m, have a blunted ventilatory response to increasing hypoxia, breathe less compared to acclimatized newcomers, but more, compared to sea-level natives at sea level. Subjects with chronic mountain sickness (CMS) breathe like sea-level natives and have excessive erythrocytosis (EE). The respiratory stimulation that arises through the peripheral chemoreflex is modestly less in the CMS group when compared with the HA group at the same P(ET(O2)). With regard to CO(2) sensitivity, CMS subjects seem to have reset their central CO(2) chemoreceptors to operate around the sea-level resting P(ET(CO2)). Acetazolamide, an acidifying drug that increases the chemosensitivity of regions in the brain stem that contain CO(2)/H(+) sensitive neurons, partially reverses this phenomenon, thus, providing CMS subjects with the possibility to have high CO(2) changes, despite small changes in ventilation. However, the same type of adjustments of the breathing pattern established for Andeans has not been found necessarily in Asian humans and/or domestic animals nor in the various high altitude species studied. The differing time frames of exposure to hypoxia among the populations, as well as the reversibility of the different components of the respiratory process at sea level, provide key concepts concerning the importance of time at high altitude in the evolution of an appropriate breathing pattern.

Acclimatization↗
PubMed2006

Leukocyte's Hif-1 expression and training-induced erythropoietic response in swimmers.

PURPOSE: Altitude training is popular among athletes to augment oxygen delivery capabilities to tissues and to improve physical performance. Hypoxia inducible factor-1 (HIF-1) controls the expression of several genes' encoding involved in physiological responses towards reduced oxygen availability, in particular by increasing serum erythropoietin (EPO). It may be involved in the individual variability for erythropoietic markers and/or sea-level performance of athletes using altitude during their training. Therefore, we investigated whether, before training, evolutions of hif-1alpha and ahif (HIF-1alpha natural antisense) transcript amounts and HIF-1alpha protein quantities in leukocytes measured during an acute hypoxia normobaric test (3 h at 3000 m at rest) could allow to predict poor and good responders for hematological markers after a "living high-training low" protocol. METHODS: Eighteen elite swimmers were divided into two groups that followed a 13-d training program: "living low-training low" (1200 m) (LL) or "living high (2500-3000 m)-training low (1200 m)" (LH). RESULTS: During the initial hypoxia test, a strong interindividual variability in the amounts of HIF-1alpha mRNA, aHIF transcript, and HIF-1alpha protein was observed in athlete leukocytes (after vs before): -82%/+396%, -100%/+229%, and -100%/+633%, respectively. After the test, serum erythropoietin concentration was increased (11.2 +/- 0.8 vs 9.8 +/- 0.8 IU.L(-1); +18%, P = 0.01). After the training protocol, total red cell volume (+7.6%, P = 0.04) and circulating hemoglobin amount (48.8 +/- 2.8 vs 45.5 +/- 3.0 mmol; i.e., +7.9%, P = 0.02) were significantly augmented in LH. CONCLUSION: We conclude that hif-1alpha gene expression quantification in leukocytes after a 3-h hypoxia test performed before training does not predict poor and good responder athletes to "living high-training low" model.

Altitude↗
PubMed2005

Living high-training low: effect on erythropoiesis and aerobic performance in highly-trained swimmers.

