Low dose dopamine protects against hemorrhagic pancreatitis in cats

Abstract

Acute hemorrhagic pancreatitis (HP) is probably associated with decreased blood flow in its early phases, as well as with an increase in microvascular permeability. Dopamine (DOP; 5 μg/kg-min) is a splanchnic vasodilator, and also has β-adrenergic effects that can prevent increases in microvascular permeability. We hypothesized that low dose dopamine might have beneficial effects on both blood flow and microvascular permeability, thus ameliorating the severity of the disease. We studied its actions in an animal model of HP. In anesthetized cats, intragastric ethanol (20 ml/40% solution) rendered the main pancreatic duct permeable to pancreatic enzymes. Then the duct was perfused from tail to head with 0.5 ml of activated pancreatic enzymes for 1 hr. To create HP, 16,16-dimethyl prostaglandin E 2 (2 μg/kg-hr, iv) was given for 2 hr to increase blood flow and microvascular permeability. Seven of eight cats developed HP in 24 hr. Control cats received no additional drugs. Two experimental groups received DOP (6 hr infusion) begun either (1) at the onset of enzyme perfusion or (2) 12 hr later. Each pancreas was examined after 24 hr and graded (1–4) histologically for edema, hemorrhage, polymorphonuclear cell infiltrate, and architectural loss. An inflammatory score (IS) from 0 to 16 was thus created (higher scores = greater damage). The results showed an IS of 10.9 ± 1.8 for the controls, 3.3 ± 0.5 for the immediate treatment group, and 7.2 ± 1.8 for the delayed treatment group. Both treated groups had a significantly better IS ( t tests, P < 0.001 and P < 0.01, respectively). We concluded that low dose DOP was effective treatment for HP even when it was given up to 12 hr after the insult.