Bernardi Luciano, Roach Robert C, Keyl Cornelius, Spicuzza Lucia, Passino Claudio, Bonfichi Maurizio, Gamboa Alfredo, Gamboa Jorge, Malcovati Luca, Schneider Annette, Casiraghi Nadia, Mori Antonio, Leon-Velarde Fabiola
Clinica Medica 2, IRCCS S. Matteo, University of Pavia, Italy.
Adv Exp Med Biol. 2003;543:161-75.
Polycythemia is one of the key factors involved in the chronic mountain sickness syndrome, a condition frequent in Andean natives but whose causes still remain unclear. In theory, polycythemia may be secondary to abnormalities in ventilation, occurring during day or night (e.g. due to sleep abnormalities) stimulating excessive erythropoietin (Epo) production, or else it may result from either autogenous production, or from co-factors like cobalt. To assess the importance of these points, we studied subjects with or without polycythemia, born and living in Cerro de Pasco (Peru, 4330m asl, CP) and evaluated the relationship between Epo and respiratory variables both in CP and sea level. We also assessed the relationship between sleep abnormalities and the circadian rhythm of Epo. Polycythemic subjects showed higher Epo in all conditions, lower SaO2 and hypoxic ventilatory response, higher physiological dead space and higher CO2, suggesting ventilatory inefficiency. Epo levels could be highly modified by the level of oxygenation, and were related to similar directional changes in SaO2. Cobalt levels were normal in all subjects and correlated poorly with hematologic variables. The diurnal variations in Epo were grossly abnormal in polycythemic subjects, with complete loss of the circadian rhythm. These abnormalities correlated with the levels of hypoxemia during the night, but not with sleep abnormalities, which were only minor even in polycythemic subjects. The increased Epo production is mainly related to a greater ventilatory inefficiency, and not to altered sensitivity to hypoxia, cobalt or sleep abnormalities. Improving oxygenation can represent a possible therapeutic option for this syndrome.
红细胞增多症是慢性高原病综合征的关键因素之一，这种病症在安第斯原住民中很常见，但其病因仍不清楚。理论上，红细胞增多症可能继发于通气异常，这种异常在白天或夜间发生（例如由于睡眠异常），刺激促红细胞生成素（Epo）过度产生，或者它可能源于自身产生，或者源于钴等辅助因素。为了评估这些因素的重要性，我们研究了出生并生活在塞罗德帕斯科（秘鲁，海拔4330米，CP）的有或没有红细胞增多症的受试者，并评估了CP和海平面时Epo与呼吸变量之间的关系。我们还评估了睡眠异常与Epo昼夜节律之间的关系。红细胞增多症患者在所有情况下Epo水平都较高，SaO2和低氧通气反应较低，生理死腔和CO2较高，提示通气效率低下。Epo水平可因氧合水平而发生高度改变，并与SaO2的类似方向变化相关。所有受试者的钴水平均正常，且与血液学变量相关性较差。红细胞增多症患者Epo的昼夜变化明显异常，昼夜节律完全丧失。这些异常与夜间低氧血症水平相关，但与睡眠异常无关，即使在红细胞增多症患者中睡眠异常也很轻微。Epo产生增加主要与通气效率降低有关，而不是与对缺氧、钴或睡眠异常的敏感性改变有关。改善氧合可能是该综合征的一种可能治疗选择。
