Physiological and genomic consequences of intermittent hypoxia - Selected contribution: Pulmonary hypertension in mice following intermittent hypoxia
Physiological and genomic consequences of intermittent hypoxia - Selected contribution: Pulmonary hypertension in mice following intermittent hypoxia
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DOI：
10.1152/jappl.2001.90.6.2502
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发表时间：
2001-06-01
影响因子：
3.3
通讯作者：
Fagan, KA
中科院分区：
文献类型：
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作者：
Fagan, KA
睡眠呼吸暂停（间歇性缺氧伴或不伴高碳酸血症）与全身性高血压和心血管疾病死亡率增加有关，但与肺动脉高压的关系尚不确定。先前对肺动脉高压大鼠间歇性缺氧（IH）的研究利用了相对较长时间的缺氧。最近的研究利用短时间的缺氧有矛盾的报告右心室（RV）肥厚。此外，许多研究还没有测量肺血流动力学来评估体内肺动脉高压的严重程度。考虑到基因工程小鼠的不断增加以及建立IH诱导的肺动脉高压啮齿动物模型的必要性，我们研究了IH（2分钟周期，10%和21% o - 2,8 h/天，4周）对野生型小鼠的影响，将肺高压的体内测量与RV质量和肺血管重构相关联。与正常缺氧（29.5 +/- 0.6）相比，IH后左室收缩压（36 +/- 0.9 mmHg）升高，但低于持续缺氧（44.2 +/- 3.4）。右心室质量[左心室与（左室间隔）之比]与血压测量相关（IH = 0.27 +/- 0.02，常氧= 0.22 +/- 0.01，持续缺氧= 0.34 +/- 0.01）。IH和持续缺氧后，红细胞压积也升高（56 +/- 1.6和54 +/- 1.1 vs. 44.3 +/- 0.5%）。在IH和持续缺氧后发现了远端肺循环新肌肉化的证据。我们得出结论，小鼠在IH后出现肺动脉高压，代表了一种可能的肺高压动物模型，以响应睡眠呼吸暂停的重复缺氧-再氧合。
Sleep apnea (intermittent periods of hypoxia with or without hypercapnia) is associated with systemic hypertension and increased mortality from cardiovascular disease, but the relationship to pulmonary hypertension is uncertain. Previous studies on intermittent hypoxia (IH) in rats that demonstrated pulmonary hypertension utilized relatively long periods of hypoxia. Recent studies that utilized brief periods of hypoxia have conflicting reports of right ventricular (RV) hypertrophy. In addition, many studies have not measured pulmonary hemodynamics to asses the severity of pulmonary hypertension in vivo. Given the increasing availability of genetically engineered mice and the need to establish a rodent model of IH-induced pulmonary hypertension, we studied the effect of IH (2-min cycles of 10% and 21% O-2, 8 h/day, 4 wk) on wild-type mice, correlating in vivo measurements of pulmonary hypertension with RV mass and pulmonary vascular remodeling. RV systolic pressure was increased after IH (36 +/- 0.9 mmHg) compared with normoxia (29.5 +/- 0.6) but was lower than continuous hypoxia (44.2 +/- 3.4). RV mass [RV-to-( left ventricle plus septum) ratio] correlated with pressure measurements (IH = 0.27 +/- 0.02, normoxia = 0.22 +/- 0.01, and continuous hypoxia = 0.34 +/- 0.01). Hematocrits were also elevated after IH and continuous hypoxia (56 +/- 1.6 and 54 +/- 1.1 vs. 44.3 +/- 0.5%). Evidence of neomuscularization of the distal pulmonary circulation was found after IH and continuous hypoxia. We conclude that mice develop pulmonary hypertension following IH, representing a possible animal model of pulmonary hypertension in response to the repetitive hypoxia-reoxygenation of sleep apnea.