Multiple organ dysfunction after remote circulatory arrest: Common pathwayof radical oxygen species?

Objectives: Cardiovascular, respiratory, and vascular dysfunction can follo w trauma-induced no-flow-reflow states: hemorrhage, blunt trauma, or neurog enic shock, Liver ischemia-reperfusion (IR) induces remote lung damage by m eans of xanthine oxidase (XO) pro-oxidant activity, This damage was not pro ven in the heart, neither was the independent role of radical oxygen specie s (ROS) established in such cases. We investigated whether multiple organ d ysfunction after a trauma-like IR is XO and ROS related and whether clinica lly used ROS scavengers could be beneficial. Methods: A controlled, randomized trial in which isolated rat livers, heart s, lungs, and aortic rings were perfused with Krebs-Henseleit solutions. Af ter stabilization, livers were either perfused or made ischemic (2 hours). Then, pairs of liver plus heart, lung, or ring were repel fused in series ( 15 minutes), and then the second organ circulated alone for 45 minutes, Rem ote organ protection against the pro-oxidant hepatic-induced toxicity was e valuated by using allopurinol (1 mmol/L, heart), mannitol (0.25 g/kg, lung) , or methylene blue (40 mg/kg, ring). Results: IR liver effluents typically contained high lactate dehydrogenase, XO, and uric acid concentrations compared with control organs. IR was asso ciated with doubled lung peak inspiratory pressure and reduced static compl iance, Myocardial velocity of contraction and relaxation decreased by one t hird of baseline, and rings contracted abnormally and responded inadequatel y to phenylephrine. Wet-weight to dry-weight ratios in the remote organs in creased as well, Most remote reperfusion injuries were attenuated by the dr ugs, Conclusion: Liver no-flow-reflow directly induces myocardial, pulmonary, an d vascular dysfunction, These are likely mediated by XO and ROS, The tested drugs protected against these pro-oxidants, even in the presence of circul ating XO.