Reversal of the post-ischaemic changes in skeletal muscle blood flow and viability by a novel inhibitor of lipid peroxidation.
The role of a novel inhibitor of lipid peroxidation (U74500A) in modifying post-ischaemic changes in skeletal muscle blood flow, viability and oedema has been investigated in a rat model of 6 h unilateral hindlimb ischaemia followed by 4 h reperfusion. During reperfusion, gastrocnemius muscle blood flow (GMBF) was measured (radiolabelled microspheres) at 10, 120 and 240 min and a perfusion index (PI) calculated between the reperfused and contralateral normal limb. Muscle viability (GMV--nitroblue tetrazolium) and oedema (wet:dry weight ratio, reperfused: contralateral limb) were assessed after 4 h reperfusion. GMBF in untreated controls, compared to normal animals, demonstrated a triphasic pattern of low reflow at 10 min [PI 0.08 (0.01-0.13) vs. 1.05 (0.68-1.18), p < 0.01], relative reperfusion at 120 min [PI 0.29 (0.09-0.59) vs. 0.97 (0.79-1.13), p < 0.05] and reperfusion injury at 240 min [PI 0.05 (0.01-0.14) vs. 1.01 (0.73-1.16), p < 0.01] with a median GMV at 240 min of 52.9% (33.3-61.4), p < 0.01 vs. normals and 6 h ischaemia alone (GMV 100% in all limbs) and an oedema index of 1.23 (1.09-1.37 p < 0.01 vs. normal. In contrast, rats receiving U74500A (2 mg/kg i.v. infusion commencing 30 min prior to revascularisation) exhibited enhanced GMBF throughout reperfusion [PI 10 min: 3.26 (2.56-3.63); 120 min: 2.03 (1.73-2.25); 240 min: 2.13 (1.75-2.44), p < 0.01 vs. controls and normals] with complete muscle salvage [GMV 100% in all reperfused muscles, p < 0.01 vs. controls, not significant (NS) vs. normals and 6 h ischaemia].(ABSTRACT TRUNCATED AT 250 WORDS)
Homer-Vanniasinkam
S
S
Vascular Surgical Unit, General Infirmary, Leeds, U.K.
Hardy
S C
SC
Gough
M J
MJ
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007262:Infusions, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D009132:Muscles / Q000098:blood supply*; D011281:Pregnatrienes / Q000627:therapeutic use*; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*; D014022:Tissue Survival / Q000187:drug effects*
D000975:Antioxidants; D008054:Lipid Peroxides; D011281:Pregnatrienes; C053356:U 74500A