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.     

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.     

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)     

Propranolol does not impair exercise oxygen uptake in normal men at high altitude

Decreased maximal O2 uptake (VO2max) and stimulation of the sympathetic nervous system have been previously shown to occur at high altitude. We hypothesized that tachycardia mediated by beta-adrenergic stimulation acted to defend VO2max at high altitude. Propranolol treatment beginning before high-altitude (4,300 m) ascent reduced heart rate during maximal and submaximal exercise in six healthy men treated with propranolol (80 mg three times daily) compared with five healthy subjects receiving placebo (lactose). Compared with sea-level values, the VO2max fell on day 2 at high altitude, but the magnitude of fall was similar in the placebo and propranolol treatment groups (26 +/- 6 vs. 32 +/- 5%, P = NS) and VO2max remained similar at high altitude in both groups once treatment was discontinued. During 30 min of submaximal (80% of VO2max) exercise, propranolol-treated subjects maintained O2 uptake levels that were as large as those in placebo subjects. The maintenance of maximal or submaximal levels of O2 uptake in propranolol-treated subjects at 4,300 m could not be attributed to increased minute ventilation, arterial O2 saturation, or hemoglobin concentration. Rather, it appeared that propranolol-treated subjects maintained O2 uptake by transporting a greater proportion of the O2 uptake with each heartbeat. Thus, contrary to our hypothesis, beta-adrenergic blockade did not impair maximal or submaximal O2 uptake at high altitude due perhaps to compensatory mechanisms acting to maintain stroke volume and cardiac output.     

Alterations in the coronary circulation of man following ascent to 3,100 m altitude.

Alterations in coronary blood flow associated with adaptation to high altitude were examined. Three normal men native to low altitude were studied, first at sea level, and again after 10 days' sojourn at 3,100 m altitude. During rest at high altitude, a 32% decrease in coronary blood flow was largely offset by a 28% increase in coronary arterial O2 extraction to maintain myocardial O2 delivery. The increase in O2 extraction resulted mainly from a decrease in coronary sinus blood O2 content and saturation. However, coronary sinus O2 tension remained constant, implying a decrease in the affinity of hemoglobin for O2. These observations are consistent with the hypothesis that coronary blood flow is regulated to maintain constant myocardial tissue O2 tension (as reflected here by coronary sinus blood O2 tension). The absence of a decrease in coronary sinus O2 tension or a decrease in myocardial lactate extraction imply that myocardial hypoxia did not develop. Therefore, myocardial hypoxia is not the basis for the decrease in cardiac stroke volume at high altitude reported previously and also observed in the present study.     

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders.

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.     

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.     

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.     

Glucoregulatory hormones in man at high altitude

Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.     

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)     

Serum erythropoietin in humans at high altitude and its relation to plasma renin

Serum immunoreactive erythropoietin (siEp) was estimated in samples collected from members of two scientific and mountaineering expeditions, to Mount Kongur in Western China and to Mount Everest in Nepal. SiEp was increased above sea-level control values 1 and 2 days after arrival at 3,500 m and remained high on ascent to 4,500 m. Thereafter, while subjects remained at or above 4,500 m, siEp declined, and by 22 days after the ascent to 4,500 m was at control values but increased on ascent to higher altitude. Thus siEp was at a normal level during the maintenance of secondary polycythemia from high-altitude exposure. On descent, with removal of altitude hypoxia, siEp decreased, but despite secondary polycythemia levels remained measurable and in the range found in subjects normally resident at sea level. On Mount Everest, siEp was significantly (P less than 0.01) elevated above preexpedition sea-level controls after 2-4 wk at or above 6,300 m. There was no correlation between estimates of siEp and plasma renin activity in samples collected before and during both expeditions.     

Cerebral blood flow velocity responses to hypoxia in subjects who are susceptible to high-altitude pulmonary oedema

Cerebral blood flow increases on exposure to high altitude, and perhaps more so in subjects who develop acute mountain sickness. We determined cerebral blood flow by transcranial Doppler ultrasound of the middle cerebral artery at sea level, in normoxia (fraction of inspired O2, F(I)O2 0.21), and during 15-min periods of either hypoxic (F(I)O2 0.125) or hyperoxic (F(I)O2 1.0) breathing, in 7 subjects with previous high-altitude pulmonary oedema, 6 climbers who had previously tolerated altitudes between 6000 m and 8150 m, and in 20 unselected controls. Hypoxia increased mean middle cerebral artery flow velocity from 69 (3) to 83 (4) cm x s(-1) (P<0.001) in the controls, from 63 (3) to 75 (3) cm x s(-1) (P<0.001) in the high-altitude pulmonary-oedema-susceptible subjects, and from 58 (4) to 70 (4) cm x s(-1) (P<0.001) in the successful high-altitude climbers. Hyperoxia decreased mean middle cerebral flow velocity to 60 (3) cm x s(-1) (P<0.001), 53 (3) cm x s(-1) (P<0.01), and 49 (3) cm x s(-1) (P<0.01) in the controls, high-altitude pulmonary-oedema-susceptible, and high-altitude climbers, respectively. We conclude that a transcranial Doppler-based estimate of cerebral blood flow is affected by hypoxic and hyperoxic breathing, and that it is not predictive of tolerance to high altitude.     