The "living high-training low" model (LHTL), i.e., training in normoxia but sleeping/living in hypoxia, is designed to improve the athletes performance. However, LHTL efficacy still remains controversial and also little is known about the duration of its potential benefit. This study tested whether LHTL enhances aerobic performance in athletes, and if any positive effect may last for up to 2 weeks after LHTL intervention. Eighteen swimmers trained for 13 days at 1,200 m while sleeping/living at 1,200 m in ambient air (control, n=9) or in hypoxic rooms (LHTL, n=9, 5 days at simulated altitude of 2,500 m followed by 8 days at simulated altitude of 3,000 m, 16 h day(-1)). Measures were done before 1-2 days (POST-1) and 2 weeks after intervention (POST-15). Aerobic performance was assessed from two swimming trials, exploring .VO(2max) and endurance performance (2,000-m time trial), respectively. Reticulocyte, serum EPO and soluble transferrin receptor responses were not altered by LHTL, whereas reticulocytes decreased in controls. In POST-1 (vs. before): red blood cell volume increased in LHTL only (+8.5%, P=0.03), .VO(2max) tended to increase more in LHTL (+8.1%, P=0.09) than in controls (+2.5%, P=0.21) without any difference between groups (P=0.42) and 2,000-m performance was unchanged with LHTL. In POST-15, both performance and hematological parameters were similar to initial levels. Our results indicate that LHTL may stimulate red cell production, without any concurrent amelioration of aerobic performance. The absence of any prolonged benefit after LHTL suggests that this LHTL model cannot be recommended for long-term purposes.

Altitude↗
PubMed2005

Interactions between exposure to hypoxia and the training-induced autonomic adaptations in a "live high-train low" session.

The autonomic and cardiovascular adaptations to hypoxia are opposite to those resulting from aerobic training. We investigated (1) whether exposure to hypoxia in a live high-train low (LHTL) session limits the autonomic and cardiovascular adaptations to training, and (2) whether such interactions remain 15 days after the end of the LHTL. Eighteen national swimmers trained for 13 days at 1,200 m, living (16 h day(-1)) either at 1,200 m (live low-train low, LLTL) or at a simulated height of 2,500-3,000 m (LHTL). Subjects were investigated at 1,200 m before and at the end of the training session, and after the following 15 days of sea-level training. Cardiovascular parameters and the autonomic control assessed by spectral analysis of R-R and diastolic blood pressure (DBP) variability were obtained in the resting supine position and in response to an orthostatic test. At the end of the 13-day training, resting heart rate (HR) and sympathetic modulation on heart decreased in LLTL (-10.1% and -25.4%, P<0.01, respectively) but not in LHTL (-5.8, -15.5%, respectively). Total peripheral resistance (TPR) and DBP became higher in LHTL than in LLTL (P<0.05). Stroke index decreased in both groups during the tilt test, counteracted by an increase in HR and sympathetic modulation to the heart and vasculature, and a decrease in vagal modulation to the heart. After the following 15-day sea-level training, differences in TPR and DBP between groups disappeared. During an LHTL session, adaptations to hypoxia interacted with the autonomic and cardiovascular adaptations to training. However, these interactions did not limit the adaptations to the following sea-level training.

Adaptation, Physiological↗
PubMed2005

Living high-training low: tolerance and acclimatization in elite endurance athletes.

The "living high-training low" (LHTL) model is frequently used to enhance aerobic performance. However, the clinical tolerance and acclimatization process to this intermittent exposure needs to be examined. Forty one athletes from three federations (cross-country skiers, n=11; swimmers, n=18; runners, n=12) separately performed a 13 to 18-day training at the altitude of 1,200 m, by sleeping either at 1,200 m (CON) or in hypoxic rooms (HYP), with an O2 fraction corresponding to 2,500 m (5 nights for swimmers and 6 for skiers and runners), 3,000 m (6 nights for skiers, 8 for swimmers and 12 for runners) and 3,500 m (6 nights for skiers). Measurements performed before, 1 or 15 days after training were ventilatory response (HVRe) and desaturation (deltaSaO2e) during hypoxic exercise, an evaluation of cardiac function by echocardiography, and leukocyte count. Lake Louise AMS score and arterial O2 saturation during sleep were measured daily for HYP. Subjects did not develop symptoms of AMS. Mean nocturnal SaO2 decreased with altitude down to 90% at 3,500 m and increased with acclimatization (except at 3,500 m). Leukocyte count was not affected except at 3,500 m. The heart function was not affected by LHTL. Signs of ventilatory acclimatization were present immediately after training (increased HVRe and decreased deltaSaO2e) and had disappeared 15 days later. In conclusion, LHTL was well tolerated and compatible with aerobic training. Comparison of the three patterns of training suggests that a LHTL session should not exceed 3,000 m, for at least 18 days, with a minimum of 12 h day(-1) of exposure.

