HYPERCAPNIC ACIDOSIS MAY ATTENUATE ACUTE LUNG INJURY BY INHIBITION OFENDOGENOUS XANTHINE-OXIDASE

Relative hypoventilation, involving passively-or ''permissively''-gene rated hypercapnic acidosis (HCA), may improve outcome by reducing vent ilator-induced lung injury. However, the effects of HCA per se on pulm onary microvascular permeability (K-f,K-c) in noninjured or injured lu ngs are unknown. We investigated the effects of HCA in the isolated bu ffer-perfused rabbit lung, under conditions of: (I) no injury; (2) inj ury induced by warm ischemia-reperfusion; and (3) injury induced by ad dition of purine and xanthine oxidase. HCA (fraction of inspired carbo n dioxide [FICO2] 12%, 25% versus 5%) had no adverse microvascular eff ects in uninjured lungs, and prevented (FICO2 25% versus 5%) the incre ase in K-f,K-c following warm ischemia-reperfusion. HCA (FICO2 25% ver sus 5%) reduced the elevation in K-f,K-c, capillary (Pcap), and pulmon ary artery (Ppa) pressures in lung injury induced by exogenous purine/ xanthine oxidase; inhibition of endogenous NO synthase in the presence of 25% FICO2 had no effect on K-f,K-c, but attenuated the reduction o f Pcap and Ppa. HCA inhibited the in vitro generation of uric acid fro m addition of xanthine oxidase to purine. We conclude that in the curr ent models, HCA is not harmful in uninjured lungs, and attenuates inju ry in free-radical-mediated lung injury, possibly via inhibition of en dogenous xanthine oxidase.