Exercise VE and physical performance at altitude are not affected by menstrual cycle phase.

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.     

Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep

Although the influence of altitude acclimatization on respiration has been carefully studied, the associated changes in hypoxic and hypercapnic ventilatory responses are the subject of controversy with neither response being previously evaluated during sleep at altitude. Therefore, six healthy males were studied at sea level and on nights 1, 4, and 7 after arrival at altitude (14,110 ft). During wakefulness, ventilation and the ventilatory responses to hypoxia and hypercapnia were determined on each occasion. During both non-rapid-eye-movement and rapid-eye-movement sleep, ventilation, ventilatory pattern, and the hypercapnic ventilatory response (measured at ambient arterial O2 saturation) were determined. There were four primary observations from this study: 1) the hypoxic ventilatory response, although similar to sea level values on arrival at altitude, increased steadily with acclimatization up to 7 days; 2) the slope of the hypercapnic ventilatory response increased on initial exposure to a hypoxic environment (altitude) but did not increase further with acclimatization, although the position of this response shifted steadily to the left (lower PCO2 values); 3) the sleep-induced decrements in both ventilation and hypercapnic responsiveness at altitude were equivalent to those observed at sea level with similar acclimatization occurring during wakefulness and sleep; and 4) the quantity of periodic breathing during sleep at altitude was highly variable and tended to occur more frequently in individuals with higher ventilatory responses to both hypoxia and hypercapnia.     

Effect of altitude exposure on thermoregulatory response of man to cold.

The thermoregulatory responses to 10 degrees C (for 3 h) were investigated in 1) 12 natives from sea level (lowlanders) at 150 m, and on arrival at 3,350 and 4,340 m; 2) 6 of these during a 6-wk sojourn at 4,360 m, and on return to sea level; and 3) 5 natives from each of the two altitudes (highlanders) in their respective habitat, and after descent to 150 m. The cold-induced increase in the rate of O2 consumption (Vo2) of the lowlanders was significantly smaller at both altitudes than at sea level. It did not recover substantially during the 6 wk at altitude, but was restored to its initial rate on return to sea level. By contrast, visible shivering activity was augmented on arrival at altitude. It persisted throughout the 6 wk there, but was greatly depressed on return to sea level, despite the increased Vo2. Mean skin temperatures (Tsk) stabilized in the cold at significantly higher values at altitude. Rectal temperature (Tre) decreased similarly at all altitudes. Vo2 of the highlanders in the cold was significantly greater at sea level than at their resident altitudes, although shivering activity was less intense; Tsk stabilized at significantly lower levels at 150 m than at either altitude. These results indicate that altitude exposure reduces the calorigenic response of man to cold, and that this effect is not moderated by acclimatization to altitude, yet is reversible immediately on descent to sea level. The component of cold thermogenesis which appeared to be reduced by altitude exposure was nonshivering thermogenesis rather than visible shivering.     

Optimal hemoglobin concentration and high altitude: a theoretical approach for Andean men at rest.

The beneficial role of erythrocytosis for O2 transport has been questioned by evidence from bloodletting and hemodilution research as well as by studies suggesting the existence of an "optimal" hematocrit (Hct) or hemoglobin concentration ([Hb]) value. To assess to what extent erythrocytosis is beneficial in Andean men at high altitude, we examined and discussed optimal [Hb] using a mathematical approach by modeling the mixed (mean) venous Po2 (Pv(O2)) and arterial O2 content, considering for both the relation between [Hb] and arterial Po2. Relations of [Hb] to other physiological variables such as cardiac output and convective arterial O2 transport were also discussed, revealing the importance of Pv(O2) in this model. Our theoretical analysis suggests that increasing [Hb] allows increase and maintenance of Pv(O2) with only moderate declines in arterial Po2 as a consequence of moderate increases in altitude, reaching its maximum at the optimal [Hb] of 14.7 g/dl. Our analysis also shows that [Hb] corresponding to high arterial O2 content and O2 transport values is apparently not quite advantageous for improvement of oxygenation. Furthermore, chronic mountain sickness is discussed as an insightful example of the effects of excessive erythrocytosis at high altitude.     

