Brief Reports Intracardiac Shunting across a Patent Foramen Ovale May Exacerbate Hypoxemia in High-Altitude Pulmonary Edema Benjamin D. Levine, MD; Paul A. Grayburn, MD; Wyatt F. Voyles, MD; E. Richard Greene, PhD: Robert C. Roach; and Peter H. Hackett, MD Annals of Internal Medicine. 1991;114:569-570. Rapid ascent to altitude in susceptible persons may result in severe hypoxemia, pulmonary hypertension, and even pulmonary edema. This life-threatening syn- drome affects approximately i% of climbers who rap- idly ascend to more than 3000 m (1). The underlying mechanisms for this problem have yet to be determined. We used bubble contrast and Doppler echocardiography on 12 climbers at 4200 m on Mount McKinley. Alaska, to test the hypothesis that a patent foramen ovale may provide an avenue for right-to-left shunting during high- altitude-induced hypoxia and pulmonary hypertension, resulting in disproportionate hypoxemia and contributing to the development of high-altitude pulmonary edema. the right ventricular outflow tract at 35 mm Hg (PPA = 79 - 0-45 [acceleration time]) (2). Trieuspid regurgita- tion was present, with a peak velocity of 3.5 m/s, sug- gesting a right ventricular systolic pressure of 60 mm Hg (3). Contrast echocardiography with agitated saline revealed prominent right-to-left shunting of microbub- bles across the interatrial septum at rest (Figure I). Six months after returning to sea level, color-flow mapping and pulsed Doppler echocardiography were done while the climber was well. Pulmonary pressures were normal, and there was no evidence of right-to-left shunting. Contrast echocardiography also revealed right-to-left shunting during cough or Valsalva maneu- ver in one other patient with high-altitude pulmonary edema (two of two patients), one of two patients with acute mountain sickness but without pulmonary edema, and two of eight well-acclimatized climbers (/* - 0.15 by the Fisher exact test for comparison between right- to-left shunting in climbers with acute mountain sick- ness or high-altitude pulmonary edema and normal climbers). All studies were conducted at 4200 m, at the laboratory of the Denali Medical Research Project on Mount McKinley (4). Discussion Patient and Methods A 42-year-old woman who ascended rapidly to 4200 m developed severe high-altitude pulmonary edema manifested by dyspnea at rest, rales, and oxyhemoglo- bin desaturation (50%). She was evacuated to sea level where she remained for 4 days. She subsequently re- turned to 4200 m, but at a much slower rate of ascent, stopping at 2375 m for 1 week to acclimatize, and reaching 4200 m after 12 days. On arrival at 4200 m (440 torr), she felt well, although dry rales were detected in the right middle lobe and at the right base. Oxyhemo- globin saturation using finger pulse oximetry (model 503, Criticare Systems, Inc., Milwaukee, Wisconsin) was 86% (normal) at rest. Doppter echocardiography (Interspec XL, Interspec, Conshohocken, Pennsylvania) was done, and mean pulmonary artery pressure (/*PA) was estimated from the acceleration time (measured in milliseconds) of the pulsed Doppler spectral tracing of From the Universily of Texas Southwestern Medical Center and the Veterans Administration Medical Center. Dallas. Texas; The Lovelace Medical Foundation. Albuquerque. New Mexico; and the University of Alaska. Anchorage. Alaska. Pulmonary hypertension and hypoxemia are impor- tant clinical features of high-altitude pulmonary edema (1). High altitude induces alveolar hypoxia that may be worsened in these patients by relative hypoventilation (5). Pulmonary hypertension then results, largely from pulmonary arteriolar vasoconstriction secondary to al- veolar hypoxia, which has been shown to be more prominent in persons who are susceptible to high-alti- tude pulmonary edema than in normal control persons (6). Hypoxemia may be further exaggerated by an in- creased alveolar-arterial gradient for oxygen, which has been attributed to the development of interstitial and alveolar edema or ventilation-perfusion mismatching (7). In a study of pulmonary gas exchange during a sim- ulated climb of Mount Everest, Wagner and colleagues (7) showed marked ventilation-pertusion mismatching, with areas of lung that manifested ventilation-perfusion ratios near 0 (shunt) and hypoxemia that was not re- versed by breatbing 100% oxygen. They calculated right-to-left shunts on the order of 10% in most sub- jects, with one subject developing a shunt of almost 50% during exercise along with clinical signs of pulmo- nary edema. The authors hypothesized the development of pulmonary edema (and therefore intrapulmonary shunting) as the most likely cause of their experimental i April 1991 • Annals of Internal Medicine * Volume 114 • Number 7 569