Role of thromboxane A2 in muscle injury following ischaemia.
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.
Homer-Vanniasinkam
S
S
Vascular Surgical Unit, General Infirmary at Leeds, UK.
Crinnion
J N
JN
Gough
M J
MJ
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema; D005121:Extremities / Q000098:blood supply*; D006538:Heptanoic Acids / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D017482:Receptors, Thromboxane; C060013:vapiprost