ADJUNCTIVE VASODILATOR THERAPY IN THE TREATMENT OF MURINE ISCHEMIA

Potent vasoconstrictors such as angiotensin II and vasopressin have be en implicated as mediators of persistent vasoconstriction after revers ible superior mesenteric artery (SMA) occlusion. Neither captopril (CA P), an angiotensin-converting enzyme (ACE) inhibitor, nor papaverine ( PAP), a vasodilator, has proven effective in reversing this vasoconstr iction when employed singly. The present study examined the combined e ffect of these agents in reducing mortality in a murine model of acute mesenteric ischemia. The SMAs of 106 adult male Sprague-Dawley rats w ere totally occluded for 85 minutes. Test agents were given intravenou sly at reperfusion over a 90-minute period. Survival rates were assess ed at 48 hours. CAP was given as a single bolus (0.3 mg/kg) and PAP (0 .5 mg/kg/h) as an infusion. Aortic and SMA blood flows were measured p retreatment and posttreatment in a separate group of 19 animals treate d with CAP and PAP as single agents. Chi2 analysis and analysis of var iance were used to test differences with p less-than-or-equal-to 0.05 accepted as significant. PAP alone as an adjunct resulted in a signifi cant increase in 48-hour survival (57% versus 19%, p less-than-or-equa l-to 0.005). PAP in combination with CAP produced the best outcome in this model (87% versus 19%, p less-than-or-equal-to 0.005). Aortic blo od flow decreased, whereas SMA blood flow increased after treatment bo th with CAP and with PAP, but not significantly. The combination of an intravenously administered vasodilator with either glucagon or an ACE inhibitor was the most effective adjunctive therapy in this mesenteri c ischemia model. There was no evidence that an inotropic effect, rath er than SMA vasodilation, was the responsible mechanism of action.