Dept of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Eur Respir J. 2021 Oct 7;58(4). doi: 10.1183/13993003.00352-2021. Print 2021 Oct.
Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations oxidative stress.
Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidant -butyl hydroperoxide (TBHP).
In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength.
IH and OSA do not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.
阻塞性睡眠呼吸暂停（OSA）患者存在血液流变学改变，经持续气道正压通气（CPAP）治疗后可逆转，这种改变可能与间歇性低氧（IH）引起的氧化应激有关。本研究旨在探讨 IH 是否会引起血液流变学改变和氧化应激。
Wistar 大鼠分别暴露于常氧（n=7）或 IH（n=8）环境中 14 天。23 例中重度 OSA 患者分别在基线、随机分为夜间吸氧 2 周组（n=13）和不治疗组（n=10）以及 CPAP 治疗 1 个月后（n=17）三个时间点进行评估。另外，选择 13 例无 OSA 的健康对照者进行基线和匹配时间点的随访评估。检测血液流变学参数（红细胞压积、全血黏度、血浆黏度（仅大鼠）、红细胞聚集和变形性（仅人类））和氧化还原平衡（超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶、蛋白氧化（晚期氧化蛋白产物（AOPP））和脂质过氧化（丙二醛（MDA）））。在人类参与者中，我们还使用氧化剂叔丁基过氧化氢（TBHP）测试了红细胞对活性氧（ROS）的血液流变学敏感性。
在大鼠中，IH 通过增加红细胞压积增加全血黏度，而不改变红细胞的血液流变学特性。IH 还降低了 SOD 活性并增加了 AOPP。在人类中，患者和对照组的基线血液流变学特性相似，吸氧和 CPAP 治疗后特性没有改变，除了吸氧治疗后红细胞变形性降低。氧化还原平衡在患者和对照组之间相似。在基线时，TBHP 诱导患者红细胞变形性的降低更为明显，而 CPAP 降低了 TBHP 诱导的聚集强度的增加。
IH 和 OSA 尽管存在氧化应激或对 ROS 更敏感，但均不会引起血液流变学改变。
