Development of an experimental model of severe acute pancreatitis with organ failure.

Abstract

BACKGROUND: Severe acute pancreatitis (AP) is associated with organ failure. The current animal models of severe AP assess organ failure through surrogate markers such as histopathological evidence of necrosis or biochemical mediators of inflammation, which do not directly measure organ dysfunction seen in human AP. We developed a rat model of severe AP and measured clinically relevant end points of cardiovascular, respiratory and renal failure. METHODS: Adult male Wistar rats were divided into 3 groups. Group 1 included sham-operated rats, group 2 included rats with pancreatic duct ligation, and group 3 included rats with pancreatic duct ligation + intraperitoneal L-arginine administration. The common carotid artery was cannulated prior to intervention and at 48 h post-intervention to measure invasive blood pressure, heart rate, arterial blood gases, pH, and renal and liver function tests. The pancreas, lung, and kidney tissues were subjected to histopathology. RESULTS: The development of AP was confirmed by the elevation of serum amylase levels and histopathological evidence of significant pancreatic injury in Group 2 and Group 3 rats. Both groups developed systemic organ dysfunction involving the cardiovascular system with hypotension, bradycardia, and raised lactate levels, and respiratory failure - Type 1 in Group 2 rats and Type 2 in Group 3 rats. None of the animals developed renal failure. CONCLUSIONS: Our experimental models of severe AP in rats assessed clinically relevant and translatable parameters of organ dysfunction. Although the model does not reproduce human etiologic context, it may help researchers to evaluate the benefits of therapeutic interventions targeting systemic inflammation.