Acclimatization↗
PubMed2005

Exercise training improves lung gas exchange and attenuates acute hypoxic pulmonary hypertension but does not prevent pulmonary hypertension of prolonged hypoxia.

Our laboratory has previously shown an attenuation of hypoxic pulmonary hypertension by exercise training (ET) (Henderson KK, Clancy RL, and Gonzalez NC. J Appl Physiol 90: 2057-2062, 2001), although the mechanism was not determined. The present study examined the effect of ET on the pulmonary arterial pressure (Pap) response of rats to short- and long-term hypoxia. After 3 wk of treadmill training, male rats were divided into two groups: one (HT) was placed in hypobaric hypoxia (380 Torr); the second remained in normoxia (NT). Both groups continued to train in normoxia for 10 days, after which they were studied at rest and during hypoxic and normoxic exercise. Sedentary normoxic (NS) and hypoxic (HS) littermates were exposed to the same environments as their trained counterparts. Resting and exercise hypoxic arterial P(O2) were higher in NT and HT than in NS and HS, respectively, although alveolar ventilation of trained rats was not higher. Lower alveolar-arterial P(O2) difference and higher effective lung diffusing capacity for O2 in NT vs. NS and in HT vs. HS suggest ET improved efficacy of gas exchange. Pap and Pap/cardiac output were lower in NT than NS in hypoxia, indicating that ET attenuates the initial vasoconstriction of hypoxia. However, ET had no effect on chronic hypoxic pulmonary hypertension: Pap and Pap/cardiac output in hypoxia were similar in HS vs HT. However, right ventricular weight was lower in HT than in HS, although Pap was not different. Because ET attenuates the initial pulmonary vasoconstriction of hypoxia, development of pulmonary hypertension may be delayed in HT rats, and the time during which right ventricular afterload is elevated may be shorter in this group. ET effects may improve the response to acute hypoxia by increasing efficacy of gas exchange and lowering right ventricular work.

Acute Disease↗
PubMed2005

Eighteen days of "living high, training low" stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners.

The efficiency of "living high, training low" (LHTL) remains controversial, despite its wide utilization. This study aimed to verify whether maximal and/or submaximal aerobic performance were modified by LHTL and whether these effects persist for 15 days after returning to normoxia. Last, we tried to elucidate whether the mechanisms involved were only related to changes in oxygen-carrying capacity. Eleven elite middle-distance runners were tested before (Pre), at the end (Post1), and 15 days after the end (Post2) of an 18-day LHTL session. Hypoxic group (LHTL, n = 5) spent 14 h/day in hypoxia (6 nights at 2,500 m and 12 nights at 3,000 m), whereas the control group (CON, n = 6) slept in normoxia (1,200 m). Both LHTL and CON trained at 1,200 m. Maximal oxygen uptake and maximal aerobic power were improved at Post1 and Post2 for LHTL only (+7.1 and +3.4% for maximal oxygen uptake, +8.4 and +4.7% for maximal aerobic power, respectively). Similarly oxygen uptake and ventilation at ventilatory threshold increased in LHTL only (+18.1 and +12.2% at Post1, +15.9 and +15.4% at Post2, respectively). Heart rate during a 10-min run at 19.5 km/h decreased for LHTL at Post2 (-4.4%). Despite the stimulation of erythropoiesis in LHTL shown by the 27.4% increase in serum transferrin receptor and the 10.1% increase in total hemoglobin mass, red cell volume was not significantly increased at Post1 (+9.2%, not significant). Therefore, both maximal and submaximal aerobic performance in elite runners were increased by LHTL mainly linked to an improvement in oxygen transport in early return to normoxia and probably to other process at Post2.

