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 HAPE-susceptible, with a history of HAPE, but not HAPE-resistant (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-susceptibles 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 to 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 indices Scond and Sacin, respectively. Contrary to our hypothesis, HAPE-susceptibles had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls (Susceptible=1.33±0.67, 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). Sacin and Scond did not change significantly in hypoxia (p=0.56, 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 the basis for uneven HPV in HAPE involves vascular phenomena.
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