Subudhi AW, Lorenz MC, Fulco CS, Roach RC. Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance. Am J Physiol Heart Circ Physiol 294: H164-H171, 2008. First published November 21, 2007 doi:10.1152/ajpheart.01104.2007.-We sought to describe cerebrovascular responses to incremental exercise and test the hypothesis that changes in cerebral oxygenation influence maximal performance. Eleven men cycled in three conditions: 1) sea level (SL); 2) acute hypoxia [AH; hypobaric chamber, inspired PO2 (PIO 2 ) 86 Torr]; and 3) chronic hypoxia [CH; 4,300 m, PIO 2 86 Torr]. At maximal work rate (Ẇ max), fraction of inspired oxygen (FIO 2 ) was surreptitiously increased to 0.60, while subjects were encouraged to continue pedaling. Changes in cerebral (frontal lobe) (COX) and muscle (vastus lateralis) oxygenation (MOX) (near infrared spectroscopy), middle cerebral artery blood flow velocity (MCA Vmean; transcranial Doppler), and end-tidal PCO2 (PETCO 2 ) were analyzed across %Ẇ max (significance at P Ͻ 0.05). At SL, PETCO 2 , MCA Vmean, and COX fell as work rate rose from 75 to 100% Ẇ max. During AH, PETCO 2 and MCA Vmean declined from 50 to 100% Ẇ max, while COX fell from rest. With CH, PETCO 2 and COX dropped throughout exercise, while MCA Vmean fell only from 75 to 100% Ẇ max. MOX fell from rest to 75% Ẇ max at SL and AH and throughout exercise in CH. The magnitude of fall in COX, but not MOX, was different between conditions (CH Ͼ AH Ͼ SL). FIO 2 0.60 at Ẇ max did not prolong exercise at SL, yet allowed subjects to continue for 96 Ϯ 61 s in AH and 162 Ϯ 90 s in CH. During FIO 2 0.60, COX rose and MOX remained constant as work rate increased. Thus cerebral hypoxia appeared to impose a limit to maximal exercise during hypobaric hypoxia (PIO 2 86 Torr), since its reversal was associated with improved performance. altitude; near infrared spectroscopy; cerebral blood flow; fatigue; muscle oxygenation CEREBRAL HYPOXIA HAS BEEN proposed to be a critical factor limiting exercise performance (37), particularly in hypoxia (7), yet little evidence exists to directly support this theory. Kayser et al. (31) were the first to show that rapidly increasing the fraction of inspired oxygen (FI O 2 ) at the point of maximal exertion prolonged exercise in hypoxia-acclimatized subjects. They concluded that the effect of increased FI O 2 was too quick to have reversed metabolic factors associated with peripheral (intramuscular) fatigue and suggested that cerebral reoxygenation was a more likely explanation for the improvement in exercise performance. Calbet et al. (11) arrived at similar conclusions after using a comparable model to study factors limiting O 2 uptake (V O 2 ). They suggested that exercise under hypoxic conditions may have presented a significant threat to cerebral oxygenation; thus cardiac and/or motor output was curtailed to maintain favorable tissue oxygenation status.While these studies insinuate the importance of preserving cerebral oxygenation during exer...

Progressive body weight loss occurs during high mountain expeditions, but whether it is due to hypoxia, inadequate diet, malabsorption, or the multiple stresses of the harsh environment is unknown. To determine whether hypoxia due to decompression causes weight loss, six men, provided with a palatable ad libitum diet, were studied during progressive decompression to 240 Torr over 40 days in a hypobaric chamber where hypoxia was the major environmental variable. Caloric intake decreased 43.0% from 3,136 to 1,789 kcal/day (P less than 0.001). The percent carbohydrate in the diet decreased from 62.1 to 53.2% (P less than 0.001). Over the 40 days of the study the subjects lost 7.4 +/- 2.2 (SD) kg and 1.6% (2.5 kg) of the total body weight as fat. Computerized tomographic scans indicated that most of the weight loss was derived from fat-free weight. The data indicated that prolonged exposure to the increasing hypoxia was associated with a reduction in carbohydrate preference and body weight despite access to ample varieties and quantities of food. This study suggested that hypoxia can be sufficient cause for the weight loss and decreased food consumption reported by mountain expeditions at high altitude.

