vapiprost and Edema

During revascularization of skeletal muscle lipid mediators are released that may have a role in the pathogenesis of reperfusion injury. This study investigated the efficacy of the lipid mediator antagonists U74500A (a lipid peroxidation inhibitor), GR32191 (a thromboxane A2 receptor antagonist) and SC41930 (a leukotriene B4 (LTB4) receptor antagonist) in altering muscle viability and oedema, in a rat hindlimb model of 6-h ischaemia and 4-h reperfusion. Study groups comprised normal, ischaemic (6-h ischaemia) and control rats, and animals receiving the lipid mediator antagonists. Ischaemia itself did not result in muscle oedema or necrosis but both occurred following reperfusion (P < 0.01). Muscle viability was preserved by all lipid mediator antagonists (P < 0.01 versus controls, P not significant versus normal and ischaemia), with the LTB4 receptor antagonist ameliorating limb oedema (P < 0.01 versus controls). These results demonstrate a role for lipid mediators in reperfusion injury and suggest that their antagonists might aid the management of acute limb ischaemia.

Topics: Animals; Benzopyrans; Biphenyl Compounds; Edema; Heptanoic Acids; Infarction; Ischemia; Leukotriene B4; Lipid Peroxides; Male; Muscle, Skeletal; Pregnatrienes; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane; Reperfusion Injury

The effect of a thromboxane A2 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 A2 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 A2 is an important mediator of skeletal muscle reperfusion injury and suggest that administration of a thromboxane A2 receptor antagonist may improve limb salvage rates after surgery for acute ischaemia.

Topics: Animals; Biphenyl Compounds; Disease Models, Animal; Edema; Extremities; Heptanoic Acids; Ischemia; Male; Muscles; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane; Reperfusion Injury