Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α

American Journal of Physiology. Lung Cellular and Molecular Physiology
A Charlotte P SewingRobert P Jankov

Abstract

Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed in human infants with severe bronchopulmonary dysplasia. Inhalation of CO(2) (therapeutic hypercapnia) has been described to limit cytokine production and to have anti-inflammatory effects on the injured lung; we therefore hypothesized that therapeutic hypercapnia would prevent bleomycin-induced lung injury. Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or saline vehicle from postnatal days 1-14 while being continuously exposed to 5% CO(2) (Pa(CO(2)) elevated by 15-20 mmHg), 7% CO(2) (Pa(CO(2)) elevated by 35 mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%, CO(2), had significantly attenuated lung tissue macrophage influx and PHT, as evidenced by normalized pulmonary vascular resistance and right ventricular systolic function, decreased right ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. The level of CO(2) neither prevented increased tissue neutrophil influx nor led to improvements in decreased lung weight, septal thinning, impaired alveolarization, or decreased numbers of peripheral ...Continue Reading

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Citations

Jan 19, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Cassidy DelaneyEva Nozik-Grayck
Jan 18, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hartmut GrasemannRobert P Jankov
Jun 19, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mong Tieng EeRobert P Jankov
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Dec 30, 2014·Current Opinion in Critical Care·Claire MastersonBrian P Kavanagh
Mar 14, 2017·Canadian Respiratory Journal : Journal of the Canadian Thoracic Society·Scott D CollumHarry Karmouty-Quintana

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