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 51Cr-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.
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
J W
JW
Horton
P B
PB
Walker
D000818:Animals; D001783:Blood Flow Velocity; D004492:Edetic Acid / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000293:injuries; D007511:Ischemia / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008638:Mesenteric Arteries / Q000502:physiology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D004492:Edetic Acid