trypsinogen and Fat-Necrosis

Unconscious rats given intravenous ceruletide (diethylamine salt of the decapeptide caerulein) in large pharmacologic doses consistently developed moderate acute pancreatitis by 3 h and florid pancreatitis by 6 h. Biochemical serum markers of acute pancreatitis tended to parallel the severity of the pancreatic damage. In 50% of the rats, mesenteric fat necrosis was present, free peritoneal fluid containing massive elevations of trypsinogen and amylase were noted in most animals. Intravenous secretion at a low dose given simultaneously with ceruletide exerted a variable protective effect on the pathological process. A high dose of secretin produced a striking macroscopic, microscopic, and biochemical protective effect on ceruletide-induced pancreatitis. High resolution light microscopy and electron microscopy showed a marked cellular disorganization in the acini of animals treated with ceruletide alone. By contrast, there was a striking apical redirection of zymogen granules in acini of the animals treated with secretin. The results of this study suggest that high dose intravenous secretin may exert a beneficial effect on acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ceruletide; Edema; Fat Necrosis; Lipase; Male; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Secretin; Trypsinogen

Three aspects of the pathophysiology of acute pancreatitis are discussed: 1. the initiating mechanisms, 2. the mechanisms of the fat necrosis, 3. the processes leading to shock phenomena. It is pointed out that the intraglandular activation of the precursors for both lipolytic and proteolytic enzymes seems to be essential for the initiating mechanisms of the disease. The role of the hormone dependent lipolytic enzyme of the fat tissue is discussed in relation to the occurrence of extrapancreatic fat necrosis. The role of the vaso-active compounds, such as plasma kinins and histamine for the occurrence of shock during acute hemorrhagic pancreatitis is pointed out.

Topics: Acute Disease; Chymotrypsin; Enzyme Activation; Enzyme Precursors; Fat Necrosis; Histamine Release; Humans; Kallikreins; Kinins; Pancreatic Elastase; Pancreatitis; Peptide Hydrolases; Phospholipases; Shock, Hemorrhagic; Triglycerides; Trypsin; Trypsinogen