Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man.

By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude.     

Red cell function at extreme altitude on Mount Everest

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude.     

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.     

Changes in the blood flow of the primary carotid and its branches during modifications of the O2 and CO2 composition of alveolar gas]

We measured common carotid blood flow using a range gated Doppler velocimeter, and internal and external blood velocities using a continuous Doppler in 20 lowlanders at sea level, under normal barometric pressure, in 10 subjects in an altitude chamber under a barometric pressure of 462 Torr (61.6 KPa) and then in 5 of them over a 3-weeks period at 3850 m of elevation (475 Torr = 63.3 KPa). The same measurements were also performed in 20 permanent residents at 3850 m. Common carotid blood flow was 15% higher in all subjects exposed to high altitude, due to a lowering in downstream resistances since systemic blood pressure did not change at high altitude. The increase in common carotid blood flow was the result of an immediate increase in internal carotid blood velocities observed in the altitude chamber as well as after the arrival at high altitude, but a few days later those velocities in the internal carotid artery declined to values similar to those observed at sea level. In the same time velocities in external carotid artery rose at high altitude, remained steadily elevated and the result is a permanent increase in common carotid blood flow at altitude. In all subjects we performed the same measurements, during an acute inhalation of gas mixtures to try to quantify the mechanisms controlling the changes in common carotid blood flow while changing gas inhalation. In the limits of the variations in PO2 (60 to 400 Torr) and in PCO2 (30 to 50 Torr) the stimulation by CO2 is twice more efficient than the O2 stimulation on vasomotion.     

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.     

Cerebral interstitial fluid acid-base status follows arterial acid-base perturbations

Cerebral interstitial fluid (ISF) pH of ventral medulla or thalamus, cisternal cerebrospinal fluid (CSF) pH, and arterial blood pH, PCO2, and [HCO-3] were measured in chloralose-urethan-anesthetized, gallamine-paralyzed New Zealand White rabbits during 30-min episodes of either HCl or NaHCO3 intravenous infusions. ISF pH was measured continuously with glass microelectrodes (1- to 2-microns tip diameter). Cisternal CSF pH was measured continuously with an indwelling pH probe (1-mm tip diameter). Both ventral medullary and thalamic ISF [H+] changed significantly, whereas arterial PCO2 remained constant. CSF [H+] did not change. We conclude from these data that 1) changes in blood acid-base conditions are rapidly reflected in cerebral ISF and 2) transient differences in [H+] and [HCO-3] can exist between cerebral ISF and CSF.     

Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous opioids and ventilatory adaptation to prolonged hypoxia in goats

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.     

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.     

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 +/- 0.20 l/min at sea level to 1.17 +/- 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 +/- 1 Torr and PCO2 = 11 +/- 1 Torr, with a marked reduction in mixed venous PO2 [14.8 +/- 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.     

Ventilation in newborn rats after gestation at simulated high altitude

Pregnant rats were kept at a simulated altitude of 4,500 m (PO2 91 Torr) for the whole of gestation and returned to sea level 1 day after giving birth. During pregnancy, body weight gain and food intake were approximately 30% less than in controls at sea level. Measurements were made on the 1-day-old (HYPO) pups after a few hours at sea level. In normoxia, ventilation (VE) measured by flow plethysmography was more (+17%) and O2 consumption (VO2) measured by a manometric method was less (-19%) than in control (CONT) pups; in HYPO pups VE/VO2 was 44% greater than in CONT pups. In acute hyperoxia, VE/VO2 of HYPO and CONT pups decreased by a similar amount (15-20%), indicating some limitation in O2 availability for both groups of pups in normoxia. However, VE/VO2 of HYPO pups, even in hyperoxia, remained above (+34%) that of CONT pups. HYPO pups weighed slightly less than CONT pups, their lungs were hypoplastic, and their hearts were a larger fraction of body weight. An additional group of female rats was acclimatized (8 days) to high altitude before insemination. During pregnancy, body weight gain and food intake of these females were similar to those of pregnant rats at sea level. Measurements on the 1-day-old pups of this group were similar to those of HYPO pups. We conclude that newborn rats born after hypoxic gestation present metabolic adaptation (low VO2) and acclimatization (high VE/VO2), possibly because of hypoxemia. Maternal acclimatization before insemination substantially alters maternal growth in hypoxia but does not affect neonatal outcome.     