In previous gender comparisons of muscle performance, men and women rarely have been closely matched, absolute force has not been equalized, and rates of fatigue and early recovery have not been determined. We compared adductor pollicis muscle performance at a similar absolute force development in healthy men and women (both n=9) matched for adductor pollicis maximal voluntary contraction (MVC) force (132 +/- 5 N for women and 136 +/- 4 N for men, mean +/- SE, P > 0.05). Subjects repeated static contractions at a target force of approximately 50% of MVC force of rested muscle (68 +/- 3 N or 51.9 +/- 1.0% MVC for women and 72 +/- 2 N or 53.0 +/- 2.0% MVC for men, P > 0.05) for 5 s followed by 5 s rest until exhaustion, i. e. inability to maintain the target force for 5 s. MVC force was measured following each minute of exercise, at exhaustion, and after each minute for 3 min of passive recovery. For women compared with men: MVC force fell less after 1 min of exercise (to 93 +/- 1% vs. 80 +/- 3% of MVC force of rested muscle, respectively, P < 0.05); MVC force (N min-1) fell approximately 2-fold slower (P < 0.05); and endurance time to exhaustion was nearly two times longer (14.7 +/- 1. 6 min vs. 7.9 +/- 0.7 min, P < 0.05). After declining to a similar level of MVC force of rested muscle at exhaustion (56 +/- 1% for women and 56 +/- 3% for men), MVC force rose faster in women than in men (to 71 +/- 2% vs. 65 +/- 3% of MVC force of rested muscle, respectively; P < 0.05) during the first minute of recovery. The findings are consistent with the hypothesis that slower adductor pollicis muscle fatigue in women is linked with differences between men and women both in impairment of force generating capacity, per se, and in rates of recovery between contractions.

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

Using an exercise device that integrates maximal voluntary static contraction (MVC) of knee extensor muscles with dynamic knee extension, we compared progressive muscle fatigue, i.e., rate of decline in force-generating capacity, in normoxia (758 Torr) and hypobaric hypoxia (464 Torr). Eight healthy men performed exhaustive constant work rate knee extension (21 +/- 3 W, 79 +/- 2 and 87 +/- 2% of 1-leg knee extension O2 peak uptake for normoxia and hypobaria, respectively) from knee angles of 90-150 degrees at a rate of 1 Hz. MVC (90 degrees knee angle) was performed before dynamic exercise and during < or = 5-s pauses every 2 min of dynamic exercise. MVC force was 578 +/- 29 N in normoxia and 569 +/- 29 N in hypobaria before exercise and fell, at exhaustion, to similar levels (265 +/- 10 and 284 +/- 20 N for normoxia and hypobaria, respectively; P > 0.05) that were higher (P < 0.01) than peak force of constant work rate knee extension (98 +/- 10 N, 18 +/- 3% of MVC). Time to exhaustion was 56% shorter for hypobaria than for normoxia (19 +/- 5 vs. 43 +/- 7 min, respectively; P < 0.01), and rate of right leg MVC fall was nearly twofold greater for hypobaria than for normoxia (mean slope = -22.3 vs. -11.9 N/min, respectively; P < 0.05). With increasing duration of dynamic exercise for normoxia and hypobaria, integrated electromyographic activity during MVC fell progressively with MVC force, implying attenuated maximal muscle excitation. Exhaustion, per se, was postulated to related more closely to impaired shortening velocity than to failure of force-generating capacity.

We hypothesized that progesterone-mediated ventilatory stimulation during the midluteal phase of the menstrual cycle would increase exercise minute ventilation (VE; l/min) at sea level (SL) and with acute altitude (AA) exposure but would only increase arterial O2 saturation (SaO2, %) with AA exposure. We further hypothesized that an increased exercise SaO2 with AA exposure would enhance O2 transport and improve both peak O2 uptake (VO2 peak; ml x kg-1 x min-1) and submaximal exercise time to exhaustion (Exh; min) in the midluteal phase. Eight female lowlanders [33 +/- 3 (mean +/- SD) yr, 58 +/- 6 kg] completed a VO2 peak and Exh test at 70% of their altitude-specific VO2 peak at SL and with AA exposure to 4,300 m in a hypobaric chamber (446 mmHg) in their early follicular and midluteal phases. Progesterone levels increased (P < 0.05) approximately 20-fold from the early follicular to midluteal phase at SL and AA. Peak VE (101 +/- 17) and submaximal VE (55 +/- 9) were not affected by cycle phase or altitude. Submaximal SaO2 did not differ between cycle phases at SL, but it was 3% higher during the midluteal phase with AA exposure. Neither VO2 peak nor Exh time was affected by cycle phase at SL or AA. We conclude that, despite significantly increased progesterone levels in the midluteal phase, exercise VE is not increased at SL or AA. Moreover, neither maximal nor submaximal exercise performance is affected by menstrual cycle phase at SL or AA.

