Experimental study on the pathogenesis of acute acalculous cholecystitis, with special reference to the roles of microcirculatory disturbances, free radicals and membrane-bound phospholipase A₂

Summary

To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A₂ (PIA₂) activity, content of lipid peroxide, and Superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PIA₂ activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PIA₂ activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PIA₂.