The Influence of CO2 and Exercise on Hypobaric Hypoxia Induced Pulmonary Edema in Rats

Abstract

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.

Computed tomography findings of asphyxial suicide by the inhalation of helium inside a plastic bag

“…However, hypoxia does not always induce lung edema. One of the mechanisms underlying hypoxia-induced lung edema is pulmonary vasoconstriction that occurs with prolonged exposure to hypoxia [5]. Pulmonary vascular pressures subsequently increase and can stress the delicate alveolar capillary barrier and induce mechanical stress failure.…”

“…Pulmonary vascular pressures subsequently increase and can stress the delicate alveolar capillary barrier and induce mechanical stress failure. This pulmonary vascular response likely has multiple driving mechanisms involving the sympathetic tone, elevated endothelin 1 levels, or decreased levels of exhaled nitric oxide [5]. These complicated mechanisms may result in differences in the susceptibility of lungs to hypoxia.…”

Protective Effect of Aerobic Exercise on the Nasal Mucosa of Rats Against the Histopathologic Changes in Cigarette Smoke Exposure

“…The study protocol was developed with reference to previous experimental animal studies that had investigated the effects of smoking and exercise. 11,12 Group 1 rats were exposed to the equivalent of smoke from 15 cigarettes in an isolated cigarette smoke cabin for 30 minutes twice a day, 5 days a week, for 3 months. Group 2 rats were exposed to cigarette smoke at the same rates as the smoking group and were also forced to run at an average speed of 18 m/min on a treadmill (4-path treadmill for rats) for approximately 40 minutes a day, 5 days a week, for 3 months.…”