Calendar | For Your Patients | PHA Main Site | Contact Us | About Us | Not a registered user? Sign up here.

Resource Library

High-Altitude Pulmonary Edema Susceptibility in Relation to Epigenetic Patterns of Pulmonary Distensibility and Arterial Fractal Network Design

R. Allen

J. M. Milstein

A. J. Moon-Grady

G. W. Raff

S. M. Black

Jeffrey Fineman

Stephen Bennett

Marlowe Eldridge

Reviews

  Sign in to add a review

0 comments
Leave a Comment

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 ).

METHODSPressure-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).

RESULTSFigure 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.

High-Altitude Pulmonary Edema Susceptibility in Relation to Epigenetic Patterns of Pulmonary Distens

REFERENCES:

  1. Eldridge MW, Podolsky A, Richardson RS, et al. Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema. J Appl Physiol 1996;81:911-921.
  2. Ghorishi Z, Milstein J, Poulain F, et al. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow. Am J Physiol Heart Circ Physiol 2007;292:H3006-H3018.