Ischemia and reperfusion in pancreas.
Ischemic diseases of heart and brain are the primary causes of mortality in industrialized nations. The ischemic injury with the consecutive reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Recent evidence suggests that oxygen-derived free radicals and activated polymorphonuclear leukocytes produced in ischemic tissue are instrumental in the development of ischemic cell injury. In pancreas, ischemia/ reperfusion is proposed as a potentially damaging factor accounting in part for the pathogenesis of acute pancreatitis. Apart from ischemia/reperfusion injury, the kallikrein-kinin system mediates acute inflammation associated with enhanced capillary permeability and accumulation of polymorphonuclear leukocytes, cardinal features of ischemia/reperfusion injury also in acute pancreatitis. Therefore, it seems reasonable to use bradykinin-antagonists to influence postischemic reperfusion injury of the pancreas. In the following, we describe the pathophysiology of ischemia/reperfusion injury with special reference to the pancreatic microcirculation and morphological changes as observed in a model of complete and reversible ischemia. Furthermore, we will discuss the effects of two bradykinin-antagonists (HOE 140 and CP-0597) on functional integrity of the pancreas after ischemia/ reperfusion.
Hoffmann
T F
TF
Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany.
Leiderer
R
R
Harris
A G
AG
Messmer
K
K
D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D002196:Capillaries / Q000473:pathology; D004727:Endothelium / Q000166:cytology / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008833:Microcirculation; D008854:Microscopy, Electron; D010179:Pancreas / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D010195:Pancreatitis / Q000503:physiopathology*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*
C065679:icatibant; D001920:Bradykinin