Adaptation, Physiological↗
PubMed2005

Simulated high altitude selectively decreases protein intake and lean mass gain in rats.

The aim of this study was to find out whether high altitude (HA)-induced hypophagia was macronutrient-specific using a self-selection procedure. Body composition was assessed by dual X-ray absorptiometry before and after exposure and by dissection at the end of the experiment. Energy intake, macronutrient selection, body composition, plasma insulin and leptin concentrations were measured in rats (FHx) exposed 16 h daily for 10 days to hypobaric hypoxia (HH) simulating an altitude of 5500 m. Rats were fasted during the exposure to HH and had access to food only during the 8 h of normoxia in their active period. This group was compared to control group (C) with ad libitum access to food and a group of rats submitted only to the 16-h fast (FNx). Results showed that sustained hypophagia was specific to protein (55 +/- 5% of C, P < .05), whereas after a decline, carbohydrate intake reached its basal level on the 5th day. HH dramatically reduced fat-free mass gain (P < .05 and P < .0001 compared to C and FNx, respectively). Plasma leptin concentrations at the onset of the period of access to food were not significantly different from those of controls. Across groups, leptin was positively correlated with fat mass (r = .71, P < .001) and negatively with energy intake (r = -.52, P < .05), more specifically with protein intake (r = -.57, P < .05). These results suggest that HA leads to a reduced preference for protein impairing fat-free mass gain and that leptin may contribute to this hypophagia.

Altitude↗
PubMed2005

Acetazolamide: a treatment for chronic mountain sickness.

RATIONALE: Chronic mountain sickness or Monge's disease is characterized by an excessive polycythemia in high-altitude dwellers, with a prevalence of 5 to 18% above 3,200 m. To date, no pharmacologic treatment is available. OBJECTIVES: We evaluated the efficacy of acetazolamide in the treatment of chronic mountain sickness and the importance of nocturnal hypoxemia in its pathophysiology. METHODS: A double-blind placebo-controlled study was performed in three groups of patients from Cerro de Pasco, Peru (4,300 m), treated orally for 3 weeks with placebo (n = 10), 250 mg of acetazolamide (n = 10), or 500 mg of acetazolamide (n = 10), daily. RESULTS: Acetazolamide decreased hematocrit by 7.1% (p < 0.001) and 6.7% (p < 0.001), serum erythropoietin by 67% (p < 0.01) and 50% (p < 0.001), and serum soluble transferrin receptors by 11.1% (p < 0.05) and 3.4% (p < 0.001), and increased serum ferritin by 540% (p < 0.001) and 134% (p < 0.001), for groups treated with 250 and 500 mg of acetazolamide, respectively. Acetazolamide (250 mg) increased nocturnal arterial O(2) saturation by 5% (p < 0.01) and decreased mean nocturnal heart rate by 11% (p < 0.05) and the number of apnea-hypopnea episodes during sleep by 74% (p < 0.05). The decrease in erythropoietin was attributed mainly to the acetazolamide-induced increase in ventilation and arterial O(2) saturation. CONCLUSIONS: Acetazolamide, the first efficient pharmacologic treatment of chronic mountain sickness without adverse effects, reduces hypoventilation, which may be accentuated during sleep, and blunts erythropoiesis. Its low cost may allow wide development with a considerable positive impact on public health in high-altitude regions.

Acetazolamide↗
PubMed2005

Consensus statement on chronic and subacute high altitude diseases.

