DOPAMINE IN MODELS OF ALCOHOLIC ACUTE-PANCREATITIS

Acute oedematous pancreatitis and acute haemorrhagic pancreatitis were studied using the low pressure duct perfusion models of alcoholic pan creatitis in cats. After creating either form over 24 hours, each panc reas was histologically graded and assigned an inflammatory score (0-1 6; absent-severe). Urinary trypsinogen activation peptide concentratio ns were also used as a measure of severity. Using the model of acute h aemorrhagic pancreatitis, it was previously shown that low dose dopami ne (5 mug/kg.m) reduced the inflammatory score at 24 hours and that th is effect was mediated by a reduction in pancreatic microvascular perm eability acting via dopaminergic and beta adrenergic receptors. Furthe r studies were conducted and are reported here. In experiment 1 differ ent doses of dopamine in established alcoholic acute haemorrhagic panc reatitis were studied. In group 1 control cats (no dopamine), the infl ammatory score was 10.5 (interquartile range (IQR)4). In groups 2, 3, and 4, haemorrhagic pancreatitis was induced. Twelve hours later dopam ine was infused for six hours, in the doses of 2 mug/kg.min, 5 mug/kg. min, and 50 mug/kg.min respectively. The inflammatory score in group 2 was 7 (IQR 0.5, p<0.05 v group 1), in group 3 it was 7 (IQR 2, p<0.05 v group 1), and in group 4 it was 7 (IQR 4, p<0.05 v group 1). This w as matched by significantly lower levels of urinary tripsinogen activa tion peptide at 24 hours. In experiment 2 (group 5) we tried to reduce microvascular permeability further by combining dopamine with antihis tamines, but there was no improvement in the inflammatory score. As oe dematous pancreatitis is the commoner and milder form of acute pancrea titis in clinical practice, in experiment 3 we looked at the effect of dopamine in this model. In group 6 control cats (no treatment), the i nflammatory score was 7 (IQR 3, p<0.05 v group 1). In group 7 cats giv en dopamine (5 mug/kg.min for six hours) from 12 hours after the onset of acute oedematous pancreatitis, the inflammatory score was reduced to 4 (IQR 2, p<0.05 v group 6). This was matched by a significant redu ction in the 24 hour urinary tripsin activation peptide concentration.