Arterial constriction, ischemia-reperfusion, and leukocyte adherence in acute pancreatitis

Abstract

We investigated microcirculatory changes in sodium taurocholate (ST)-induced pancreatitis. Groups of rats received as tracer either fluorescein isothiocyanate-dextran or acridine orange intravenously. The microcirculation of the exposed pancreas was observed by use of a video camera attached to an epi-illumination microscope. Vessel diameters and plaques of adherent leukocytes were measured with a digital image-analyzing system. In contrast to 0.4 ml of saline, intraductal infusion of ST (4%, 0.4 ml) induced a constriction of interlobular pancreatic arteries of 79 +/- 2% (P < 0.01) within 2 min. This constriction could not be antagonized by the leukotriene antagonist CGP-35949B. The radical scavengers superoxide dismutase (SOD) and N-(2-mercaptopropionyl)glycine (MPG) prevented the arterial constriction. Constriction of pancreatic arteries was accompanied by a decrease of erythrocyte velocity in the pancreatic capillaries. Flux in the head of the pancreas measured by laser-Doppler velocimetry decreased from 300 +/- 69 to 74 +/- 23 perfusion units (P < 0.01) after 446 +/- 159 s. Subsequently an increase of perfusion values was observed indicating reperfusion phenomena. ST induced leukocyte adherence to the walls of interlobular veins forming plaques constituting 39% of the observed venular cross section within 6 min. The leukotriene antagonist, SOD, or MPG prevented leukocyte adherence. Arterial constriction followed by ischemia-reperfusion and leukocyte adherence to venular endothelium during the reperfusion period represented the sequence of microcirculatory changes in ST-induced pancreatitis. The radical scavengers SOD and MPG prevented arterial constriction and leukocyte adherence to venular endothelium, indicating the involvement of free radicals in the pathogenesis of ST-induced pancreatitis in the rat.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

“…as reported by previous studies [3,7,16,25] . The decrease was -96% within 15 min and pancreatic microcirculatory blood flow remained low until the end of the experiment.…”

“…The pathophysiology of AP is incompletely understood but alteration in the pancreatic microcirculatory blood flow has been involved. Thus, a decrease in pancreatic blood flow occurs early in the course of AP and has been sug gested to play a role in the conversion of edematous to necrotizing AP [3][4][5][6][7] . The microcirculatory dysfunction includes arterial vasoconstriction with hypoperfusion, ischemia-re perfusion injur y, and obstruction of the venous outflow [8][9][10][11] .…”

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation

“…Various mechanisms have been suggested to explain the effects of IPC, such as activation of adenosine, adrenergic, bradykinin, and opioid receptors, activation of intracellular mediators such as protein kinase C , tyrosine kinases and the adenosine triphosphate (ATP)-sensitive potassium channels in the mitochondria1 membrane, expression of heat shock proteins, synthesis of antioxidant enzymes, and many others [30,31,321. However, there is still an ongoing discussion as to whether these effects represent causes, effects, or just epi-phenomena There is a high level of evidence that microcirculatory derangement caused by I/R injury plays a pivotal role in the pathogenesis of pancreatitis [33,34,35,36,371. Structural and functional damage in I/R injury results in leukocyte accumulation and adherence to venules, platelet aggregation, vasoconstriction and deterioration of capillary perfusion, which can be quantified by intravital fluorescence microscopy [38].…”

A Novel Diamino-Pyridine Derivative Prevents Excessive Leukocyte Infiltration in Aggravation of Acute Necrotizing Pancreatitis

“…This significant increase in control can be speculated as a consequence of surgical manipulations including laparotomy [23]. Acridine orange, used as fluorescent marker for leukocytes in a previous report in a pancreatitis model [24], had been proven to influence CD11b-mediated neutrophil adhesion to a bovine serum albumin matrix in vitro [25]. In our experiments, rhodamine 6G was applied as a dye for leukocytes, since it has no influence on the factors involved in leukocyte endothelial cell interaction.…”