Physiological aspects of high-altitude pulmonary edema

Abstract

High-altitude pulmonary edema (HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure (PAP) preceding edema formation is the crucial pathophysiological factor because drugs that lower PAP prevent HAPE. Measurements of nitric oxide (NO) in exhaled air, of nitrites and nitrates in bronchoalveolar lavage (BAL) fluid, and forearm NO-dependent endothelial function all point to a reduced NO availability in hypoxia as a major cause of the excessive hypoxic PAP rise in HAPE-susceptible individuals. Studies using right heart catheterization or BAL in incipient HAPE have demonstrated that edema is caused by an increased microvascular hydrostatic pressure in the presence of normal left atrial pressure, resulting in leakage of large-molecular-weight proteins and erythrocytes across the alveolarcapillary barrier in the absence of any evidence of inflammation. These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term "stress failure." Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. This compelling but as yet unproven mechanism predicts that edema occurs in areas of high blood flow due to lesser vasoconstriction. The combination of high flow at higher pressure results in pressures, which exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance. pulmonary artery pressure; hypoxic pulmonary vasoconstriction; nitric oxide; inflammation; alveolar fluid clearance; pathophysiology; review CLINICAL PICTUREHigh-altitude pulmonary edema (HAPE) is noncardiogenic pulmonary edema that usually occurs at altitudes above 3,000 m in rapidly ascending nonacclimatized individuals within the first 2-5 days after arrival. It may also occur in high-altitude dwellers who return from sojourns at low altitude. The first medical description of HAPE was published in Peru and recognized the latter form, also called reentry HAPE, as a pulmonary edema associated with electrographic signs of right ventricular overload (67). The first cases of HAPE in unacclimatized lowlanders climbing to high altitude were reported from the Rocky Mountains (53). The two forms very probably share the same pathophysiology.The reader is referred to other reviews (9,41,96,97) for an extensive presentation of the clinical picture. In this review, we point out some particular characteristics that might elucidate the underlying pathophysiology and are revealed by classical and newly evolving pathophysiological concepts.The prevalence of HAPE depends on the degree of susceptibility, the rate of ascent, and the final altitude. At an altitude of 4,500 m, the prevalence may ...

Acute high-altitude sickness

“…The pathophysiology of HAPE has been reviewed extensively elsewhere [61]. Since its recognition in the 1960s, a number of pathophysiological mechanisms have been proposed.…”

Reduced lung uptake of Iodine‐123 metaiodobenzylguanidine in high‐altitude pulmonary oedema

“…The pathogenesis of HAPE is considered an altered permeability of alveolar-capillary barrier due to enhanced hypoxic pulmonary vasoconstriction and high capillary pressure [17][18][19][20][21] . In addition, several clinical studies suggest that individuals susceptible to HAPE have dysfunction in vascular endothelial nitric oxide (NO) vasodilator pathway during hypoxia 24,25 .…”

“…HAPE occurs in individuals who fail to acclimatize to altitudes above 2,500 m 15,16 . Although the mechanism of HAPE remains unknown, increases in pulmonary vascular pressure and/or microvascular permeability have been implicated in the pathophysiology of HAPE [17][18][19][20] . Thus, functional changes in the pulmonary vascular endothelium might be associated with the development of HAPE.…”

Can sildenafil improve physical performance at altitude? Current scientific evidence

“…14---16 VO 2max tends to diminish in direct proportion to the decrease in CaO 2 , which occurs as hypoxia increases. 17,18 Exercise exacerbates CaO 2 reduction due to the lower uptake of O 2 during gas exchanging in the lungs, 1,19 which may increase the risk of pulmonary edema, 11,20 especially in people predisposed to suffer this complications associated to rapid ascent. 21 Considering that the increase in PAP could be an important factor limiting performance during exercise in hypoxia, 22 sildenafil has been proposed as a potential ergogenic aid for physical activity in hypoxic conditions due to its possible benefits for athletic performance, and has been widely used.…”