Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing

The purpose of the present study was to determine whether it is possible to alter the development of fatigue and ablate free radical-mediated lipid pe roxidation of the diaphragm during loaded breathing by administering oxypur inol, a xanthine oxidase inhibitor. We studied 1) room-air-breathing decere brate, unanesthetized rats given either saline or oxypurinol (50 mg/kg) and loaded with a large inspiratory resistance until airway pressure had falle n by 50% and 2) unloaded saline- and oxypurinol-treated room-air-breathing control animals. Additional sets of studies were performed with animals bre athing 100% oxygen. Animals were killed at the conclusion of loading, and d iaphragmatic samples were obtained for determination of thiobarbituric acid -reactive substances and assessment of in vitro force generation. We found that loading of saline-treated animals resulted in significant diaphragmati c fatigue and thiobarbituric acid-reactive substances formation (P < 0.01). Oxypurinol administration, however, failed to increase load trial time, re duce fatigue development, or prevent lipid peroxidation in either room-air- breathing or oxygen-breathing animals. These data suggest that xanthine oxi dase-dependent pathways do not generate physiologically significant levels of free radicals during the type of inspiratory resistive loading examined in this study.