ESTABLISHMENT AND EVALUATION OF ANIMAL MODELS TO ELUCIDATE THE PATHOPHYSIOLOGY OF MULTIPLE ORGAN DYSFUNCTION SYNDROME

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[1] We have previously reported that intestinal ischemia-reperfusion (I/R) produced lung injury via a mechanism which involves phospholipase A2 (PLA2) activation. In this study we hypothesized that group IIA PLA2 is the responsible isozyme. Intestinal I/R provoked intestinal leak, liver injury, and lung leak, while tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera, and only abolished lung leak. Intestinal ischemia-reperfusion appears to produce lung injury via a mechanism which involves group IIA PLA2 activation. Intestinal I/R is likely to promote intestinal and hepatic injury independent of group IIA PLA2.[2] While various animal models have been used to elucidate what causes multiple organ failure, definite methods to estimate systemic organ damage, especial … More ly endothelial injury, have not well been established in mice. We attempted to establish simple methods that enable us to detect intestinal, pulmonary, and hepatic injury in a murine model of intestinal I/R. Adult female BALB/c mice underwent 45 minutes of superior mesenteric artery occlusion. Two and 6 hours after reperfusion, microvascular permeability and edema formation in the intestine, lung, and liver, were quantitated by Evans blue method (EB) and wet/dry ratio (W/D), respectively. Liver function was also measured by plasma alanine aminotransferase (ALT) and total bilirubin (T-Bil) concentrations. In BALB/c mice, intestinal injury was detected by EB and W/D, and increased pulmonary permeability was measured by EB. Liver injury was quantitated by EB, W/D, and T-Bil. In C57BL/6 mice, intestinal injury was estimated by EB and W/D, lung leak by EB, and liver injury by W/D, ALT, and T-Bil. While slight difference was observed between those two strains of mice, intestinal, pulmonary and hepatic injury could be successfully estimated by the combination of EB, W/D, ALT and T-Bil in a murine model of intestinal I/R. These methods may become useful in mice not only to delineate the mechanisms linking intestinal I/R and remote organ injury but also in other fields of shock research. Less