| ObjectiveAcute pancreatitis (AP) is a disease of variable severity. Approximately 80% of patients have a relatively mild attack that resolves with little of no complications, the mortality rate is low. However, the 20% of patients in whom pancreatic necrosis develops may incur systemic complications and a mortality rate as high as 40%. Recent investigations have established that one of the earliest pathophysiologic events in pancreatitis is the colocalization of acinar cell or-ganelles containing digestive and lysosomal enzymes, resulting in premature in-tracellular activation of proteases. The individual pancreatic cell injury becomes magnified and propagated by inducing (through incompletely defined mediators) impaired microcirculation leukocyte adhesion, and leukocyte infiltration. These become central events in the pathogenesis of pancreatic necrosis and its ex-trapancreatic complications. Organ dysfunction occurs in one in four patients with acute pancreatitis, and 60% who die from pulmonary damage.Intercellular adhesion molecule-1(ICAM-1) and P - selectin are expressed on endothelial cells and are responsive to numerous inflammatory mediators. Both of them mediate leukocyte adhesion and migration through the endo-thelium into tissues. LFA - 1 and Mac - 1 are the counter receptors of ICAM -1 , both of them are expressed on leukocyte and are concerned with mediating both leukocyte adhesion and migration through the endothelium into tissues, too.Corticosteroids have well - known immunosuppressive effects including inhibition of the release of various cytokines. The role corticosteroid in the treatment of acute pancreatitis has been a matter of dispute. Earlier reports claimed beneficial effects both in human and experimental AP. By contrast, experimen-tal studies in rabbits and rats, and a number of case reports, have demonstrated an association of pancreatitis with steroid administration, although the basis for steroid - induced pancreatitis still remains unproven.It is our hypothesis that corticosteroids inhibit not only cytokines but also adhesion molecules and thereby improve the physiological derangement observed during AP. Therefor, the aim of the present study was to investigate the patho-physiological role of adhesion molecules, namely P - selectin, ICAM -1 and its counter receptors ( LFA-1 and Mac-1) , on mediating the systemic manifestations associated with severe necrotizing pancreatitis through neutralization of their effects by a well - known immunosuppressive drug like hydrocortisone.MethodAnimals, Anesthesia and Surgical ProceduresSprague - Dawley rats (250 to 300g) were fasted 12 hours before the experiment but were allowed free access to water. Fluothane , oxygen and nitrons oxide were used in surgical anesthesia ( 2 L/min). All rats underwent a 2 - cm -long midline laparotomy, and the pancreatic duct was ligated followed by injection of 5% chenodeoxycholic bile acid (1 ml/kg, Wako Pure Chemical Industries, Ltd. , Osaka, Japan) into the pancreas at multiple points.Experimental designA total of 75 rats was allocated to Hydrocortisone group, AP group and control group ( respectively 25 rats). The rats of AP group were pretreated with a subcutaneous bolus injection of 200 ul of 0.9% saline 30 min before induction of AP followed by injection of 200 ul of 0.9% saline intravenously for about 5 min. The rats of Hydrocortisone group were pretreated with hydrocortisone by a subcutaneous bolus injection ( 5mg/kg) followed by injection of hydrocortisone ( 5mg/ kg diluted in 200 ul 0.9% saline) intravenously for about 5 min before induction of AP, as mentioned previously. The rats of control group only received the laparotomy. Blood samples(2ml) were drawn by v. cava inferior, pancreatic and lung tissues were removed and processed as indicated below before the rats were killed at lh,3h,6h,12h and 24h after induction of pancreatitis(n =5 per group). Ascitic Fluid was quantified by weighing towels after absorption of the ascitic fluid from the abdominal cavity...
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