A clinically applicable porcine model of septic and @entity63 /reperfusion-induced shock and XXXX .

@entity1 @entity1707 @entity32 @entity295 @entity63 @entity326 @entity26 @entity8479 @entity1230 @entity130 @entity647
BACKGROUND: Although many @entity295 treatments have shown efficacy in acute animal models, at present only activated protein C is effective in @entity1 . The likely reason for this discrepancy is that most of the animal models used for preclinical testing do not accurately replicate the complex pathogenesis of @entity1 @entity295 . Our objective in this study was to develop a clinically applicable model of severe @entity295 and gut @entity63 /reperfusion (I/R) that would cause @entity1230 over a period of 48 h. MATERIALS AND METHODS: Anesthetized, instrumented, and ventilated @entity1707 were subjected to a "two-hit" injury by placement of a fecal clot through a laparotomy and by clamping the superior mesenteric artery (SMA) for 30 min. The animals were monitored for 48 h. Wide spectrum antibiotics and intravenous fluids were given to maintain hemodynamic status. FiO(2) was increased in response to @entity26 desaturation. Twelve hours following injury, a drain was placed in the laparotomy wound. Extensive hemodynamic, lung, kidney, liver, and renal function measurements and serial measurements of arterial and mixed venous blood gases were made. Bladder pressure was measured as a surrogate for intra-peritoneal pressure to identify the development of the @entity8479 ( @entity8479 ). Plasma and peritoneal ascites cytokine concentration were measured at regular intervals. Tissues were harvested and fixed at necropsy for detailed morphometric analysis. RESULTS: Polymicrobial @entity295 developed in all animals. There was a progressive deterioration of organ function over the 48 h. The lung, kidney, liver, and intestine all demonstrated clinical and histopathologic injury. @entity647 ( @entity647 ) and @entity8479 developed by consensus definitions. Increases in multiple cytokines in serum and peritoneal fluid paralleled the dysfunction found in major organs. CONCLUSION: This animal model of Sepsis+I/R replicates the systemic @entity32 and dysfunction of the major organ systems that is typically seen in @entity1 @entity295 and @entity130 @entity1 . The model should be useful in deciphering the complex pathophysiology of @entity326 as it transitions to end-organ injury thus allowing sophisticated preclinical studies on potential treatments.