Effects of a 1-yr stay at altitude on ventilation, metabolism, and work capacity.

The hypoxic and hypercapnic ventilatory drive, gas exchange, blood lactate and pyruvate concentrations, acid-base balance, and physical working capacity were determined in three groups of healthy males: 17 residents examined at sea level (group I), 24 sea-level natives residing at 1,680-m altitude for 1 yr and examined there (group II), and 17 sea-level natives residing at 3,650-m altitude for 1 yr and examined there (group III). The piecewise linear approximation technique was used to study the ventilatory response curves, which allowed a separate analysis of slopes during the first phase of slow increase in ventilation and the second phase of sharp increase. The hypoxic ventilatory response for both isocapnic and poikilocapnic conditions was greater in group II and even greater in group III. The first signs of consciousness distortion in sea-level residents appeared at an end-tidal O2 pressure level (4.09 +/- 0.56 kPa) higher than that of temporary residents of middle (3.05 +/- 0.12) and high altitude (2.90 +/- 0.07). The hypercapnic response was also increased, although to a lesser degree. Subjects with the highest hypoxic respiratory sensitivity at high altitude demonstrated greater O2 consumption at rest, greater ventilatory response to exercise, higher physical capacity, and a less pronounced anaerobic glycolytic flux but a lower tolerance to extreme hypoxia. That is, end-tidal O2 pressure that caused a distortion of the consciousness was higher in these subjects than in those with lower hypoxic sensitivity. Two extreme types of adaptation strategy can be distinguished: active, with marked reactions of "struggle for oxygen," and passive, with reduced O2 metabolism, as well as several intermediate types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altitude-induced erythrocytic 2,3-DPG and hemoglobin changes in rats of various ages.

Rats of various ages (2, 12, 24, and 40 mo of age) were exposed for 4 wk to either a simulated high altitude of 23,000 ft or to a Peoria, Ill., altitude of 650 ft above sea level. Hematocrit ratios, hemoglobin, and erythrocytic 2,3-diphospho-glycerate (2,3-DPG) concentrations were measured. Hematocrit and hemoglobin determinations revealed a decrease in erythrocytic content with increasing age, and the augmented erythropoietic response was seen in all age groups of animals as a result of altitude exposure. The maximal erythrocytic content of hemoglobin in the 40-mo-old animals was significantly lower than that of all other age groups. Erythrocytic 2,3-DPG levels were significantly changed by aging alone. In the 40-mo-old group there was a 35% increase over the next highest sea-level value. However, while erythrocytic 2,3-DPG content increased significantly in all other age groups following altitude exposure, it decreased 46% in the 40-mo-old group.     

Effect of simulated altitude erythrocythemia in women on hemoglobin flow rate during exercise

The effect of simulated altitude erythrocythemia on hemoglobin flow rate and maximal O2 uptake (VO2max) was determined for nine women sea-level residents. Test conditions included normoxia and normobaric hypoxia (16% O2-84% N2). Cycle tests were performed under normoxia (T1-N) and hypoxia (T1-H) at prereinfusion control and under hypoxia 48 h after a placebo infusion (T2-H) and 48 h after autologous infusion of 334 ml of erythrocytes (T3-H). Hematocrit (38.1-44.9%) and hemoglobin concentration (12.7-14.7 g.dl-1) increased from control to postreinfusion. At peak exercise, VO2max decreased from T1-N (2.40 l.min-1) to T1-H (2.15 l.min-1) then increased at T3-H (2.37 l.min-1). Maximal arterial-mixed venous O2 difference decreased from T1-N to T1-H and increased at T3-H. Cardiac output (Q), stroke volume, heart rate, and total peripheral resistance during maximal exercise were unchanged from T1-N through T3-H. Hemoglobin flow rate (Hb flow) at maximum did not change from T1-N to T1-H but increased at T3-H. When compared with submaximal values for T1-N, VO2 was unchanged at T1-H and T3-H; Q increased at T1-H and decreased at T3-H; arterial-mixed venous O2 difference decreased at T1-H and increased at T3-H; Hb flow did not change at T1-N but increased at T3-H. For young women, simulated altitude erythrocythemia increased peak Hb flow and decreased physiological altitude (227.8 m) but did not affect maximum cardiac output (Qmax).     

Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion

A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2-3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957-1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6-11 h (condition RN) and 4-5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors.