Increased thromboxane A 2 and 5-HETE production following spinal cord ischemia in the rabbit

Abstract

Ischemia was induced for 25 min in the spinal cord of rabbits followed by a long term period of recirculation. At various time points of recirculation (5, 30 min, 4, 18 hr and 1 wk) slices were taken from the ischemic region and incubated for 45 min in Krebs-Ringer solution. The levels of the eicosanoids, PGE 2, PGD 2, PGF 2α, TXB 2, 6-keto-PGF 1α and 5-HETE accumulated in the incubation medium were measured by radioimmunoassay. TXB 2 release was found to be increased at an early (5 min) and late (1 wk) period of reperfusion. A seven-fold increase in the release of 5-HETE was found 5 min after reperfusion that tended to stay elevated at 18 hr and 1 week of recirculation. PGI 2 synthetase activity decreased by 40% at 30 min, with return to normal at later time points. The ratio of TXA 2/PGI 2 was significantly higher than control at 30 min and 1 wk. T e synthesis of PGE , PGD 2 and PGF 2α was maintained at normal levels throughout the complete course of reperfusion. No changes in eicosanoid synthesis were noted in remote spinal cord regions. The significant increase of TXA 2 synthesis at 5 min and 1 wk of reperfusion may point to a role of this arachidonate metabolite in the acute events and in the later stages of neurological dysfunction. The enhanced release of 5-HETE, a metabolite of 5-HETE, suggest an enhanced formation of leukotriene B 4 and peptide leukotrienes and a potential role for these 5-lipoxygerase metabolites of arachidonate in ischemia injury to the brain and the spinal cord.