TIME-COURSE OF BACTERIAL-INFECTION OF THE PANCREAS AND ITS RELATION TO DISEASE SEVERITY IN A RODENT MODEL OF ACUTE NECROTIZING PANCREATITIS

Background Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and diffic ult to study in humans. Objective The time course of bacterial infecti on oi the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis. Methods Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infus ion of cerulein (5 mu g/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycode oxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min fo r severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals we re killed for quantitative bacterial examination and histologic scorin g of necrosis. In addition, groups of animals with severe AP were inve stigated at 12, 24, 48, 96, and 144 hours. Results No significant panc reatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1. 1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals wit h severe AP. Control animals did not develop significant bacterial inf ection of the pancreas (greater than or equal to 10(3) CFU/g). At 96 h ours, the prevalence of infection was 37.5% in animals with mild AP an d 50% in animals with moderate AP. In animals with severe AP, infectio n of the pancreas increased from 33% in the first 24 hours to 75% betw een 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g ) at 96 hours. Conclusion Bacterial infection of the pancreas in roden t AP increases during the first several days, and its likelihood corre lates with the severity of the disease. This model, which closely mimi cs the features of human acute pancreatitis, provides a unique opportu nity to study the pathogenesis of infected necrosis and test therapeut ic strategies.