Berger Marc M, Hesse Christiane, Dehnert Christoph, Siedler Heike, Kleinbongard Petra, Bardenheuer Hubert J, Kelm Malte, Bärtsch Peter, Haefeli Walter E
Department of Internal Medicine VI (Clinical Pharmacology and Pharmacoepidemiology), University of Heidelberg, Germany.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):763-7. doi: 10.1164/rccm.200504-654OC. Epub 2005 Jun 9.
High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung.
We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature.
During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects.
Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02).
Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.
高原肺水肿（HAPE）的特征是肺血管过度收缩，且与肺中一氧化氮（NO）浓度降低有关。
我们假设易患高原肺水肿（HAPE-S）的个体在全身血管系统缺氧时，血管NO舒张途径也会出现功能障碍。
在常氧状态下（吸入氧分数（FI(O₂)）=0.21）以及4小时的常压缺氧状态下（FI(O₂)=0.12，相当于海拔4500米），分别通过前臂静脉阻塞体积描记法测量了9名HAPE-S受试者和9名抗高原肺水肿对照受试者对动脉内注入乙酰胆碱（ACh）和硝普钠的内皮依赖性和非内皮依赖性血管舒张反应。
在缺氧状态下，对照受试者的肺动脉收缩压从22±3毫米汞柱升至33±6毫米汞柱（p<0.001），而HAPE-S受试者从25±4毫米汞柱升至50±9毫米汞柱（p<0.001）。尽管两组在常氧状态下反应相似，但在缺氧状态下，HAPE-S受试者中ACh诱导的前臂血流变化显著降低（p=0.01），而对照受试者中未出现此情况。缺氧状态下对ACh注入的血管反应减弱与肺动脉收缩压升高呈负相关（p=0.04），且在HAPE-S受试者中，血浆亚硝酸盐降低与ACh诱导的血管舒张减弱相关（p=0.02）。
由于NO生物利用度降低，缺氧显著损害了HAPE-S受试者体循环中的血管内皮功能。NO途径的损害可能导致缺氧性肺血管收缩增强，这是HAPE发病机制的核心。
