Masschelein Evi, Van Thienen Ruud, Thomis Martine, Hespel Peter
1Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, BELGIUM; and 2Physical Activity, Sports and Health Research Group, Department of Kinesiology, KU Leuven, Leuven, BELGIUM.
Med Sci Sports Exerc. 2015 Jan;47(1):74-81. doi: 10.1249/MSS.0000000000000386.
Physiological responses to hypoxia vary between individuals, and genetic factors are conceivably involved. Using a monozygotic twin design, we investigated the role of genetic factors in physiological responses to acute hypoxia.
Thirteen pairs of monozygotic twin brothers participated in two experimental sessions in a normobaric hypoxic facility with a 2-wk interval. In one session, fraction of inspired O2 (FiO2) was gradually reduced to 10.7% (approximately 5300 m altitude) over 5 h. During the next 3 h at 10.7%, FiO2 subjects performed a 20-min submaximal exercise bout (EXSUB, 1.2 W·kg) and a maximal incremental exercise test (EXMAX). An identical control experiment was done in normoxia. Cardiorespiratory measurements were continuously performed, and 8-h urine output was collected.
Compared with normoxia, hypoxia decreased (P < 0.05) arterial O2 saturation (%SpO2) at rest (-22%) and during exercise (-28%). Furthermore, V˙O2max (-39%), HRmax (HR, -8%), maximal pulmonary ventilation (V˙Emax, -11%), and urinary norepinephrine excretion (-31%) were reduced (P < 0.05) whereas HR at rest (25%) and during EXSUB (16%) and V˙E at rest (38%) and during EXSUB (70%) were increased (P < 0.05). However, hypoxia-induced changes (Δ) were not randomly distributed between subjects. Between-pair variance was substantially larger than within-pair variance (P < 0.05) for Δ%SpO2 at rest (approximately threefold) and during exercise (approximately fourfold), ΔV˙O2max (approximately fourfold), ΔHR during exercise (approximately seven- to eightfold), hypoxic ventilatory response (approximately sixfold), and Δ urinary norepinephrine output (approximately threefold). Incidence of acute mountain sickness (AMS) also yielded significant twin similarity (P < 0.05). AMS subjects showed approximately 50% greater drop in urinary norepinephrine and lower hypoxic ventilator response than AMS individuals.
Our data suggest that genetic factors regulate cardiorespiratory responses, exercise tolerance, and pathogenesis of AMS symptoms in acute severe hypoxia. Hypoxia-induced sympathetic downregulation was associated with AMS.
个体对低氧的生理反应存在差异，遗传因素可能与之相关。我们采用同卵双胞胎设计，研究遗传因素在急性低氧生理反应中的作用。
13对同卵双胞胎兄弟参与了在常压低氧设施中进行的两个实验阶段，间隔2周。在一个阶段中，吸入氧分数（FiO2）在5小时内逐渐降至10.7%（相当于海拔约5300米）。在接下来的3小时保持在10.7% FiO2时，受试者进行了20分钟的次最大运动试验（EXSUB，1.2 W·kg）和最大递增运动试验（EXMAX）。在常氧环境下进行了相同的对照实验。持续进行心肺测量，并收集8小时尿量。
与常氧相比，低氧使静息时（-22%）和运动时（-28%）的动脉血氧饱和度（%SpO2）降低（P < 0.05）。此外，最大摄氧量（V˙O2max，-39%）、最大心率（HRmax，HR，-8%）、最大肺通气量（V˙Emax，-11%）和尿去甲肾上腺素排泄量（-31%）降低（P < 0.05），而静息时（25%）和EXSUB期间（16%）的心率以及静息时（38%）和EXSUB期间（70%）的每分通气量（V˙E）增加（P < 0.05）。然而，低氧诱导的变化（Δ）在受试者之间并非随机分布。对于静息时（约三倍）和运动时（约四倍）的Δ%SpO2、ΔV˙O2max（约四倍）、运动时的ΔHR（约七至八倍）、低氧通气反应（约六倍）以及Δ尿去甲肾上腺素输出量（约三倍），双胞胎之间的方差显著大于双胞胎内部的方差（P < 0.05）。急性高山病（AMS）的发生率也显示出显著的双胞胎相似性（P < 0.05）。AMS受试者的尿去甲肾上腺素下降幅度比非AMS个体大50%左右，低氧通气反应更低。
我们的数据表明，遗传因素调节急性严重低氧时的心肺反应、运动耐力和AMS症状的发病机制。低氧诱导的交感神经下调与AMS有关。
