The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats
Introduction: 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 a...
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Frontiers Media S.A.
2018-02-01
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Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00130/full |
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author | Ryan L. Sheppard Ryan L. Sheppard Joshua M. Swift Aaron Hall Richard T. Mahon |
author_facet | Ryan L. Sheppard Ryan L. Sheppard Joshua M. Swift Aaron Hall Richard T. Mahon |
author_sort | Ryan L. Sheppard |
collection | DOAJ |
description | Introduction: 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 (15 m/min, 10% grade) were conducted on a metabolic treadmill, 1 h/day for 4 weeks. Vascular reactivity to CO2 was assessed after the training period by rheoencephalography (REG). Following the training period, animals were exposed to hypobaric hypoxia (HH) equivalent to 25,000 ft for 24 h. 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 ± 84 u/L vs. 192 ± 29 u/L, P < 0.001), and BAL protein (221 ± 33 μg/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. |
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spelling | doaj.art-b498b6ee97cf4ecb9169621d6da142212022-12-22T00:32:40ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-02-01910.3389/fphys.2018.00130323607The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in RatsRyan L. Sheppard0Ryan L. Sheppard1Joshua M. Swift2Aaron Hall3Richard T. Mahon4Department of Submarine Medicine and Survival Systems Groton, Naval Submarine Medical Research Laboratory, Groton, CT, United StatesDepartment of Undersea Medicine, Walter Reed Army Institute of Research and Naval Medical Research Center, Silver Spring, MD, United StatesDepartment of Undersea Medicine, Walter Reed Army Institute of Research and Naval Medical Research Center, Silver Spring, MD, United StatesDepartment of Undersea Medicine, Walter Reed Army Institute of Research and Naval Medical Research Center, Silver Spring, MD, United StatesDepartment of Undersea Medicine, Walter Reed Army Institute of Research and Naval Medical Research Center, Silver Spring, MD, United StatesIntroduction: 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 (15 m/min, 10% grade) were conducted on a metabolic treadmill, 1 h/day for 4 weeks. Vascular reactivity to CO2 was assessed after the training period by rheoencephalography (REG). Following the training period, animals were exposed to hypobaric hypoxia (HH) equivalent to 25,000 ft for 24 h. 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 ± 84 u/L vs. 192 ± 29 u/L, P < 0.001), and BAL protein (221 ± 33 μg/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.http://journal.frontiersin.org/article/10.3389/fphys.2018.00130/fullvascular reactivityHAPEchemoreflexhypercapniaexercise |
spellingShingle | Ryan L. Sheppard Ryan L. Sheppard Joshua M. Swift Aaron Hall Richard T. Mahon The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats Frontiers in Physiology vascular reactivity HAPE chemoreflex hypercapnia exercise |
title | The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats |
title_full | The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats |
title_fullStr | The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats |
title_full_unstemmed | The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats |
title_short | The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats |
title_sort | influence of co2 and exercise on hypobaric hypoxia induced pulmonary edema in rats |
topic | vascular reactivity HAPE chemoreflex hypercapnia exercise |
url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00130/full |
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