Hemodynamic effects and the effective treatment of naloxone on experimental acute pancreatitis in dogs.

Dog model of acute pancreatitis, induced by intrapancreatoductal injection of fresh trypsin-bile mixture, was used to investigate the effects of naloxone on hemodynamic changes in acute pancreatitis. In the control group, acute pancreatitis was induced and characterized hemodynamically by the decrease in maximum positive and negative dP/dt (+/- dP/dtmax), cardiac output (CO) and cardiac index (CI), and increase in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVP), as well as early reduction of pancreatic blood flow (PBF). In the naloxone treated group, naloxone was given intravenously 10 minutes after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 hours). It was found that naloxone significantly increased PBF and the +/- dP/dtmax effectively prevented the significant decrease in CO, CI and increase in PVR, SVR observed in untreated acute pancreatitis; and significantly reduced the severity of pancreatitis, as assessed by both histological staging and mortality rate. These results suggest that naloxone appears to limit the progression from edematous to hemorrhagic pancreatitis through preserving PBF and improving systemic hemodynamics at the early phase of acute pancreatitis; hence the hypothesis that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis.