Heterogeneous pulmonary blood flow in response to hypoxia: a risk factor for high altitude pulmonary edema?
High altitude pulmonary edema (HAPE) is a rapidly reversible hydrostatic edema that occurs in individuals who travel to high altitude. The difficulties associated with making physiologic measurements in humans who are ill or at high altitude, along with the idiosyncratic nature of the disease and lack of appropriate animal models, has meant that our understanding of the mechanism of HAPE is incomplete, despite considerable effort. Bronchoalveolar lavage studies at altitude in HAPE-susceptible subjects have shown that mechanical stress-related damage to the pulmonary blood gas barrier likely precedes the development of edema. Although HAPE-susceptible individuals have increased pulmonary arterial pressure in hypoxia, how this high pressure is transmitted to the capillaries has been uncertain. Using functional magnetic resonance imaging of pulmonary blood flow, we have been able to show that regional pulmonary blood flow in HAPE-susceptible subjects becomes more heterogeneous when they are exposed to normobaric hypoxia. This is not observed in individuals who have not had HAPE, providing novel data supporting earlier suggestions by Hultgren that uneven hypoxic pulmonary vasoconstriction is an important feature of those who develop HAPE. This brief review discusses how uneven hypoxic pulmonary vasoconstriction increases regional pulmonary capillary pressure leading to stress failure of pulmonary capillaries and HAPE. We hypothesize that, in addition to the well-documented increase in pulmonary vascular pressure in HAPE-susceptible individuals, increased perfusion heterogeneity in hypoxia results in lung regions that are vulnerable to increased mechanical stress.
Hopkins
Susan R
SR
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. shopkins@ucsd.edu
Levin
David L
DL
D000532:Altitude Sickness / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D004198:Disease Susceptibility; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008279:Magnetic Resonance Imaging / Q000379:methods; D010100:Oxygen / Q000097:blood; D011654:Pulmonary Edema / Q000097:blood / Q000503:physiopathology*; D012307:Risk Factors
D010100:Oxygen