Hypercapnic acidosis reduces oxidative reactions in endotoxin-induced lung injury

Abstract

Background: Hypercapnic acidosis frequently occurs when patients with acute lung injury are initially ventilated with low tidal volume " protective" strategies. Hypercapnic acidosis per se, in the absence of any change in tidal volume or airway pressure, is protective when instituted before the onset of injury. However, the mechanisms by which hypercapnic acidosis confers this protection are incompletely understood, in particular, the effects on pulmonary oxidative reactions, which are potent mediators of tissue damage, have not been previously examined in vivo. Methods: After anesthesia, tracheostomy, and the intratracheal instillation of endotoxin to establish lung injury, rats were mechanically ventilated for 6 h in normocapnia (21% O 2, 0% CO2). Rats were then randomized to either normocapnic (21% O2, 0% CO2) or hypercapnic (21% O 2, 5% CO2) ventilation and a nonspecific nitric oxide synthase inhibitor (N-monomethyl-l-arginine) or vehicle. Dihydrorhodamine was administered intravenously, and the lungs were removed for determination of the oxidative formation of rhodamine by spectrofluorimetry after 20 min. Thus, rats were randomly assigned to either: normocapnia-endotoxin (n = 12), normocapnia-endotoxin-N-monomethyl-l-arginine (n = 9), hypercapnia-endotoxin (n = 11), or hypercapnia-endotoxin-N-monomethyl-l-arginine (n = 10). Results: Hypercapnic acidosis significantly reduced the pulmonary oxidative reactions in the inflamed lung compared with normocapnia. Nitric oxide synthase blockade did not alter endotoxin-induced oxidative reactions. Conclusions: Hypercapnic acidosis reduced oxidative reactions in the acutely injured lung in vivo, within minutes of onset and was not reliant on nitric oxide-dependent peroxynitrite production. This rapid onset antioxidant action is a previously undescribed mechanism by which hypercapnic acidosis could act, even when acute lung injury is well established. Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.