OXYGEN RADICALS, LIPID-PEROXIDATION, AND PERMEABILITY CHANGES AFTER INTESTINAL ISCHEMIA AND REPERFUSION

This study examined the effects of a 21-aminosteroid, U-74389, on lipid peroxidation [determined by plasma and tissue malondialdehyde (MDA) levels], intestinal permeability (plasma-to-luminal clearance of Cr-51-labeled EDTA), and intestinal blood flow (laser Doppler) during and after intestinal ischemia [superior mesenteric artery (SMA) and collateral vessel occlusion for 20 min with atraumatic clip]. Untreated ischemia increased EDTA clearance (from 0.050 +/- 0.005 to 0.169 +/- 0. 040 ml . min-1 . 100 g-1; n = 16, P = < 0.05), reduced SMA flow 88% (P < 0.05), and increased plasma MDA (0.340 +/- 0.120 to 4.030 +/- 0.86 nmol/ml; n = 8, P = 0.01); 2 h of reperfusion further increased EDTA clearance (0.323 +/- 0.060 ml.mg-1.100 g-1). EDTA clearance remained unchanged from baseline throughout the experimental period in sham ischemic rats (n = 12, 0.060 +/- 0.006 ml . min-1 . 100 g-1). Aminosteroid treatment at ischemia (n = 10) or with reperfusion (n = 11) returned EDTA clearance to near baseline (baseline 0.071 +/-0.023; reperfusion 0.091 +/- 0.014 ml . min-1 . 100 g tissue-1) and reduced the ischemia-reperfusion-associated rise in tissue MDA. Two hours after reperfusion, SMA blood flow was above baseline values in all experimental groups. Our data suggest that oxygen-derived free radicals produced during intestinal ischemia and reperfusion contribute to 1) lipid peroxidation of cell membranes and 2) increases in intestinal mucosal permeability, potentiating bacterial translocation and sepsis.