Role of lipid mediators in the pathogenesis of skeletal muscle infarction and oedema during reperfusion after ischaemia.
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.
Homer-Vanniasinkam
S
S
Vascular Surgical Unit, General Infirmary, Leeds, UK.
Gough
M J
MJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004487:Edema; D006538:Heptanoic Acids / Q000494:pharmacology*; D007238:Infarction / Q000517:prevention & control; D007511:Ischemia / Q000517:prevention & control; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000517:prevention & control
D001578:Benzopyrans; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D008054:Lipid Peroxides; D011281:Pregnatrienes; D017482:Receptors, Thromboxane; C059950:SC 41930; D007975:Leukotriene B4; C060013:vapiprost; C053356:U 74500A