Effects of Hypercapnic Exercise on the Severity of Hypobaric Hypoxia Induced Pulmonary Injury

Abstract

Humans operating at altitude are susceptible to high altitude pulmonary edema (HAPE), a form of altitude sickness resulting from exaggerated pulmonary vasoconstriction and increased pulmonary capillary pressures. Naval Special Warfare (NSW) operators appear to be more susceptible than other military personnel. We hypothesize that this is due to a unique underwater training and selection process which leads to a suppression of respiratory drive when exposed to hypobaric hypoxia. This hypothesis is being tested in a rodent model using hypercapnic exercise and simulated altitude. Male Wistar rats are exposed to 3.5% CO2 with and without moderate treadmill exercise (15m/min, 5%), 1hr/day, 5days/week for 5 weeks. Vascular reactivity to bolus CO2 (12%) was then assessed via rheoencephalography and laser Dopplar flow. Hypoxic respiration (10‐18% O2) is monitored in modified plethysmography chambers, and animals are exposed to hypobaric hypoxia at altitude equivalents ranging from 18,000‐30,000ft for 5‐24 hours. End points include respiratory rate and volume, lung wet/dry ratios, BAL protein and cell counts, arterial blood gases, pulmonary histology, and gene expression of HIF1α, IL‐6, and TNFα. Cerebral vascular reactivity to bolus CO2 is reduced with exercise alone (‐53% of control), CO2 alone (‐46% of control), and exercise+CO2 (‐62% of control). Right lung wet/dry weight ratios are not significantly increased by altitude exposure under any of the conditions tested. Severe dehydration, up to 12% loss of body weight in 24 hours, is a significant impediment that we are unable to adequately address and which we believe is a fundamental problem with rodent HAPE models. Analysis of respiration, BAL fluid, blood gases, lung pathology and gene expression is ongoing.