Recombinant human manganese superoxide dismutase attenuates early but not delayed skeletal muscle dysfunction following reperfusion injury.
OBJECTIVE
to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in prevention of early and late skeletal muscle ischaemia-reperfusion injury mediated by superoxide (O2-). Design : randomised controlled trial.


METHODS
seventy-two Sprague-Dawley rats (250-350 g) randomised to receive either 7.5 mg/kg of rhMnSOD or saline. Four hours of ischaemia was induced in the cremaster muscle by dissecting free and clamping its vascular supply. Cremaster muscle contractile function was assessed following 90 minutes, 24, 48 hours and one week of reperfusion. Electrophysiological muscle function was assessed using electrical field stimulation in an organ bath system.


RESULTS
muscle function in the untreated groups following ischaemia reperfusion was significantly reduced at 90 minutes, 24, 48 hours and one week of reperfusion (p <0.05). rhMnSOD significantly protected and maintained normal muscle function at 24 and 48 hours (p <0.001). However at one week of reperfusion there was a reduction in function of the treated muscle, such that there was no significant difference between treated and untreated muscle at this point in time.


CONCLUSIONS
these data demonstrate that skeletal muscle dysfunction after ischaemia reperfusion injury is attenuated at 24 and 48 hrs of reperfusion by the superoxide scavenger rhMnSOD. This protective effect is not maintained after seven days of reperfusion.
Bowler
D J
DJ
Department of Surgery, Beaumont Hospital, Dublin, 9, Ireland.
McLaughlin
R
R
Kelly
C J
CJ
O'Farrell
D A
DA
Moran
Bouchier-Hayes
D
D
D000818:Animals; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D011994:Recombinant Proteins; D013481:Superoxides; D013482:Superoxide Dismutase