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.
Highlights
Individuals with a known susceptibility to high altitude pulmonary edema (HAPE) demonstrate a reduced ventilation response and increased pulmonary vasoconstriction when exposed to hypoxia
Numerous studies have indicated that HAPE susceptible individuals have a reduced hypoxic ventilation response (HVR) accompanied by lower pO2 levels and greater hypoxic pulmonary vasoconstriction than non-HAPE sensitives (Hyers et al, 1979; Matsuzawa et al, 1989; Hohenhaus et al, 1995; Bartsch et al, 2002), though a reduced HVR does not appear necessary for HAPE to develop (Selland et al, 1993)
This study examines the effect of chronic intermittent CO2 exposure, with and without concomitant exercise training, on the development of hypobaric hypoxia (HH) induced pulmonary edema in a rat model
Summary
Individuals with a known susceptibility to high altitude pulmonary edema (HAPE) demonstrate a reduced ventilation response and increased pulmonary vasoconstriction when exposed to hypoxia. 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, including increased plasma norepinephrine and sympathetic tone (Duplain et al, 1999), elevated endothelin (Ali et al, 2012; Barker et al, 2016), and decreased levels of exhaled nitric oxide (Duplain et al, 2000; Busch et al, 2001) and nitric oxide metabolite concentrations in both the systemic circulation and bronchoalveolar lavage (BAL) fluid (Swenson et al, 2002; Berger et al, 2005; Bailey et al, 2010). The mechanism of reduced HVR is multifactorial, but blunted central and peripheral chemoreceptor sensitivity likely plays a central role (Albert and Swenson, 2014)
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