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Objective: The cytoprotective enzyme heme oxygenase 1 (HO-1) is highly up-regulated in acute pancreatitis (AP). In this study, we tested its metabolites as potential therapeutic agents for AP in rats., Methods: Acute necrotizing pancreatitis was induced by retrograde intraductal injection of sodium taurocholate in rats. Biliverdin hydrochloride (BV HCl) (50 μmol/kg subcutaneously), the carbon monoxide, donor methylene chloride (MC) (500 mg/kg orally), or iron-chelating desferrioxamine (DFO) (125 mg/kg subcutaneously) were administered in a therapeutic manner starting with the first dose 4 hours after taurocholate injection to mimic the effects of HO-1 metabolites., Results: Administration of BV HCl, MC, or DFO showed significant reduction of inflammatory activity in comparison to controls leading to lower myeloperoxidase activity in the pancreas, less edema, lower ascites volumes, and preservation of tissue integrity (P < 0.05). Administration of either BV HCl or MC markedly increased 5-day survival rate (70% and 75% vs 40%; P < 0.05), whereas DFO had no significant effect on survival (60%). When given in therapeutic manner, all 3 substances led to diminished nuclear factor κB activity in the pancreas (P < 0.05)., Conclusions: Therapeutic use of BV HCl and MC led to marked reduction of mortality in experimental pancreatitis. Thus, HO-1 metabolites may present a novel therapeutic approach in AP treatment.

Objective: To assess the balance between trypsin and protease inhibitors simultaneously in the systemic circulation and in the thoracic lymph and peritoneal exudate., Methods: Twenty patients with early severe acute pancreatitis were studied. Enzymatically active and immunoreactive trypsin in conjunction with its major inhibitors were measured in the 3 compartments at the onset of end-organ failure(s). The molecular forms of trypsin were determined in the lymph and ascites by gel filtration chromatography to separate trypsinogen and free-and inhibitor-bound trypsin., Results: Both enzymatically active trypsin and immunoreactive trypsin levels were highest in ascites and lymph compared with the systemic circulation. Intracompartmental alpha1- protease inhibitor gradient moved in the opposite direction, whereas alpha2 macroglobulin concentration was highest in ascites and lowest in the lymph. Although most of the enzymatically and immunoreactive material in ascites and lymph consisted of trypsin complexed with alpha2 macroglobulin and trypsinogen, respectively, free active trypsin was detected in more than 80% of the samples., Conclusions: In patients with early severe acute pancreatitis, there is a significant trypsinogen activation resulting in protease-antiprotease imbalance and thereby free enzymatically active trypsin in the 2 body fluid compartments in close vicinity to the inflammatory process. This may be involved in the pathophysiology of local and distant tissue damage.

Pancreatic ascites is a rare complication of chronic pancreatitis, whose treatment continues to represent a difficult clinical problem. In this report we describe a case of a patient with chronic pancreatitis and pancreatic ascites who was successfully treated with somatostatin given by continuous intravenous infusion of 1.5 micrograms/kg/h for 2 weeks.