Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

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In acute pancreatitis, reductions in blood flow and alterations of microvascular integrity resulting in impaired tissue oxygenation play an important part in the progression and possibly the initiation of the disease. Independently of the initial noxa, the intra-pancreatic activation of trypsinogen to trypsin is the crucial trigger of acute pancreatitis. The central events for the further course are the release of local mediators (cytokines, vasoactive substances, free oxygen radicals) and subsequently the development of microcirculatory disturbances and the activation of leukocytes and their infiltration into the tissue. At present, the deterioration of microcirculation is seen as the most important pacemaker in the progression to a necrotizing pancreatitis. In addition to its potentiatory role, severe pancreatic ischemia can play a pathogenetic role in the initiation of acute pancreatitis. The acute edematous pancreatitis is characterized by an increased and homogeneous microperfusion. The experimental necrotizing pancreatitis shows a progredient decrease of capillary perfusion despite stable macrohemodynamics. There is increasing evidence that ischemia alone may be the primary cause of pancreatitis or may be the exacerbating promotor for the progression from edematous to necrotizing pancreatitis. In clinical studies there was evidence, that ischemia during cardiopulmonary bypass triggered acute pancreatitis and acute pancreatitis was found in up to 25% of autopsies of patients dying after shock. In animal models severe pancreatitis could be induced by obstruction of terminal pancreatic arterioles. The study by Mithofer et al. [1] demonstrates, that temporary hemorrhagic hypotension in rats per se initiates acute pancreatitis. The hypothesis, that the manifestation of microvascular injury in acute pancreatitis involves ischemia/reperfusion(I/R)-associated events, is supported by the study of Menger et al. [2], who analyzed the pancreatic microcirculation of rats during postischemic reperfusion by use of intravital fluorescence microscopy (Fig. 1, 2). In this investigation, post-ischemic reperfusion was characterized by a significant reduction of functional capillary density (noreflow) and by a marked increase of the permanently adherent leukocytes in postcapillary venules (reflow paradox) (Fig. 3). In addition, the functional and histomorphological alterations in this study were similar to the alteration seen in edematous pancreatitis. Postischemic activation of leukocytes has been reported to determine the outcome of I/R injury. Kusterer et al. [3] have demonstrated that sodium taurocholate-induced pancreatitis