Contractile and metabolic function following an ischemia-reperfusion injury in skeletal muscle: influence of oxygen free radical scavengers.
Skeletal muscle contraction and metabolism was evaluated using an in vivo, intact autoperfused canine hindlimb model during 7 hours of reperfusion following 4 hours of complete ischemia, with and without bolus administration of superoxide dismutase (SOD) and catalase (CAT) at the start of reperfusion. Contractile tension of paw dorsiflexion during reperfusion demonstrated small but statistically non-significant increases of recovery towards pre-ischemic baseline with SOD/CAT (i.e. 43% +/- 10 vs 32% +/- 9 with muscle-stimulated tetanic tension). Oxygen utilization by the hindlimb rose during reperfusion from a baseline in the control group of 2.4 +/- 0.3 ml 02/min to 5.4 +/- 1.1 during the first 10 minutes and plateaued at 3.5 +/- 1.3 by the first hour with no differences in the SOD/CAT group. Lactate clearance was prompt (increase from a pre-ischemia value of zero to 0.93 +/- .14 mM/min by 5 minutes and return to near-zero by 1 hour in controls) exhibiting no sustained anaerobic metabolism and was not affected by SOD/CAT. These finding demonstrate irreversible loss of 60-70% of skeletal muscle contraction with preservation of aerobic metabolic capacity at 225% of basal activity. Bolus administration of SOD/CAT at the start of reperfusion offered no significant improvement in metabolic or contractile function. These observations, in a model simulating the in vivo setting, necessitate evaluating alternate ischemia reperfusion conditions and modified free-radical inhibitor protocols before any clinical benefit can be assumed.
Long
J W
JW
Department of Surgery, University of Missouri Health Sciences Center, Columbia.
Laster
J L
JL
Stevens
R P
RP
Silver
W P
WP
Silver
D
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D006614:Hindlimb / Q000098:blood supply; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D005609:Free Radicals; D007773:Lactates; D019344:Lactic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen