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.
Horton
J W
JW
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
Walker
P B
PB
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