Endothelial injury from a circulating mediator following rat liver ischemia.
Ischemia-reperfusion to the liver results in increased microvascular permeability in a nonischemic lung. We hypothesized that a circulatory mediator released from ischemic liver contributed to endothelial cell (EC) damage. Isolated rat livers, made ischemic for 2 h, were reperfused for 10 min. Bovine ECs were incubated for 5 h with pooled liver effluent collected before ischemia (Baseline) or after 10 min of reperfusion (Reperfusion). In the Reperfusion group, there was increased endothelial cell injury, as determined by release of 8-[14C]adenine, (39 +/- 2%) compared to the Baseline group (22 +/- 2%). Permeability of ECs to rhodamine B-labeled dextran (70,000 Mr) was also increased in the Reperfusion group by 54 +/- 9%. There was no significant attenuation in EC injury following incubation with reperfusion effluent stored for 24 h, supplementation with antioxidants (superoxide dismutase + catalase), or inhibition of xanthine oxidase with allopurinol or tungstate. We conclude that the reperfused liver releases a long-lived circulatory mediator of EC injury, which may produce the clinical microvascular injury observed following hepatic ischemia. The mechanism of injury in our model is independent of oxidants or oxidants generated from the circulating xanthine oxidase released from reperfused ischemic liver.
Tan
S
S
Department of Pediatrics, University of Alabama at Birmingham, USA.
McAdams
M
M
Royall
J
J
Freeman
B A
BA
Parks
D A
DA
D000225:Adenine / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability; D003911:Dextrans; D004730:Endothelium, Vascular / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D005609:Free Radicals; D007511:Ischemia / Q000473:pathology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012235:Rhodamines; D013482:Superoxide Dismutase / Q000494:pharmacology; D017973:Tungsten Compounds / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D003911:Dextrans; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D005609:Free Radicals; D011480:Protease Inhibitors; D012235:Rhodamines; D017973:Tungsten Compounds; C051311:rhodamine dextran; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000225:Adenine; C045951:tungstate