Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury.
Mucosal arachidonic acid metabolism was examined after 3 h of ischemia and 1 h of reperfusion in isolated ileal segments in the dog. The cyclooxygenase products thromboxane B2, 6-ketoprostaglandin F1 alpha, and prostaglandin E2 increased by 365%, 97%, and 158%, respectively, after ischemia and reperfusion but were not altered after 3 h of ischemia alone. The potent chemotactic lipoxygenase product leukotriene B4 (LTB4) increased by 687% after ischemia and reperfusion and was not affected by ischemia without reperfusion. In addition, tissue production of the thiol ether leukotrienes (LTC4, LTD4, and LTE4) increased threefold after ischemia and reperfusion. Quantitation of regionally isomeric hydroxy acids produced from arachidonate revealed a 300% increase in 12-hydroxyeicosatetraenoate (12-HETE) after intestinal ischemia and reperfusion without a change in other isomers (15-HETE and 5-HETE). Stereochemical analysis of 12-HETE demonstrated exclusive synthesis of the S-enantiomer. A significant and time-dependent decrease in intestinal blood flow also occurred during reperfusion. Administration of the dual cyclooxygenase-lipoxygenase synthesis inhibitor BW755C (1 mg/kg ia) did not alter time-dependent decreases in blood flow and failed to inhibit eicosanoid synthesis. Histologic examinations of intestinal samples revealed significant mucosal damage associated with ischemia alone and ischemia after reperfusion. This study indicates that intestinal ischemia-reperfusion injury is associated with dramatic alterations in mucosal production of vasoactive eicosanoids and with changes in blood flow that occur during reperfusion but not during ischemia alone. These events may be involved in the pathology characteristic of this injury.
Mangino
M J
MJ
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Anderson
C B
CB
Murphy
M K
MK
Brunt
E
E
Turk
J
J
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D004285:Dogs; D006893:Hydroxyeicosatetraenoic Acids / Q000302:isolation & purification / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000378:metabolism*; D013237:Stereoisomerism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D011453:Prostaglandins; D016718:Arachidonic Acid