Increased thromboxane A2 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, PGE₂, PGD₂, PGF_2α, TXB₂, 6-keto-PGF_1α and 5-HETE accumulated in the incubation medium were measured by radioimmunoassay.

TXB₂ 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. PGI₂ synthetase activity decreased by 40% at 30 min, with return to normal at later time points. The ratio of TXA₂/PGI₂ was significantly higher than control at 30 min and 1 wk. T e synthesis of PGE , PGD₂ 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 TXA₂ 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 B₄ and peptide leukotrienes and a potential role for these 5-lipoxygerase metabolites of arachidonate in ischemia injury to the brain and the spinal cord.