title: Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation.
abstract: High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2= 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV). Why HPV is uneven in HAPE-susceptible individuals is unknown but may arise from regionally heterogeneous ventilation resulting in an uneven stimulus to HPV. We tested the hypothesis that ventilation is more heterogeneous in HAPE-susceptible subjects (n= 6) compared with HAPE-resistant controls (n= 7). MRI specific ventilation imaging (SVI) was used to measure regional specific ventilation and the relative dispersion (SD/mean) of SVI used to quantify baseline heterogeneity. Ventilation heterogeneity from conductive and respiratory airways was measured in normoxia and hypoxia (O2= 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes Scondand Sacin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls [susceptible = 1.33 ± 0.67 (SD), resistant = 2.36 ± 0.98,P= 0.05], and Sacintended to be more uniform (susceptible = 0.085 ± 0.009, resistant = 0.113 ± 0.030,P= 0.07). Scondwas not significantly different between groups (susceptible = 0.019 ± 0.007, resistant = 0.020 ± 0.004,P= 0.67). Sacinand Sconddid not change significantly in hypoxia (P= 0.56 and 0.19, respectively). In conclusion, ventilation heterogeneity does not change with short-term hypoxia irrespective of HAPE susceptibility, and lesser rather than greater ventilation heterogeneity is observed in HAPE-susceptible subjects. This suggests that the basis for uneven HPV in HAPE involves vascular phenomena.NEW & NOTEWORTHYUneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.
authors.affiliation: Department of Anesthesiology, University of Washington, Seattle, Washington.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Patz
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Rui C
authors.identifier: http://orcid.org/0000-0002-8885-8671
authors.initials: RC
authors.lastname: Sá
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Chantal
authors.initials: C
authors.lastname: Darquenne
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Ann R
authors.initials: AR
authors.lastname: Elliott
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Amran K
authors.initials: AK
authors.lastname: Asadi
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California; and.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Theilmann
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California; and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Dubowitz
authors.affiliation: Medical Service, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California.|Department of Radiology, University of California, San Diego, La Jolla, California; and.
authors.forename: G Kim
authors.initials: GK
authors.lastname: Prisk
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; shopkins@ucsd.edu.|Department of Radiology, University of California, San Diego, La Jolla, California; and.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hopkins
mesh_terms: D000328:Adult; D000531:Altitude; D004198:Disease Susceptibility / Q000503:physiopathology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011654:Pulmonary Edema / Q000209:etiology* / Q000503:physiopathology*; D012123:Pulmonary Ventilation / Q000502:physiology*; D012119:Respiration; D014661:Vasoconstriction / Q000502:physiology; D055815:Young Adult
keywords: high-altitude illness; high-altitude pulmonary edema; multiple-breath washout; proton magnetic resonance imaging; specific ventilation imaging