Headache at high altitude is not related to internal carotid arterial blood velocity

The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role.     

Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude

To investigate the effects of both exercise and acute exposure to high altitude on ventilation-perfusion (VA/Q) relationships in the lungs, nine young men were studied at rest and at up to three different levels of exercise on a bicycle ergometer. Altitude was simulated in a hypobaric chamber with measurements made at sea level (mean barometric pressure = 755 Torr) and at simulated altitudes of 5,000 (632 Torr), 10,000 (523 Torr), and 15,000 ft (429 Torr). VA/Q distributions were estimated using the multiple inert gas elimination technique. Dispersion of the distributions of blood flow and ventilation were evaluated by both loge standard deviations (derived from the VA/Q 50-compartment lung model) and three new indices of dispersion that are derived directly from inert gas data. Both methods indicated a broadening of the distributions of blood flow and ventilation with increasing exercise at sea level, but the trend was of borderline statistical significance. There was no change in the resting distributions with altitude. However, with exercise at high altitude (10,000 and 15,000 ft) there was a significant increase in dispersion of blood flow (P less than 0.05) which implies an increase in intraregional inhomogeneity that more than counteracts the more uniform topographical distribution that occurs. Since breathing 100% O2 at 15,000 ft abolished the increased dispersion, the greater VA/Q mismatching seen during exercise at altitude may be related to pulmonary hypertension.     

Internal carotid and vertebral arterial flow velocity in men at high altitude

Cerebral blood flow increases at high altitude, but the mechanism of the increase and its role in adaptation to high altitude are unclear. We hypothesized that the hypoxemia at high altitude would increase cerebral blood flow, which would in turn defend O2 delivery to the brain. Noninvasive Doppler ultrasound was used to measure the flow velocities in the internal carotid and the vertebral arteries in six healthy male subjects. Within 2-4 h of arrival on Pikes Peak (4,300 m), velocities in both arteries were slightly and not significantly increased above sea-level values. By 18-44 h a peak increase of 20% was observed (combined P less than 0.025). Subsequently (days 4-12) velocities declined to values similar to those at sea level. At altitude the lowest arterial O2 saturation (SaO2) and the highest end-tidal PCO2 was observed on arrival. By day 4 and thereafter, when the flow velocities had returned toward sea-level values, hemoglobin concentration and SaO2 were increased over initial high-altitude values such that calculated O2 transport values were even higher than those at sea level. Although the cause of the failure for cerebral flow velocity to increase on arrival is not understood, the subsequent increase may act to defend brain O2 transport. With further increase in hemoglobin and SaO2 over time at high altitude, flow velocity returned to sea-level values.     

Operation Everest II: preservation of cardiac function at extreme altitude

Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.     

Effects of hypobaria on lung fluid balance in awake sheep

Effects of hypobaria on lung fluid balance were studied in five awake sheep with chronic lung lymph fistulas using a decompression chamber. Each sheep was exposed to three conditions of 6,600-m-simulated high altitude in random order as follows: 1) 6,600-m-simulated hypoxic hypobaria (barometric pressure 326 Torr, 21% inspired O2 fraction), 2) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction), and 3) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction) after pretreatment with a 2-h pure O2 inhalation (i.e., denitrogenation) to allow elimination of dissolved gases, especially N2, from the blood and tissues. We observed that under both hypoxic hypobaria and normoxic hypobaria, lung lymph flow (Qlym) significantly increased from the base-line values of 6.4 +/- 0.3 to 13.0 +/- 1.0 ml/h and 6.0 +/- 0.2 to 9.4 +/- 0.3 ml/h, respectively (P less than 0.05) and that the lymph-to-plasma protein concentration ratio remained unchanged. Moreover, pretreatment with a 2-h denitrogenation inhibited the increase in Qlym. These results suggest that rapid exposure to hypobaria causes an increase in pulmonary vascular permeability and that intravascular air bubble formation may account for this permeability change.     

Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m).

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han ("Chinese") 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.     

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.

In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.     

Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen

High altitude increases pulmonary arterial pressure (PAP), but no measurements have been made in humans above 4,500 m. Eight male athletic volunteers were decompressed in a hypobaric chamber for 40 days to a barometric pressure (PB) of 240 Torr, equivalent to the summit of Mt. Everest. Serial hemodynamic measurements were made at PB 760 (sea level), 347 (6,100 m), and 282/240 Torr (7,620/8,840 m). Resting PAP and pulmonary vascular resistance (PVR) increased from sea level to maximal values at PB 282 Torr from 15 +/- 0.9 to 34 +/- 3.0 mmHg and from 1.2 +/- 0.1 to 4.3 +/- 0.3 mmHg.l-1 X min, respectively. During near maximal exercise PAP increased from 33 +/- 1 mmHg at sea level to 54 +/- 2 mmHg at PB 282 Torr. Right atrial and wedge pressures were not increased with altitude. Acute 100% O2 breathing lowered cardiac output and PAP but not PVR. Systemic arterial pressure and resistance did not rise with altitude but did increase with O2 breathing, indicating systemic control differed from the lung circulation. We concluded that severe chronic hypoxia caused elevated pulmonary resistance not accompanied by right heart failure nor immediately reversed by O2 breathing.     

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary gas exchange in humans exercising at sea level and simulated altitude

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.     

Local sweating and cutaneous blood flow during exercise in hypobaric environments

The effect of acute hypobaric hypoxia on local sweating and cutaneous blood flow was studied in four men and four women (follicular phase of menstrual cycle), who exercised at 60% of their altitude-specific peak aerobic power for 35 min at barometric pressures (PB) of 770 Torr (sea level), 552 Torr (2,596 m), and 428 Torr (4,575 m) at an ambient temperature of 30 degrees C. We measured esophageal temperature (Tes), mean skin temperature (Tsk, 8 sites), and local sweating (ms) from dew-point sensors attached to the skin at the chest, arm, and thigh. Skin blood flow (SkBF) of the forearm was measured once each minute by venous occlusion plethysmography. There were no gender differences in the sensitivity (slope) or the threshold of either ms/Tes or SkBF/Tes at any altitude. No change in the Tes for sweating onset occurred with altitude. The mean slopes of the ms/Tes relationships for the three regional sites decreased with increasing altitude, although these differences were not significant between the two lower PBS. The slope of SkBF/Tes was reduced in five of the eight subjects at 428 Torr. Enhanced body cooling as a response to the higher evaporative capacity of the environment is suggested as a component of these peripheral changes occurring in hypobaric hypoxia.     

Oxygen transport to exercising leg in chronic hypoxia

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.     

The 1988 Stevenson Memorial lecture. Physiological responses to severe hypoxia in man

Recent measurements at extreme altitude and in low pressure chamber simulations have clarified the human responses to extreme hypoxia. Man can only tolerate the severe oxygen deprivation of great altitudes by an enormous increase in ventilation which has the advantage of defending the alveolar PO2 against the reduced inspired PO2. Nevertheless the arterial PO2 on the Everest summit is less than 30 Torr (1 Torr = 133.3 Pa). An interesting consequence of the hyperventilation is that the respiratory alkalosis greatly increases the oxygen affinity of the hemoglobin and assists in oxygen loading by the pulmonary capillary. The severe hypoxemia impairs the function of many organ systems including the central nervous system, and there is evidence of residual impairment of memory and manipulative skill in climbers returning from great altitudes. At the altitude of Mt. Everest, maximal oxygen uptake is reduced to 20-25% of its sea level value, and it is exquisitely sensitive to barometric pressure. It is likely that the seasonal variation of barometric pressure affects the ability of man to reach the summit without supplementary oxygen.     

Operation Everest II: pulmonary gas exchange during a simulated ascent of Mt. Everest

Eight normal subjects were decompressed to barometric pressure (PB) = 240 Torr over 40 days. The ventilation-perfusion (VA/Q) distribution was estimated at rest and during exercise [up to 80-90% maximal O2 uptake (VO2 max)] by the multiple inert gas elimination technique at sea level and PB = 428, 347, 282, and 240 Torr. The dispersion of the blood flow distribution increased by 64% from rest to 281 W, at both sea level and at PB = 428 Torr (heaviest exercise 215 W). At PB = 347 Torr, the increase was 79% (rest to 159 W); at PB = 282 Torr, the increase was 112% (108 W); and at PB = 240 Torr, the increase was 9% (60 W). There was no significant correlation between the dispersion and cardiac output, ventilation, or pulmonary arterial wedge pressure, but there was a correlation between the dispersion and mean pulmonary arterial pressure (r = 0.49, P = 0.02). When abnormal, the VA/Q pattern generally had perfusion in lung units of zero or near zero VA/Q combined with units of normal VA/Q. Alveolar-end-capillary diffusion limitation of O2 uptake (VO2) was observed at VO2 greater than 3 l/min at sea level, greater than 1-2 l/min VO2 at PB = 428 and 347 Torr, and at higher altitudes, at VO2 less than or equal to 1 l/min. These results show variable but increasing VA/Q mismatch with long-term exposure to both altitude and exercise. The VA/Q pattern and relationship to pulmonary arterial pressure are both compatible with alveolar interstitial edema as the primary cause of inequality.     

