Role of ischemia in acute pancreatitis

Abstract

Ischemia has been considered to play a role in the development of acute pancreatitis. The aim of this study was to investigate the effect of ischemia, caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by the intravenous infusion of a supramaximally stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock was induced by the removal of blood until the mean arterial blood pressure reached 35 mm Hg. This level was maintained for 30 min, after which time all the blood was reinfused. Hemorrhagic shock alone induced no morphological change in the pancreas. However, after the induction of hemorrhagic shock in animals treated with cerulein, hemorrhage and parenchymal necrosis were frequently observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas none of the rats in the cerulein or shock group died during this experiment. Cathepsin B activity in the pancreas of the cerulein plus shock group was significantly higher than in the other groups at 48 hr. These results suggest that ischemia may be a contributing factor in the pathogenesis of acute pancreatitis.

Blocking abdominal lymphatic flow attenuates acute hemorrhagic necrotizing pancreatitis -associated lung injury in rats

“…After de-paraffinization, sections were stained with hematoxylin and eosin stain and examined by two investigators in a blinded manner. The specimens of lung and pancrease were scored according to the criteria described previously [8,9]. The intestinal mucosal injury score was graded on a six-tiered scale defined by Chiu [10].…”

Ischemia/Reperfusion-Induced Pancreatitis

“…An ongoing argument is whether ischemia/reperfusion injury itself causes AP or rather serves as a cofactor that converts the initial insult to the pancreas into a necrotizing pancreatitis [10, 14, 19, 20]. This controversy is further complicated by suggestions that ischemia/reperfusion-induced pancreatic injury may represent a different phenomenon from AP of other etiologies [131].…”

“…Ischemic injury to the pancreas has been demonstrated both experimentally and clinically [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30]. After intra-arterial injection of occluding microspheres into the pancreatic circulation, the severity of the resultant AP varies with the size of the particles [25, 26].…”

“…Ischemia and reperfusion of the ex vivo pancreas induces parenchymal edema associated with release of amylase into the perfusion fluid [30]. Ischemia superimposed on otherwise reversible edematous AP in in vivo rat models of Spormann et al [19]and Kyogoku et al [20]led to progression to irreversible necrotizing pancreatitis; total ischemia for 2 h, followed by reperfusion led to histologically confirmed hemorrhagic necrotizing pancreatitis in all animals [19, 20]. The morphological changes were similar to those observed in man in severe, necrotizing pancreatitis [32], pancreatitis after pancreas transplantation [33], and in other models of severe experimental pancreatitis in several different species (cat, dog, rat, pig, opossum) [34, 35, 36].…”

Importance of Microcirculatory Disturbances in the Pathogenesis of Pancreatitis

“…The study by Mithöfer et al demonstrates, that temporary hemorrhagic hypotension in rats per se initiates acute pancreatitis [55]. Two other investigations in rats show that aterial hypotension aggravates microvascular perfusion [31] and that hemorrhagic shock converts edematous to hemorrhagic pancreatitis [42]. However, single exposure to alcohol or hyperlipidemia induces microcirculatory disturbances in animal studies, but no pancreatitis [32].…”