Abnormal Circulatory Responses to High Altitude in Subjects with a Previous History of High-Altitude Pulmonary Edema

Abstract

In five men with a history of susceptibility to high-altitude pulmonary edema (HAPE), hemodynamics and pulmonary gas exchange were measured at sea level, and again 24 hours following ascent to an altitude of 3,100 m. At sea level, all findings were essentially normal including a mean pulmonary arterial pressure [See Equation in PDF File] of 13.8 ± 1.9 mm Hg. None of the subjects developed clinically detectable pulmonary edema at altitude. Wedge pressures and cardiac output remained normal. [See Equation in PDF File] increased remarkably, being 38.8 ± 10.3 mm Hg at rest and 53.2 ± 11.6 mm Hg during moderate exercise. Acute relief of hypoxia only partially relieved this pulmonary hypertension. Arterial blood gases were normal at sea level. In spite of hyperventilation at altitude, arterial O 2 pressure was only 50.8 ± 6.1 torr at rest and fell to 41.4 ± 3.3 torr during exercise due to a widening of the alveolar-arterial O 2 pressure difference to 28.0 ± 6.8 torr. Hence, these men susceptible to HAPE developed excessive pulmonary hypertension and impaired pulmonary O 2 exchange without detectable pulmonary edema following ascent to high altitude. The increase in pulmonary vascular resistance is only partially explained by hypoxic pulmonary vasoconstriction.

High-altitude pulmonary hypertension: a pathophysiological entity to different diseases

“…In lowlanders susceptible to HAPE, mean PAP was on average 38 mmHg with a range of 31-51 mmHg [17]. These results are consistent with an earlier report in five HAPE-susceptible subjects that showed a mean PAP of 39 mmHg (range 22-47 mmHg) 24 h after arrival at 3,100 m [19]. However, as shown in figure 1 there is a considerable overlap between the mean PAP values reported in HAPE-resistant and -susceptible individuals at high altitude.…”

“…The figure shows that for the pooled data (n=47), there is a significant correlation of the second order between haemoglobin and PAP (r=0.64, pv0.001), but that, as previously reported [20,53], this relationship is lost in patients with CMS (r=0.25, p=0.62). Furthermore, the figure illustrates that at a comparable mean PAP of y40 mmHg (mean ¡ SD: Han Chinese 40 ¡ 11 versus South Americans 45 ¡ 18, p=0.87), haemoglobin concentration is lower in Han Chinese (mean ¡ SD 20.3 ¡ 1.9 g?dL -1 , range [17][18][19][20][21][22] than in the natives of the Andes (mean ¡ SD 24.6 ¡ 2.1 g?dL -1 , range 20-27; pv0.01, MannWhitney U-test). The haemoglobin concentration in healthy individuals in Lhasa (3,600 m) is y17 g?dL -1 [14] and in La Oroya in Peru (3,690 m) y18 g?dL -1 [18].…”

“…In residents of high altitude living in Tibet [4] and in the central Andes of Peru [18], PAP was measured at 3658 m, 3690 m and 4260 m, respectively. Open squares (high-altitude pulmonary oedema (HAPE) prone) show mean PAP values obtained at altitudes between 2600-4559 m in nonacclimatised HAPE-susceptible subjects without HAPE (No HAPE; 3100-4559 m) [17,19], with HAPE [17] in an early stage (Early HAPE; 4559 m), and with HAPE in an advanced stage (Adv HAPE; 2600-4331 m). In the latter group, mean PAP was measured at hospital admission.…”

“Into Thin Air” and the Genetics of Complex Traits

“…3 Those with higher pulmonary artery pressure at rest or an exaggerated response to hypoxia or exercise are considered to be at higher risk. 4 Therefore, one could postulate that genetic variants that affect pulmonary arterial pressure could serve as susceptibility alleles for HAPE. The article by Droma et al 1 suggests that variants of the endothelial nitric oxide synthase gene (NOS3) could affect susceptibility to HAPE.…”

“…As a result of these limitations, 3 criteria need to be met before the results of genetic association studies can be taken literally: namely, adequate sample size, replication, and functional data. Until these criteria are met, the results of genetic association studies, including the results of Droma et al, 4 should be considered provocative but preliminary. Finally, given the central role of exaggerated pulmonary vasoactive response to hypoxemia in patients with HAPE, studies of uncommon genetic disorders, such as primary pulmonary hypertension, could provide additional information.…”