ROLE OF THROMBOXANE A(2) IN MUSCLE INJURY FOLLOWING ISCHEMIA

The effect of a thromboxane A(2) receptor antagonist (GR32191) on gastrocnemius muscle blood flow, oedema and viability was assessed in a rodent model of 6-h unilateral hindlimb ischaemia and 4-h reperfusion, and the results compared with those in control and normal groups, and in animals undergoing 6-h ischaemia alone. Control animals demonstrated reduced muscle blood flow throughout reperfusion (at 10 min, P < 0.01 versus normal, P not significant versus ischaemia; at 120 min, P < 0.05 versus normal and ischaemia; at 240 min, P < 0.01 versus normal, P not significant versus ischaemia), and the development of muscle oedema (P < 0.01 versus normal and ischaemia) and muscle necrosis (P < 0.01 versus normal and ischaemia). In contrast, the thromboxane A(2) receptor antagonist enhanced muscle blood flow (at 10 min, P < 0.01 versus control; at 120 min, P < 0.05 versus control; at 240 min, P < 0.01 versus control) and preserved muscle viability (P < 0.01 versus control; P not significant versus normal and ischaemia). These results indicate that thromboxane A(2) is an important mediator of skeletal muscle reperfusion injury and suggest that administration of a thromboxane A(2) receptor antagonist may improve limb salvage rates after surgery for acute ischaemia.