Acute mountain sickness (AMS) commonly occurs at altitudes exceeding 2000-2500 m and usually resolves after acclimatization induced by a few days of chronic residence at the same altitude. Increased ventilation and diuresis may contribute to the reduction in AMS with altitude acclimatization. The aim of the present study was to examine the effects of intermittent altitude exposures (IAE), in combination with rest and exercise training, on the incidence and severity of AMS, resting ventilation and 24-h urine volume at 4300 m. Six lowlanders (age, 23 +/- 2 years; body weight, 77 +/- 6 kg; values are means +/- S.E.M.) completed an Environmental Symptoms Questionnaire (ESQ) and Lake Louise AMS Scoring System (LLS), a resting end-tidal partial pressure of CO2 ( PETCO2) test and a 24-h urine volume collection at sea level (SL) and during a 30 h exposure to 4300 m altitude-equivalent (barometric pressure=446 mmHg) once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h.day(-1), 5 days.week(-1), 4300 m). The previously validated factor score, AMS cerebral score, was calculated from the ESQ and the self-report score was calculated from the LLS at 24 h of altitude exposure to assess the incidence and severity of AMS. During each IAE, three subjects cycled for 45-60 min.day(-1) at 60-70% of maximal O2 uptake (VO2 max) and three subjects rested. Cycle training during each IAE did not affect any of the measured variables, so data from all six subjects were combined. The results showed that the incidence of AMS (%), determined from both the ESQ and LLS, increased (P<0.05) from SL (0 +/- 0) to PreIAE (50 +/- 22) at 24 h of altitude exposure and decreased (P<0.05) from PreIAE to PostIAE (0 +/- 0). The severity of AMS (i.e. AMS cerebral symptom and LLS self-report scores) increased (P<0.05) from SL (0.02 +/- 0.02 and 0.17 +/- 0.17 respectively) to PreIAE (0.49 +/- 0.18 and 4.17 +/- 0.94 respectively) at 24 h of altitude exposure, and decreased (P<0.05) from PreIAE to PostIAE (0.03 +/- 0.02 and 0.83 +/- 0.31 respectively). Resting PETCO2 (mmHg) decreased (i.e. increase in ventilation; P<0.05) from SL (38 +/- 1) to PreIAE (32 +/- 1) at 24 h of altitude exposure and decreased further (P<0.05) from PreIAE to PostIAE (28 +/- 1). In addition, 24-h urine volumes were similar at SL, PreIAE and PostIAE. In conclusion, our findings suggest that 3 weeks of IAE provide an effective alternative to chronic altitude residence for increasing resting ventilation and reducing the incidence and severity of AMS.

After short-term exposure to high altitude (HA), men appear to be less sensitive to insulin than at sea level (SL). We hypothesized that the same would be true in women, that reduced insulin sensitivity would be directly related to the rise in plasma epinephrine concentrations at altitude, and that the addition of alpha-adrenergic blockade would potentiate the reduction. To test the hypotheses, 12 women consumed a high-carbohydrate meal at SL and after 16 h at simulated 4,300-m elevation (HA). Subjects were studied twice at each elevation: once with prazosin (Prz), an alpha(1)-adrenergic antagonist, and once with placebo (Pla). Mathematical models were used to assess insulin resistance based on fasting [homeostasis model assessment of insulin resistance (HOMA-IR)] and postprandial [composite model insulin sensitivity index (C-ISI)] glucose and insulin concentrations. Relative to SL-Pla (HOMA-IR: 1.86 +/- 0.35), insulin resistance was greater in HA-Pla (3.00 +/- 0.45; P < 0.05), SL-Prz (3.46 +/- 0.51; P < 0.01), and HA-Prz (2.82 +/- 0.43; P < 0.05). Insulin sensitivity was reduced in HA-Pla (C-ISI: 4.41 +/- 1.03; P < 0.01), SL-Prz (5.73 +/- 1.01; P < 0.05), and HA-Prz (4.18 +/- 0.99; P < 0.01) relative to SL-Pla (8.02 +/- 0.92). Plasma epinephrine was significantly elevated in HA-Pla (0.57 +/- 0.08 ng/ml; P < 0.01), SL-Prz (0.42 +/- 0.07; P < 0.05), and HA-Prz (0.82 +/- 0.07; P < 0.01) relative to SL-Pla (0.28 +/- 0.04), but correlations with HOMA-IR, HOMA-beta-cell function, and C-ISI were weak. In women, short-term exposure to simulated HA reduced insulin sensitivity compared with SL. The change does not appear to be directly mediated by a concurrent rise in plasma epinephrine concentrations.