Multiple organ dysfunction after remote circulatory arrest: common pathway of radical oxygen species?
OBJECTIVE
Cardiovascular, respiratory, and vascular dysfunction can follow trauma-induced no-flow-reflow states: hemorrhage, blunt trauma, or neurogenic shock. Liver ischemia-reperfusion (IR) induces remote lung damage by means of xanthine oxidase (XO) pro-oxidant activity. This damage was not proven in the heart, neither was the independent role of radical oxygen species (ROS) established in such cases. We investigated whether multiple organ dysfunction after a trauma-like IR is XO and ROS related and whether clinically used ROS scavengers could be beneficial.


METHODS
A controlled, randomized trial in which isolated rat livers, hearts, lungs, and aortic rings were perfused with Krebs-Henseleit solutions. After stabilization, livers were either perfused or made ischemic (2 hours). Then, pairs of liver plus heart, lung, or ring were reperfused in series (15 minutes), and then the second organ circulated alone for 45 minutes. Remote organ protection against the pro-oxidant hepatic-induced toxicity was evaluated 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 associated with doubled lung peak inspiratory pressure and reduced static compliance. Myocardial velocity of contraction and relaxation decreased by one third of baseline, and rings contracted abnormally and responded inadequately to phenylephrine. Wet-weight to dry-weight ratios in the remote organs increased as well. Most remote reperfusion injuries were attenuated by the drugs.


CONCLUSIONS
Liver no-flow-reflow directly induces myocardial, pulmonary, and vascular dysfunction. These are likely mediated by XO and ROS. The tested drugs protected against these pro-oxidants, even in the presence of circulating XO.
Weinbroum
A A
AA
Department of Anesthesiology, Tel-Aviv Sourasky Medical Center, Israel. daw111@ibm.net
Hochhauser
E
E
Rudick
V
V
Kluger
Y
Y
Karchevsky
E
E
Graf
E
E
Vidne
B A
BA
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006323:Heart Arrest / Q000150:complications*; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D008751:Methylene Blue / Q000627:therapeutic use; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D009104:Multiple Trauma / Q000150:complications*; D009206:Myocardium / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008353:Mannitol; D000493:Allopurinol; D014969:Xanthine Oxidase; D008751:Methylene Blue