Free Radical Scavengers Prevent Intestinal Ischemia-Reperfusion-Mediated Cardiac Dysfunction

Abstract

Our previous studies show that intestinal ischemia impairs cardiac function. This present study examined the contribution of oxygen-derived free radicals to cardiac dysfunction after intestinal ischemia-reperfusion in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and ligation of collateral arcades from the right colic and jejunal arteries. Controls were sham operated (Group 1, n = 10); in Group 2, 20 rats with SMA occlusion were sacrificed 2-5 hr after reperfusion without treatment. Superoxide dismutase (SOD) and catalase, scavengers of oxygen-derived free radicals which have been shown to effectively reduce ischemic injury in several models of traumatic injury, were given as 6000 units/350 g body wt either 1 min after SMA occlusion (Group 3, n = 11) or 2 min after reperfusion (Group 4, n = 10). To examine the contribution of neutrophils as a source of free radicals, additional groups of animals were treated with pentoxifylline (PTX, a methylxanthine derivative which has been shown to decrease neutrophil adherence and aggregation as well as to decrease superoxide production) either 1 min after SMA occlusion (Group 5, n = 10) or 2 min after reperfusion (Group 6, n = 10). Cardiac contractile depression occurred in the untreated ischemic group as indicated by a fall in left ventricular pressure (from 77 ± 3 to 63 ± 4 mm Hg, P < 0.01) and + dP/dt max (from 1827 ± 60 to 1558 ± 98 mm Hg/sec, P < 0.03) and - dP/dt max (from 1267 ± 57 to 953 ± 68 mm Hg/sec, P < 0.02). Contractile depression after untreated ischemia-reperfusion was confirmed by a rightward shift in left ventricular function curves and decreased responsiveness to perfusate calcium. Both free radical scavengers (SOD and catalase) and neutrophil stabilization (PTX) prevented ischemia-reperfusion-mediated cardiac dysfunction, and left ventricular function curves for these treated groups were identical to those generated by control hearts. We conclude that oxygen-derived free radicals from activated neutrophils contribute, in part, to intestinal ischemia-reperfusion-mediated cardiac dysfunction.