This is an international consensus statement of an ad hoc committee formed by the International Society for Mountain Medicine (ISMM) at the VI World Congress on Mountain Medicine and High Altitude Physiology (Xining, China; 2004) and represents the committee's interpretation of the current knowledge with regard to the most common chronic and subacute high altitude diseases. It has been developed by medical and scientific authorities from the committee experienced in the recognition and prevention of high altitude diseases and is based mainly on published, peer-reviewed articles. It is intended to include all legitimate criteria for choosing to use a specific method or procedure to diagnose or manage high altitude diseases. However, the ISMM recognizes that specific patient care decisions depend on the different geographic circumstances involved in the development of each chronic high altitude disease. These guidelines are established to inform the medical services on site who are directed to solve high altitude health problems about the definition, diagnosis, treatment, and prevention of the most common chronic high altitude diseases. The health problems associated with life at high altitude are well documented, but health policies and procedures often do not reflect current state-of-the-art knowledge. Most of the cases of high altitude diseases are preventable if on-site personnel identify the condition and implement appropriate care.

Acclimatization↗
PubMed2005

Effects of intermittent hypoxia on heart rate variability during rest and exercise.

Changes in heart rate variability induced by an intermittent exposure to hypoxia were evaluated in athletes unacclimatized to altitude. Twenty national elite athletes trained for 13 days at 1200 m and either lived and slept at 1200 m (live low, train low, LLTL) or between 2500 and 3000 m (live high, train low, LHTL). Subjects were investigated at 1200 m prior to and at the end of the 13-day training camp. Exposure to acute hypoxia (11.5% O(2)) during exercise resulted in a significant decrease in spectral components of heart rate variability in comparison with exercise in normoxia: total power (p < 0.001), low-frequency component. LF (p < 0.001), high-frequency component, HF (p < 0.05). Following acclimatization, the LHTL group increased its LF component (p < 0.01) and LF/HF ratio during exercise in hypoxia after the training period. In parallel, exposure to intermittent hypoxia caused an increased ventilatory response to hypoxia. Acclimatization modified the correlation between the ventilatory response to hypoxia at rest and the difference in total power between normoxia and hypoxia (r (2) = 0.65, p < 0.001). The increase in total power, LF component, and LF/HF ratio suggests that intermittent hypoxic training increased the response of the autonomic nervous system mainly through increased sympathetic activity.

Acclimatization↗
PubMed2005

Effect of acute hypoxia on maximal exercise in trained and sedentary women.

PURPOSE: The purpose of this study was to determine the physiological responses of sedentary and endurance-trained female subjects during maximal exercise at different levels of acute hypoxia. METHODS: Fourteen women who were sea level residents were divided into two groups according to their level of fitness: 1) endurance-trained women (TW) (N = 7), VO(2max) = 56.3 +/- 4.7 mL.kg(-1).min(-1); and 2) sedentary women (SW) (N = 7), VO(2max) = 34.8 +/- 5.6 mL.kg(-1).min(-1). Subjects performed four maximal cycle ergometer tests in normoxia and under hypoxic conditions (F(I)O(2) = 0.187, 0.154, and 0.117, corresponding to altitudes of 1000, 2500, and 4500 m, respectively). RESULTS: VO(2max) decreased significantly by 3.6 +/- 2.1, 14 +/- 2.5, and 27.4 +/- 3.6% in TW, and by 5 +/- 4, 9.4 +/- 6.4, and 18.7 +/- 7% in SW at 1000, 2500, and 4500 m, respectively. The drop of VO(2max) (DeltaVO(2max)) was greater in TW at and above 2500 m. Arterial O2 saturation (SpO(2)) at maximal exercise was lower in TW at every altitude (1000 m: 90.9 +/- 1.9 vs 94.6 +/- 1.4%; 2500 m: 82.8 +/- 2.8 vs 90.0 +/- 2.1%; 4500 m: 65.0 +/- 4.7 vs 73.6 +/- 4.5%). Maximal heart rate decreased significantly from 1000 m in the two groups. SpO(2) was correlated to DeltaVO(2max) at 4500 m (r = -0.81, P < 0.01) and 2500 m (r = -0.81, P < 0.01), but not below. Furthermore, we noted a relationship between SpO(2) and O2 pulse (VO(2)/HR) at every F(I)O(2). CONCLUSION: These results demonstrate that endurance-trained women show a greater decrement in VO(2max) at high altitudes. This could be explained mainly by a higher arterial desaturation, which is largely caused, according to our results, by diffusion limitation.

