REPERFUSION INJURY AND EXHALED HYDROGEN-PEROXIDE

Reactive oxygen species have been implicated in the pathophysiology of lung injury associated with the sequence of ischemia-reperfusion. To study this, we measured the exhaled breath hydrogen peroxide concentra tion [H2O2] in human and canine models of reperfusion lung injury. Our models were patients subjected to cardiopulmonary bypass (CPB) (Group 1), patients undergoing pulmonary thromboendarterectomy (Group 2), ca nine single lung transplant (Group 3), and patients subjected to perip heral ischemia resulting from aortic cross-damping or tourniquet appli cation (Group 4). In addition, we studied two groups with severe lung injury as positive controls. These consisted of hydrochloric acid (HCI )-induced canine lung injury (Group 5) and patients with adult respira tory distress syndrome (Group 6). The exhaled H2O2 was collected by us ing a -2-degrees-C glass coil and assayed by a spectrophotometric meth od. hi Group 1 samples were collected before and immediately after CPB . Group 2 samples were obtained before CPB, immediately after CPB, 3 h later, and daily until extubation. Samples in Group 3 were collected before lung transplant, and hourly for 3 h beginning immediately after ward. Group 4 samples were collected at the onset of reperfusion. Samp les from Group 5 were collected before HCI and after HCI injury, at 0. 5-1.5 and 2-3 h. Group 6 samples were collected when criteria for adul t respiratory distress syndrome were met. Groups 1, 3, and 4 exhibited no significant increases in exhaled [H2O2] compared to control values . Group 2 had significantly increased [H2O2] (5.59 +/- 3.07 X 10(-7) m ol/L, P = 0.028) on postoperative Day 2, but there was no correlation of [H2O2] with physiologic indicators of lung injury. Group 5 had a dr amatic increase in the [H2O2] in the first post-HCI sample period (14. 92 X 10(-7) mol/L +/- 9.74 X 10(-7) mol/L, P = 0.046), which correlate d inversely with the respiratory index. Group 6 had significant increa ses in [H2O2] (5.45 +/- 2.02 X 10(-7) mol/L). In conclusion, exhaled H 2O2 was not increased immediately after reperfusion in any of the isch emia-reperfusion models but was significantly increased by postoperati ve Day 2 in the pulmonary thromboendarterectomy patients and in the co ntrol groups with severe lung injury. These findings suggest that H2O2 may be a mediator of, or marker for, diverse types of lung injury. Ho wever, the temporal sequence of pathophysiologic events and the exact significance of increased exhaled H2O2 is unclear at this time.