Abstract P198: Redox Monitoring Reveals Increased Susceptibility of Whole Blood to Oxidative Stress During Hemorrhagic Shock

Abstract

Introduction: The oxidation/reduction (redox) chemistry of blood during resuscitation is not well defined. Improved understanding of whole blood redox behavior would assist in developing better resuscitation monitoring and possibly reducing free radical injury both of which are PULSE initiative priorities. We use direct electrochemical measurement of equilibrium redox potential to assess the hypothesis that the overall response of blood to strong oxidant/reductant challenge is altered during shock. Methods: Five swine underwent hemorrhage to an oxygen debt (OD) of 80 cc/kg. Arterial blood was tested at baseline (BL) and after hemorrhage when OD equaled 40 and 80 cc/kg. Native redox potential was measured as the equilibrium voltage potential recorded between a freshly polished 2mm Au and standard Ag/AgCl electrode submerged in whole blood (n=34). The oxidative and reductive stress responses at each level of OD were defined as the change from native voltage potential induced by the addition of a strong oxidant (KMnO4) (n=18) or reductant (Dithiotreitol) (n=18). Mean native redox potentials and mean redox stress responses were compared for differences at increasing levels of OD using repeated measures ANCOVA. Results: Lactate increased significantly with OD (mean diff BL vs. OD=80, +4.7 mmol/L [1.3, 8.1]). No effect of OD was found on native redox potential (p value =0.233). A significant effect of OD was found on redox stress response (p value =0.0276). The redox response to oxidative stress increased from BL with increasing oxygen debt, and became significantly greater at OD=80 cc/kg (mean diff =+31.9 Rmv [3.9, 59.9]). Conclusions: Whole-blood redox potential did not change significantly even with severe shock, suggesting active redox buffering. However, our results suggest that the oxidative buffering capacity of blood may become impaired during severe shock as demonstrated by the significantly more positive redox potentials elicited by oxidative stress when OD was elevated. Impaired redox buffering during shock may exacerbate free radical injury induced by the oxidative stress of resuscitation. Monitoring the response of blood to oxidative stress may be a useful way to determine susceptibility to oxidative damage during resuscitation.