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Front. Physiol. | doi: 10.3389/fphys.2018.00130

The influence of CO2 and exercise on hypobaric hypoxia induced pulmonary edema in rats

 Ryan L. Sheppard1, 2*,  Joshua M. Swift2,  Aaron Hall2 and Richard T. Mahon2
  • 1Naval Submarine Medical Research Laboratory, United States
  • 2Operational and Undersea Medicine, Naval Medical Research Center, United States

Individuals with a known susceptibility to high altitude pulmonary edema (HAPE) demonstrate a reduced ventilation response and increased pulmonary vasoconstriction when exposed to hypoxia. It is unknown whether reduced sensitivity to hypercapnia is correlated with increased incidence and/or severity of HAPE, and while acute exercise at altitude is known to exacerbate symptoms the effect of exercise training on HAPE susceptibility is unclear.
Purpose: To determine if chronic intermittent hypercapnia and exercise increases the incidence of HAPE in rats.
Methods: Male Wistar rats were randomized to sedentary (sed-air), CO2 (sed-CO2,) exercise (ex-air), or exercise + CO2 (ex-CO2) groups. CO2 (3.5%) and treadmill exercise (15m/min, 10% grade) were conducted on a metabolic treadmill, 1hr/day for 4 weeks. Vascular reactivity to CO2 was assessed after the training period by rheoencephalography. Following the training period, animals were exposed to hypobaric hypoxia (HH) equivalent to 25,000ft for 24 hrs. Pulmonary injury was assessed by wet/dry weight ratio, lung vascular permeability, bronchoalveolar lavage (BAL), and histology.
Results: HH increased lung wet/dry ratio (HH 5.51±0.29 vs. sham 4.80±0.11, P < 0.05), lung permeability (556±84u/L vs. 192±29u/L, P < 0.001), and BAL protein (221±33µg/ml vs. 114±13 µg/ml, P < 0.001), white blood cell (1.16±0.26 vs. 0.66±0.06, P < 0.05), and platelet (16.4±2.3, vs. 6.0±0.5, P < 0.001) counts in comparison to normobaric normoxia. Vascular reactivity was suppressed by exercise (-53% vs sham, P < 0.05) and exercise+CO2 (-71% vs sham, P < 0.05). However, neither exercise nor intermittent hypercapnia altered HH-induced changes in lung wet/dry weight, BAL protein and cellular infiltration, or pulmonary histology.
Conclusion: Exercise training attenuates vascular reactivity to CO2 in rats but neither exercise training nor chronic intermittent hypercapnia affect HH- induced pulmonary edema.

Keywords: HAPE, Hypercapnia, Exercise, hypoxia, chemoreflex

Received: 24 Oct 2017; Accepted: 08 Feb 2018.

Edited by:

RODRIGO DEL RIO, Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Chile

Reviewed by:

Marli C. Martins-Pinge, Universidade Estadual de Londrina, Brazil
Beth J. Allison, Hudson Institute of Medical Research, Australia  

Copyright: © 2018 Sheppard, Swift, Hall and Mahon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ryan L. Sheppard, Naval Submarine Medical Research Laboratory, Groton, United States,