Moya E A, Yu J J, Brown S, Gu W, Lawrence E S, Carlson R, Brandes A, Wegeng W, Amann K, McIntosh S E, Powell F L, Simonson T S
Division of Pulmonary, Critical Care, Sleep Medicine, and Physiology, Department of Medicine, University of California San Diego, La Jolla, CA, United States.
Department of Anesthesiology, Loyola University Medical Center, Maywood, IL, United States.
Front Physiol. 2024 May 9;15:1334874. doi: 10.3389/fphys.2024.1334874. eCollection 2024.
High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia.
We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO (PetCO) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO on ventilation and heart rate by calculating the differences of isocapnic poikilocapnic hypoxic conditions (Δ /ΔPetCO and ΔHR/ΔPetCO, respectively).
Male Tibetans had lower [Hb] compared to Han Chinese males ( < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group ( < 0.03), and the heart rate response to CO in hypoxia was lower in Tibetans relative to Han Chinese ( < 0.01).
These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.
高海拔人群表现出独特的细胞、呼吸和心血管表型,与具有海平面祖先的人群相比,其中一些表型在缺氧条件下具有适应性优势。在有高海拔居住史的人群(如藏族)中进行的研究支持这样一种观点,即这些表型中的许多可能是由历代受到正向选择的基因组特征所塑造的。我们假设,即使在没有严重持续缺氧的情况下,在高海拔地区藏族中观察到的此类特征在居住在中等海拔的藏族中也会出现。
我们研究了具有高海拔祖先(藏族,17名女性;12名男性)和海平面祖先(汉族,6名女性;10名男性)的个体,他们都在海拔约1300米(约4327英尺)的地方生活了至少18个月。我们在终末潮气二氧化碳(PetCO)保持恒定(等碳酸血症)或随着低氧性过度通气而降低(变碳酸血症)的情况下,测量了血红蛋白浓度([Hb])、低氧通气反应(HVR)和低氧心率反应(HHRR)。我们还通过计算等碳酸血症和变碳酸血症低氧条件下的差异(分别为Δ /ΔPetCO和ΔHR/ΔPetCO)来量化二氧化碳对通气和心率的贡献。
与汉族男性相比,藏族男性的[Hb]较低(<0.05),这与来自这些人群在高海拔和海平面生活的个体的报告一致。两组的通气测量值(静息通气、HVR和PetCO)相似。在等碳酸血症期间,两组对低氧的心率反应相似;然而,在变碳酸血症中,藏族组的HHRR降低(<0.03),并且与汉族相比,藏族在低氧状态下对二氧化碳的心率反应较低(<0.01)。
这些结果表明,居住在中等海拔的藏族在缺氧情况下心脏反应减弱。因此,在居住在高海拔的藏族中观察到的表型中,只有一部分在居住在中等海拔的藏族中被观察到。虽然在中等海拔地区发现了对缺氧的心脏反应减弱,但对高海拔的其他生理适应的表现可能需要暴露于更严重的缺氧水平。