Oxygen uptake-oxygen delivery alterations in the isolated liver after hydrogen peroxide challenge

Acute, diffuse lung injury is frequently complicated by systemic organ injury and alterations in the relationship between oxygen uptake (VO2) and oxygen delivery (QO2). In this regard, systemic organ neutrophil accumulation and morphologic alterations consistent with systemic organ injury often occur in nonpulmonary organs in these settings. However, whether VO2-QO2 matching is also altered in these injured systemic organs remains unproven. Thus, the present study was designed to test the hypothesis that hydrogen peroxide (H2O2), a product of neutrophil oxidative metabolism, will cause systemic organ structural abnormalities and alter VO2-QO2 matching. To test this hypothesis, VO2-QO2 relationships, morphologic changes, and organ water content were evaluated in both uninjured, isolated perfused rabbit livers and in isolated perfused rabbit livers after injury with 5 mmol/L H2O2. Following H2O2 injury, peak VO2 fell from 1.36 +/- 0.35 mL/min/100 g to 0.79 +/- 0.16 mL/min/100 g (P < .05) and peak O2 extraction fell from 0.83 +/- 0.09 to 0.66 +/- 0.04 (P < .05). In addition, VO2 was lower for any given level of QO2 in the H2O2-injured livers compared with the control livers (P < .01). Finally, liver extravascular water content was increased in H2O2-injured livers compared with the control livers (0.79 +/- 0.02 v 0.71 +/- 0.05; P < .05). These observations indicate that H2O2, a product of neutrophil oxidative metabolism, is capable of producing both morphologic changes as well as gas exchange alterations in the isolated, perfused liver.