Pancreatic ischaemia in experimental acute pancreatitis: Mechanism, significance and therapy

Abstract

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.

Effects of 17ß-Estradiol on the Acute Necrotizing Pancreatitis after Onset in Rats

“…Auto digestion ofthe pancreas by activated digestive enzymes, ischemia ofthepancreas, apoptosis and ischemia-related reactive oxygen species (ROS)-associated lipid peroxidation cause pancreatic damage during acute pancreatitis (2-4, 24, 25). Microcirculation disturbance is an important pathogenetic factor during acute pancreatitis (3)(4)(5). The microcirculation of the pancreas can be measured by diffuse reflectance spectroscopy, intravital microscopy, multiple indicator dilution technique, and orthogonal polarization imaging (3,4,29).…”

“…Microcirculation disturbance is an important pathogenetic factor during acute pancreatitis (3)(4)(5). The microcirculation of the pancreas can be measured by diffuse reflectance spectroscopy, intravital microscopy, multiple indicator dilution technique, and orthogonal polarization imaging (3,4,29). We measured pancreatic microcirculation by orthogonal polarization imaging in this study.…”

Is the pancreas affected in patients with septic shock? — a prospective study

“…[9,10] In addition, microvascular perfusion failure is a characteristic hallmark of pancreatitis. [10][11][12] Since Panum [13] presented the first report, other researchers have reported that the pancreas is highly sensitive to ischemia. [14][15][16][17][18] In humans, acute pancreatitis may develop after embolic closure of the vessels supplying the pancreas, [19] after hypoperfusion of the pancreas during cardiac surgery [20,21] and surgery for thoraco-abdominal aneurysms, [22] after splanchnic hypoperfusion, [23] or after pancreatic transplantation.…”

Sorafenib-Induced Pancreatitis

“…1. A cross-section from the abdominal computed tomography scan of the patient after developing pancreatitis endothelial permeability (Klar et al, 1990). MitogenActivated Protein Kinase (MAPK) is a downstream effector of Ras/Raf/MEK/ERK pathway and found to be activated in acute pancreatitis (Murr et al, 2003).…”