Effect of free radical scavenging on skeletal muscle blood flow during postischaemic reperfusion.
After 6-h tourniquet ischaemia of one hindlimb in male Sprague-Dawley rats, gastrocnemius muscle blood flow was measured following 10, 120 and 240 min of reperfusion using radiolabelled microspheres. A perfusion index was calculated (experimental limb: contralateral limb) for each of these times. Comparison of perfusion indices in ten control animals (6 h ischaemia, 4 h reperfusion) with similar measurements in ten normal rats with no ischaemia and in ten ischaemic animals with the tourniquet in situ demonstrated low median (interquartile range (i.q.r.)) reflow after 10 min (control 0.12 (0.02-0.43), ischaemia 0.04 (0.00-0.07), normal 1.05 (0.68-1.18); control versus ischaemia, P not significant; control versus normal, P < 0.01). Relative reperfusion occurred at 120 min (control 0.48 (0.11-0.70), ischaemia 0.02 (0.01-0.07), normal 0.97 (0.79-1.13); control versus ischaemia, P < 0.05; control versus normal, P < 0.05) and reperfusion injury after 240 min of revascularization, with muscle blood flow being little different from that in the ischaemic group (control 0.05 (0.01-0.38), ischaemia 0.03 (0.00-0.07), normal 1.01 (0.73-1.16); control versus ischaemia, P not significant; control versus normal, P < 0.01). Two groups of 12 rats were given either intravenous superoxide dismutase and catalase or dimethylthiourea 30 min before tourniquet release, continuing throughout the period of reperfusion. Superoxide dismutase and catalase reversed low reflow, producing a median (i.q.r.) perfusion index of 0.94 (0.54-1.12) (P < 0.01 versus control, P not significant versus normal), but had no effect on relative reperfusion (0.66 (0.42-1.01), P not significant versus control) or on reperfusion injury (0.27 (0.01-0.35), P not significant versus control). In contrast, dimethylthiourea had no effect on perfusion at either 10 min (0.10 (0.03-0.15), P not significant versus control) or 240 min (0.04 (0.00-0.11), P not significant versus control), but abolished the phase of relative reperfusion at 120 min (0.04 (0.02-0.21), P < 0.01 versus control). These results indicate that, although superoxide radicals are harmful during postischaemic reperfusion, hydroxyl radicals may be beneficial.
Hardy
S C
SC
Vascular Surgical Unit, General Infirmary, Leeds, UK.
Homer-Vanniasinkam
S
S
Gough
M J
MJ
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers; D006614:Hindlimb; D008297:Male; D009132:Muscles / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D016166:Free Radical Scavengers; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea