Very little is known about the pathogenesis of acute pancreatitis. Therefore, treatment consists primarily of supportive and symptomatic care. Many disorders and clinical situations are known to initiate episodes of acute pancreatitis. These include alcohol intake, gall stones, and ischemia. Exact pathogenetic mechanisms by which these stimuli cause pancreatitis, however, are unknown. Utilizing the ex-vivo, isolated, perfused canine pancreas model, experimental pancreatitis can be initiated by a variety of stimuli simulatilng clinical situations. Alcoholic hyperlipemic pancreatitis can be simulated in this preparation by infusing oleic acid (FFA) into the arterial line. Gall stone pancreatitis can be simulated by partially obstructing the pancreatic duct and maximally stimulating the gland. Ischemic pancreatitis can be induced in this preparation by a period of total ischemia before the perfusion is started. In all three of these instances the first physiologic change in the pancreas is an increase in capillary permeability. The pancreatitis can be modified or abated by the addition of an osmotically active agent, such as albumin. Furthermore, this capillary injury appears to be mediated at least in part, by oxygen-derived free radicals. By studying the pathogenetic pathways of experimental pancreatitis in this isolated organ model, it is hoped that effective treatment can be derived. A clinical trial evaluating the use of nasogastric suction in acute pancreatitis will be continued, and a clinical study evaluating albumin administration in severe acute pancreatitis will be initiated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032435-05
Application #
3230825
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Nordback, I H; Chacko, V P; Cameron, J L (1994) Induction of anaerobic glucose metabolism during the development of acute pancreatitis. Ann Surg 219:248-57
Nordback, I H; Cameron, J L (1993) The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preparation. Surgery 113:90-7
Nordback, I H; Olson, J L; Chaisson, R E et al. (1992) Acute effects of a nucleoside analog dideoxyinosine (DDI) on the pancreas. J Surg Res 53:610-4
Nordback, I H; Clemens, J A; Cameron, J L (1991) The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. Surgery 109:301-6
Nordback, I H; Clemens, J A; Chacko, V P et al. (1991) Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. Ann Surg 213:341-9
Nordback, I H; MacGowan, S; Potter, J J et al. (1991) The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis. Ann Surg 214:671-8