Prevention of ischemia-reperfusion injury with a synthetic metalloprotein superoxide dismutase mimic, SC52608

Superoxide dismutase (SOD) scavenges free superoxide radicals generated during reperfusion of ischemic tissue and decreases cellular injury. A synthetic manganese-based metalloprotien superoxide dismutase mimic, SC52608 (Monsanto Co.), was tested in the isolated rabbit rectus femoris muscle flap to determine its effects on ischemia-reperfusion injury. The results of our experiments analyzing 38 isolated rectus femoris muscles in 19 New Zealand White rabbits show that administration of SC52608 at the onset of 4 hours of warm ischemia anti before reperfusion significantly increases the survival of tim muscle from 20.0±4.9 percent (control, HEPES) to 81.5 ± 4.6 percent (SC52608) (p < 0.001). It preserved functional contraction in 8 of 10 muscles; only 1 of 12 control muscles (cotrol, HEPES) had contractions (p = 0.00151). SC52608 decreased the neutrophil density from 4.63 ± 0.6 x 10⁴ cells/mm² in the control (HEPES) muscle to 2.71 ± 0.6 X 10⁴cells/mm² in muscles perfused with SC52608 (p = 0.03). The level of malonyldialdehyde decreased from 6.12 ± 0.26 nmol/gm (control, HEPES) to 4.64 ± 0.41 nmol/gm (SC52608) (p = 0.0028). Postopcrative weights of the muscles showed no statistical differenee (p = 0.14) between the controls (16.0 ± 0.9gm) and the SC52608 (18.1 ± 0.7 gm). Our investigation shows that direct intraarterial infusion of syntthetic superoxide dismutase mimic at the onset of ischemia and prior to reperfusion can reduce reperfusion injury in skeletal muscle.