Chronic mountain sickness, which affects permanent residents of high altitudes, is the outcome of a progressive loss of ventilatory rate which naturally occurs with age and resulting in excessive hypoxemia and polycythemia. A theoretical model predicts the progressive failure of homeostatic control of the hemoglobin concentration when the values increase above those found at sea level. This is confirmed by lack of feedback mechanism between high altitude erythrocytosis and serum erythropoietin. The results of epidemiological studies are in agreement with the physiological findings. In a male population living at 4,300 m, an increase with age of the prevalences of excessive erythrocytosis (Hb > 213 g/l), blood oxygen saturation < 83%, headaches and a high score of symptoms of chronic mountain sickness has been found. The studies suggest the possibility that in addition to an accentuated hypoxemia, the excessive erythrocytosis may also result from an overreaction of the bone marrow to a fixed level of hypoxemia in ageing individuals.

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.

Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO(2) (PET(CO(2)), Torr) and end-tidal O(2) (PET(O(2)), Torr), arterial oxygen saturation (Sa(O(2)), %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco (n = 33; 4,300 m) aged 26--62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower PET(O(2)) (48 +/- 4 vs. 53 +/- 2 Torr, P = 0.005) and Sa(O(2)) levels (82 +/- 12 vs. 88 +/- 12%, P < 0.005) and higher PET(CO(2)) (34 +/- 2 vs. 29 +/- 3 Torr, P = 0.005) and Hb concentration (19 +/- 1 vs. 14 +/- 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with PET(CO(2)) and positively correlated with PET(O(2)) and Sa(O(2)). No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle.

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High-altitude (HA) natives have blunted ventilatory sensitivities to hypoxia, and it is uncertain whether this blunting is reversible on migration to sea level (SL). To study this, the ventilatory sensitivities to hypoxia of HA natives residing near SL were compared with those of SL natives. Two studies were performed. In study A, 24 HA subjects who had lived above 3,000 m for an average of 14 yr and had been resident at SL for an average of 23 yr were compared with 23 SL controls. In study B, 25 HA subjects who had lived above 3,500 m for at least 20 yr and had been resident at SL for no more than 5 yr were compared with 25 SL controls. Hypoxic sensitivities were assessed by breathing seven progressively more hypoxic gas mixtures that contained progressively more CO2 in an attempt to maintain isocapnia throughout. The ventilatory sensitivities to hypoxia (l . min-1 . %-1 . m-2) did not differ significantly (by analysis of variance) between HA and SL natives in either study A (-0.51 +/- 0.25, mean +/- SD) or study B (-0.34 +/- 0. 15), but the ventilatory sensitivities did differ significantly between the two studies for reasons which are not entirely clear. We conclude that HA natives residing at SL, even if previously at HA for >20 yr, do not maintain the severely blunted hypoxic responses that have been reported in such individuals.