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia.

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O2 fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2 fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA ( approximately 5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 +/- 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 +/- 3 vs. -5 +/- 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by approximately 50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.     

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.     

Effects of acetazolamide on cerebral acid-base balance

Acetazolamide (AZ) inhibition of brain and blood carbonic anhydrase increases cerebral blood flow by acidifying cerebral extracellular fluid (ECF). This ECF acidosis was studied to determine whether it results from high PCO2, carbonic acidosis (accumulation of H2CO3), or lactic acidosis. Twenty rabbits were anesthetized with pentobarbital sodium, paralyzed, and mechanically ventilated with 100% O2. The cerebral cortex was exposed and fitted with thermostatted flat-surfaced pH and PCO2 electrodes. Control values (n = 14) for cortex ECF were pH 7.10 +/- 0.11 (SD), PCO2 42.2 +/- 4.1 Torr, PO2 107 +/- 17 Torr, HCO3- 13.8 +/- 3.0 mM. Control values (n = 14) for arterial blood were arterial pH (pHa) 7.46 +/- 0.03 (SD), arterial PCO2 (PaCO2) 32.0 +/- 4.1 Torr, arterial PO2 (PaO2) 425 +/- 6 Torr, HCO3- 21.0 +/- 2.0 mM. After intravenous infusion of AZ (25 mg/kg), end-tidal PCO2 and brain ECF pH immediately fell and cortex PCO2 rose. Ventilation was increased in nine rabbits to bring ECF PCO2 back to control. The changes in ECF PCO2 then were as follows: pHa + 0.04 +/- 0.09, PaCO2 -8.0 +/- 5.9 Torr, HCO3(-)-2.7 +/- 2.3 mM, PaO2 +49 +/- 62 Torr, and changes in cortex ECF were as follows: pH -0.08 +/- 0.04, PCO2 -0.2 +/- 1.6 Torr, HCO3(-)-1.7 +/- 1.3 mM, PO2 +9 +/- 4 Torr. Thus excess acidity remained in ECF after ECF PCO2 was returned to control values. The response of intracellular pH, high-energy phosphate compounds, and lactic acid to AZ administration was followed in vivo in five other rabbits with 31P and 1H nuclear magnetic resonance spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.).

Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field.     

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.     

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.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Incomplete compensation of CSF [H+] in man during acclimatization to high altitude (48300 M).

This study has assessed the regulation of arterial blood and cerebrospinal fluid acid-base status in seven healthy men, at 250 m altitude and after 5 and 10-11 days sojourn at 4,300 m altitude (PaO2 = 39 mmHg day 1 to 48 mmHg day 11). We assumed that observed changes in lumbar spinal fluid acid-base status paralleled those in cisternal CSF, under these relatively steady-state conditions. Ventilatory acclimatization during the sojourn (-14 mmHg PaCO2 at day 11) was accompanied by: 1) reductions in [HCO3-] (-5 to -7 meq/1) which were similar in arterial blood and CSF; 2) substantial, yet incomplete, compensation (70-75%) of both CSF and blood pH; and 3) a level of CSF pH which was maintained significantly alkaline (+0.05 +/- 0.01) to normoxic control values. These data at 4,300 m confirmed and extended our previous findings for more moderate conditions of chronic hypoxia. It was postulated that the magnitude and time course of pH compensation in the CSF during chronic hypoxia and/or hypocapnia are determined by corresponding changes in plasma [HCO2-].