Oxygen transport during steady-state submaximal exercise in chronic hypoxia

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic Postconditioning Fails to Protect against Neonatal Cerebral Stroke

The lack of efficient neuroprotective strategies for neonatal stroke could be ascribed to pathogenic ischemic processes differentiating adults and neonates. We explored this hypothesis using a rat model of neonatal ischemia induced by permanent occlusion of the left distal middle cerebral artery combined with 50 min of occlusion of both common carotid arteries (CCA). Postconditioning was performed by repetitive brief release and occlusion (30 s, 1 and/or 5 min) of CCA after 50 min of CCA occlusion. Alternative reperfusion was generated by controlled release of the bilateral CCA occlusion. Blood-flow velocities in the left internal carotid artery were measured using color-coded pulsed Doppler ultrasound imaging. Cortical perfusion was measured using laser Doppler. Cerebrovascular vasoreactivity was evaluated after inhalation with the hypercapnic gas or inhaled nitric oxide (NO). Whatever the type of serial mechanical interruptions of blood flow at reperfusion, postconditioning did not reduce infarct volume after 72 hours. A gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. The absence of acute hyperemia during early CCA re-flow, and the lack of NO-dependent vasoreactivity in P7 rat brain could in part explain the inefficiency of ischemic postconditioning after ischemia-reperfusion.     

Nocturnal periodic breathing at altitudes of 6,300 and 8,050 m

Nocturnal periodic breathing was studied in eight well-acclimatized subjects living at an altitude of 6,300 m [barometric pressure (PB) 350-352 Torr] for 3-5 wk and in four subjects during one night at 8,050 m altitude (PB 281-285 Torr). The measurements at 6,300 m included tidal volume by inductance plethysmography, arterial O2 saturation by ear oximetry (calibrated by arterial blood samples), electrocardiogram (ECG), and electrooculogram. At 8,050 m, periodic breathing was inferred from the cyclical variation in heart rate obtained from a night-long ECG record. All subjects at 6,300 m altitude showed well-marked periodic breathing with apneic periods. Cycle length averaged 20.5 s with 7.9 s apnea. Minimal arterial O2 saturation averaged 63.4% corresponding to a PO2 of approximately 33 Torr, i.e., approximately 6 Torr lower than the normal value at rest during daytime. This was probably the most severe hypoxemia of the 24-h period. At 8,050 m altitude, the cycle length averaged 15.4 s, much longer than predicted by a theoretical model. Cyclical variations in heart rate caused by periodic breathing occurred in all subjects, but abnormal cardiac rhythms such as ventricular premature contractions were uncommon. The severe arterial hypoxemia caused by periodic breathing may be an important determinant of tolerance to these great altitudes.     

Body structure and respiratory efficiency among high altitude Himalayan populations

To understand the morphological and physiological variations among the temporary and permanent residents of high altitude, this study was undertaken at Leh, Ladakh. It is situated at 3500 m (11500 feet) above sea level, the mean barometric pressure was 500 tors and air temperature varied from 2 degrees C to 20 degrees C. The highland Tibetans showed broadest chest and most developed musculature closely followed by Ladakhi Bods. These high altude natives also displayed significantly higher value of vital capacity, forced vital capacity, and inspiratory capacity. The better respiratory efficiency observed among high altitude residents indicates higher degree of adaptation to high altitude hypoxia. Temporary residents were observed to be tallest and fattest with lower trunk fat predominance of all the four groups and showed narrowest chest and lower respiratory efficiency as compared to high altitude natives. The duration of stay at high altitude has clearly brought about a perceptible difference in body dimensions and respiratory functions of various groups of adult males studied at same altitude.     

Does cerebral oxygen delivery limit incremental exercise performance?

Previous studies have suggested that a reduction in cerebral oxygen delivery may limit motor drive, particularly in hypoxic conditions, where oxygen transport is impaired. We hypothesized that raising end-tidal Pco(2) (Pet(CO(2))) during incremental exercise would increase cerebral blood flow (CBF) and oxygen delivery, thereby improving peak power output (W(peak)). Amateur cyclists performed two ramped exercise tests (25 W/min) in a counterbalanced order to compare the normal, poikilocapnic response against a clamped condition, in which Pet(CO(2)) was held at 50 Torr throughout exercise. Tests were performed in normoxia (barometric pressure = 630 mmHg, 1,650 m) and hypoxia (barometric pressure = 425 mmHg, 4,875 m) in a hypobaric chamber. An additional trial in hypoxia investigated effects of clamping at a lower Pet(CO(2)) (40 Torr) from ～75 to 100% W(peak) to reduce potential influences of respiratory acidosis and muscle fatigue imposed by clamping Pet(CO(2)) at 50 Torr. Metabolic gases, ventilation, middle cerebral artery CBF velocity (transcranial Doppler), forehead pulse oximetry, and cerebral (prefrontal) and muscle (vastus lateralis) hemoglobin oxygenation (near infrared spectroscopy) were monitored across trials. Clamping Pet(CO(2)) at 50 Torr in both normoxia (n = 9) and hypoxia (n = 11) elevated CBF velocity (～40%) and improved cerebral hemoglobin oxygenation (～15%), but decreased W(peak) (6%) and peak oxygen consumption (11%). Clamping at 40 Torr near maximal effort in hypoxia (n = 6) also improved cerebral oxygenation (～15%), but again limited W(peak) (5%). These findings demonstrate that increasing mass cerebral oxygen delivery via CO(2)-mediated vasodilation does not improve incremental exercise performance, at least when accompanied by respiratory acidosis.