Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is characterized by edema, acinar cell necrosis, hemorrhage, and severe inflammation of the pancreas. Patients with AP present with elevated blood and urine levels of pancreatic digestive enzymes, such as amylase and lipase. Severe AP may lead to systemic inflammatory response syndrome and multiorgan dysfunction syndrome, which account for the high mortality rate of AP. Although most (>80%) cases of AP are associated with gallstones and alcoholism, some are idiopathic. Although the pathogenesis of AP has not yet been elucidated, a common feature is the premature activation of trypsinogen within pancreatic tissues, which triggers autodigestion of the gland. Recent advances in basic research suggest that etiologic factors including cyclooxygenase-2, substance P, and angiotensin II may have novel roles in this disease. Basic research data obtained thus far have been based on animal models of AP ranging from mild edematous pancreatitis to severe necrotizing pancreatitis. In view of this, an adequate selection of experimental animal models is of paramount importance. Notwithstanding these animal models, it should be emphasized that none of these models mimic the clinical situation where varying degrees of severity usually occur. In this review, commonly used animal models of AP will be critically evaluated. A discussion of recent advances in our knowledge about AP risk factors is also included.

A Novel Model of Severe Gallstone Pancreatitis: Murine Pancreatic Duct Ligation Results in Systemic Inflammation and Substantial Mortality

“…Existing models associated with systemic inflammation, multiorgan dysfunction and mortality (e.g. CDE-diet-induced acute pancreatitis, retrograde duct injection-induced acute pancreatitis) differ in that they do not closely mimic human etiologies of the disease [6,7,8,9]. For instance, the CDE diet is not known to cause acute pancreatitis in humans, and acute lung injury can occur with a CDE diet independently of acute pancreatitis [7].…”

“…As acute lung injury is the major determinant of morbidity and mortality in human acute pancreatitis of any cause [5], our novel model of duct-ligation-induced acute pancreatitis in mice is of particular clinical relevance. Furthermore, the analogy of PD ligation to gallstone obstruction of the PD is of greater clinical relevance in comparison to several existing experimental models of acute pancreatitis such as induction by cerulein, choline-deficient ethionine-supplemented (CDE) diet or arginine [6,7,8,9]. Finally, in vivo gene modulation techniques and the increasing availability of transgenic mice are excellent examples of the applicability of this new experimental model to investigate the pathogenesis or treatment of pancreatic inflammation, systemic inflammation, acute lung injury and multiorgan dysfunction – that lead to death in acute pancreatitis.…”

“…CDE-diet-induced acute pancreatitis, retrograde duct injection-induced acute pancreatitis) differ in that they do not closely mimic human etiologies of the disease [6,7,8,9]. For instance, the CDE diet is not known to cause acute pancreatitis in humans, and acute lung injury can occur with a CDE diet independently of acute pancreatitis [7]. The retrograde duct injection model and its variations are noted for the mechanical trauma to the pancreatic ductal system that occurs which may not replicate the early stages of human gallstone pancreatitis [6,8].…”

Metabonomic investigations into the global biochemical sequelae of exposure to the pancreatic toxin 1‐cyano‐2‐hydroxy‐3‐butene in the rat

“…Urine samples were prepared for 1 ] propionate) and 3 mM sodium azide. All samples were centrifuged at 1800 g for 5 min to remove any solid material.…”

“…Several model compounds have been used experimentally to induce pancreatitis in animals to investigate the time-course and biochemical sequelae of pancreatic injury. [1] In the present study, we have chosen to investigate the toxic effects of 1-cyano-2-hydroxy-3-butene (CHB, crambene) ( Fig. 1), a stable breakdown product of natural glucosinolates present in many cruciferous plants, which is known to produce pancreatic acinar cell apoptosis at low to moderate doses.…”