Conference: 2008 International PHA Conference and Scientific Sessions
Release Date: 06.20.2008
Presentation Type: Abstracts
Allen R.P. 1, Milstein J.M. 1, Moon-Grady A.J. 1,2, Raff G.W. 1,2, Black S.M. 3, Fineman J.R. 2, Bennett S.H. 1, Eldridge M.W. 4
1. University of California, Davis, CA, USA
2. University of California, San Francisco, CA, USA
3. Medical College of Georgia, Augusta, GA, USA
4. Medical College of Wisconsin, Milwaukee, WI, USA
BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension upon rapid ascent to altitude by an unknown mechanism. We hypothesized that HAPE-susceptible (HAPE-S) individuals possess a more reactive arterial network organization than Control subjects (CON), characterized mechanically by smaller arterial distensibility a (mmHg-1), with a greater tendency to remodel to a fetal phenotype of arterial network organization (Phenotype: Fetal , Adult ).
METHODS: Pressure-flow relationships of CON and HAPE-S subjects(1) were interpreted on the basis of a fractal resistance under the principle of minimum-work, to yield distensibility a (mmHg-1) and the phenotype of arterial network organization(2) under conditions of sea-level (SL), altitude (ALT), nomoxia (N) and hypoxia (H).
RESULTS: Figure 1 indicates HAPE-S and CON subjects possess significantly smaller a, which respond differently to H (…). Altitude remodeled the pulmonary circulation to a fetal phenotype in both CON and HAPE-S subjects, yielding a greater shear stress load on generation 19 .0050 cm vessels, where the threshold of acute shear stress injury in large arteries is dyne cm-2.
COMMENTS AND CONCLUSIONS: Greater reactivity of HAPE-S at ALT is explained by proclivity to mechanically remodel to a fetal-like configuration, independent of hypoxia, and with significantly smaller a dependent upon H. Remodeling at ALT to a fetal phenotype may induce focal endothelial injury secondary to exercise exceeding injury thresholds. Differences between HAPE-S and CON may be epigenetic secondary to fetal/postnatal experience with pulmonary hypertension.