Adult↗
PubMed2005

Autonomic adaptations in andean trained participants to a 4220-m altitude marathon.

PURPOSE: Both training and chronic hypoxia act on the autonomic nervous system. Because trained Andean high-altitude natives could perform a high-altitude marathon (4220 m above sea level) in 02:27:23 h, we hypothesized that living in chronic hypoxia does not limit the training-induced benefits on the autonomic modulation of the heart. METHODS: Trained (N=13) and sedentary (N=11) Andean high-altitude natives performed an active orthostatic test. Eight of the trained subjects repeated the test 6-8 and 20-24 h after the end of a high-altitude marathon. Resting heart rate (HR) and the autonomic modulation of the heart were assessed by time domain and spectral analysis of HR variability (HRV): sympathetic (RR low frequency (LF)) and parasympathetic (RR high frequency (HF)) modulations, and sympathovagal balance (RR-LF:HF ratio). RESULTS: Trained subjects exhibited a higher total power of HRV and a lower resting HR (+30%, P<0.005) than sedentary subjects secondary to a higher and dominant parasympathetic modulation on sympathetic activity (RR-HF, RR-LF:HF ratio). At 6-8 h after the marathon, total power of HRV decreased (-69%), whereas resting HR increased from basal level (+22%), mainly because of a rise in sympathetic modulation (RR-LF, RR-LF:HF ratio). From 8 to 24 h of recovery, sympathetic modulation fell (RR-LF, RR-LF:HF ratio) and all HRV parameters were restored. Responses to the active standing position did not change between each recording session. CONCLUSION: Living in chronic hypoxia does not limit the training-induced benefits on the autonomic control of the cardiovascular system in Andean high-altitude natives. The sympathetic predominance on the heart observed 6-8 h after the high-altitude marathon disappeared after 1 d of recovery. Therefore, living at high altitude does not impair the autonomic response to training.

Adaptation, Physiological↗
PubMed2004

Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension.

Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Autonomic control of the cardiovascular system during acclimatization to high altitude: effects of sildenafil.

Both acute hypoxia and sildenafil may influence autonomic control through transient cardiovascular effects. In a double-blind study, we investigated whether sildenalfil (Sil) could interfere with cardiovascular effects of hypoxia. Twelve healthy men [placebo (Pla) n = 6; Sil, n = 6] were exposed to an altitude of 4,350 m during 6 days. Treatment was continuously administered from 6 to 8 h after arrival at altitude (3 x 40 mg/day). The autonomic control on the heart was assessed by heart rate variability (HRV) during sleep at sea level (SL) and between day 1-2 and day 5-6 in hypoxia. Arterial pressure (AP) and total peripheral resistances (TPR) were obtained during daytime. There was no statistical difference between groups in HRV, AP, and TPR throughout the study. Hypoxia induced a decrease in R-R interval and an increase in AP in both groups. Low frequency-to-high frequency ratio increased at day 1-2 (Pla, P = 0.04; Sil, P = 0.02) and day 5-6 (Pla and Sil, P = 0.04) vs. SL, whereas normalized high-frequency power decreased only in Pla (P = 0.04, day 1-2 vs. SL). Normalized low-frequency power increased at high altitude (Pla and Sil, P = 0.04, day 5-6 vs. SL). TPR decreased at day 2 in Pla (P = 0.02) and tended to normalize at day 6 (P = 0.07, day 6 vs. day 2). Acute hypoxia induced a decrease in parasympathetic and increase in sympathetic tone, which tended to be reversed with acclimatization. Sil had no deleterious effects on the cardiovascular response to high-altitude exposure and its control by the autonomic nervous system.

Acclimatization↗