Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation

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 (O-2 = 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 (O-2 = 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes S-cond and S-acin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPEresistant controls [susceptible = 1.33 +/- 0.67 (SD), resistant = 2.36 +/- 0.98, P = 0.05], and Sacin tended to be more uniform (susceptible = 0.085 +/- 0.009, resistant = 0.113 +/- 0.030, P = 0.07). Scond was not significantly different between groups (susceptible = 0.019 +/- 0.007, resistant = 0.020 +/- 0.004, P = 0.67). S-acin and S-cond did 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 & NOTEWORTHY Uneven 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 HAPEresistant subjects. Contrary to our hypothesis, ventilation heterogene-ity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.