Heinrich Erica C, Orr Jeremy E, Gilbertson Dillon, Anza-Ramirez Cecilia, DeYoung Pamela N, Djokic Matea A, Corante Noemi, Vizcardo-Galindo Gustavo, Macarlupu Jose L, Gaio Eduardo, Powell Frank L, Malhotra Atul, Villafuerte Francisco C, Simonson Tatum S
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, United States.
Laboratorio de Fisiología Comparada/Fisiología del Transporte de Oxígen, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
Front Physiol. 2020 May 6;11:437. doi: 10.3389/fphys.2020.00437. eCollection 2020.
Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals ( = 63 men; = 46 women), and sleep measures in 45 of these participants ( = 22 men; = 23 women). In both men and women, high Hct was associated with low daytime SpO ( < 0.001 and < 0.002, respectively) and decreased sleep SpO (mean, nadir, and time <80%; all < 0.02). In men, high Hct was also associated with increased end-tidal P ( < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO in men ( < 0.01) and women ( < 0.009) and with lower nadir sleep SpO in women ( < 0.02). Decreased ventilatory responses to CO were associated with more time below 80% SpO during sleep in men ( < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct ( < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations.
安第斯高地居民面临慢性缺氧的挑战,与其他高海拔人群相比,许多人表现出红细胞压积(Hct)升高和通气减弱。虽然许多安第斯人会患上慢性高山病(CMS)和红细胞增多症,但安第斯男性和女性的Hct差异显著,这可能是由通气控制和/或睡眠事件中的个体差异导致的,这些差异会加重低氧血症。为了验证这一假设,我们量化了安第斯男性和女性静息通气与通气化学反射、睡眠去饱和、呼吸紊乱和Hct之间的关系。对109名个体(男性63名;女性46名)进行了通气测量,其中45名参与者(男性22名;女性23名)进行了睡眠测量。在男性和女性中,高Hct均与白天低SpO(分别为P<0.001和P<0.002)以及睡眠SpO降低(平均值、最低点和时间<80%;均为P<0.02)相关。在男性中,高Hct还与呼气末P增加相关(P<0.009)。虽然对低氧和高碳酸血症的通气反应不能预测Hct,但低氧通气反应降低与男性(P<0.01)和女性(P<0.009)白天较低的SpO以及女性睡眠SpO最低点较低(P<0.02)相关。对CO的通气反应降低与男性睡眠期间SpO低于80%的时间更长相关(P<0.05)。在考虑年龄、BMI和睡眠期间的SpO后,阻塞性呼吸暂停指数和呼吸暂停低通气指数也能预测男性的Hct和CMS评分。最后,Hct较高的男性对低氧的心率反应较低(P<0.0001)。这些数据支持以下观点:通气不足和对低氧的通气敏感性降低与白天和夜间SpO水平降低相关,这可能会加剧安第斯男性和女性红细胞生成的刺激。然而,需要进行干预性和纵向研究来确定这些关联之间的因果关系。