Barclay Holly, Mukerji Saptarshi, Kayser Bengt, O'Donnell Terrence, Tzeng Yu-Chieh, Hill Stephen, Knapp Katie, Legg Stephen, Frei Dan, Fan Jui-Lin
Wellington Medical Technology Group, Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand.
Centre for Translational Physiology, University of Otago, Wellington, New Zealand.
Exp Physiol. 2021 Jan;106(1):175-190. doi: 10.1113/EP088938.
What is the central question of this study? The pathophysiology of acute mountain sickness (AMS), involving the respiratory, renal and cerebrovascular systems, remains poorly understood. How do the early adaptations in these systems during a simulated altitude of 5000 m relate to AMS risk? What is the main finding and its importance? The rate of blood alkalosis and cerebral artery dilatation predict AMS severity during the first 10 h of exposure to a simulated altitude of 5000 m. Slow metabolic compensation by the kidneys of respiratory alkalosis attributable to a brisk breathing response together with excessive brain blood vessel dilatation might be involved in early development of AMS.
The complex pathophysiology of acute mountain sickness (AMS) remains poorly understood and is likely to involve maladaptive responses of the respiratory, renal and cerebrovascular systems to hypoxia. Using stepwise linear regression, we tested the hypothesis that exacerbated respiratory alkalosis, as a result of a brisk ventilatory response, sluggish renal compensation in acute hypoxia and dysregulation of cerebral perfusion predict AMS severity. We assessed the Lake Louise score (LLS, an index of AMS severity), fluid balance, ventilation, venous pH, bicarbonate, sodium and creatinine concentrations, body weight, urinary pH and cerebral blood flow [internal carotid artery (ICA) and vertebral artery (VA) blood flow and diameter], in 27 healthy individuals (13 women) throughout 10 h exposures to normobaric normoxia (fraction of inspired O = 0.21) and normobaric hypoxia (fraction of inspired O = 0.117, simulated 5000 m) in a randomized, single-blinded manner. In comparison to normoxia, hypoxia increased the LLS, ventilation, venous and urinary pH, and blood flow and diameter in the ICA and VA, while venous concentrations of both bicarbonate and creatinine were decreased (P < 0.001 for all). There were significant correlations between AMS severity and the rates of change in blood pH, sodium concentration and VA diameter and more positive fluid balance (P < 0.05). Stepwise regression found increased blood pH [beta coefficient (β) = 0.589, P < 0.001] and VA diameter (β = 0.418, P = 0.008) to be significant predictors of AMS severity in our cohort [F(2, 20) = 16.1, R = 0.617, P < 0.001, n = 24], accounting for 62% of the variance in peak LLS. Using classic regression variable selection, our data implicate the degree of respiratory alkalosis and cerebrovascular dilatation in the early stages of AMS development.
本研究的核心问题是什么？急性高原病（AMS）的病理生理学涉及呼吸、肾脏和脑血管系统，目前仍知之甚少。在模拟海拔5000米时，这些系统的早期适应性变化与AMS风险有何关联？主要发现及其重要性是什么？血液碱中毒速率和脑动脉扩张可预测在暴露于模拟海拔5000米的最初10小时内AMS的严重程度。肾脏对因快速呼吸反应导致的呼吸性碱中毒的代谢代偿缓慢，以及过度的脑血管扩张可能参与了AMS的早期发展。
急性高原病（AMS）复杂的病理生理学仍知之甚少，可能涉及呼吸、肾脏和脑血管系统对缺氧的适应不良反应。我们采用逐步线性回归，检验了以下假设：快速通气反应导致的呼吸性碱中毒加剧、急性缺氧时肾脏代偿迟缓以及脑灌注失调可预测AMS的严重程度。我们以随机、单盲的方式，在27名健康个体（13名女性）暴露于常压低氧（吸入氧分数=0.21）和常压低氧（吸入氧分数=0.117，模拟海拔5000米）的10小时内，评估了路易斯湖评分（LLS，AMS严重程度指标）、液体平衡、通气、静脉血pH值、碳酸氢盐、钠和肌酐浓度、体重、尿pH值以及脑血流量[颈内动脉（ICA）和椎动脉（VA）血流量及直径]。与常氧相比，低氧状态下LLS、通气、静脉血和尿pH值、ICA和VA的血流量及直径均增加，而静脉血中碳酸氢盐和肌酐浓度均降低（所有P<0.001）。AMS严重程度与血pH值、钠浓度和VA直径的变化率以及更正向的液体平衡之间存在显著相关性（P<0.05）。逐步回归分析发现，血pH值升高[β系数（β）=0.589，P<0.001]和VA直径增大（β=0.418，P=0.008）是我们队列中AMS严重程度的显著预测因素[F(2, 20)=16.1，R=0.617，P<0.001，n=24]，占峰值LLS方差的62%。使用经典回归变量选择方法，我们的数据表明呼吸性碱中毒程度和脑血管扩张在AMS发展的早期阶段起作用。
