EFFECT OF A THROMBOXANE SYNTHETASE INHIBITOR UK-38, 485 ON THE TOLERANCE OF SKIN FLAPS OF PRIMARY ISCHAEMIA

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Abstract
The harmful effects of ischaemia or skin flaps were modified using the thromboxane synthetase inhibitor UK-38,485. The epigastric island flaps of Sprague-Dawley rats (n = 288) were subjected to 10, 12 or 14 h of total pedicle occlusion, or 3, 5 or 7 h of venous occlusion of the sole vascular pedicle. Within each time period, rats received intravenous doses of either physiological saline (controls) or UK-38,485 at the beginning or end of the ischaemic episode. Flaps treated with UK-38,485 overall had a higher survival rate than control ischaemic flaps (P < 0.001). This applied both to total (arterial) ischaemia (P < 0.001) and partial (venous) ischameia (P < 0.01). There was no significant difference between treatment given at the beginning or at the end of the ischaemic episode. These results may be explained by reduced platelet aggregation and thrombosis in the microvaculature due to the lower thromboxane/prostacyclin ratios for treated flaps. The possible inter-relationship of the prostanoids with free radical mechanisms in the no-reflow phenomenon is also discussed.