Prevention of Ischemia-Reperfusion Injury with a Synthetic Metalloprotein Superoxide Dismutase Mimic, SC52608

Abstract

Superoxide dismutase (SOD) scavenges free superoxide radicals generated during reperfusion of ischemic tissue and decreases cellular injury. A synthetic manganese-based metalloprotein 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 and before reperfusion significantly increases the survival of the 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 (control, HEPES) had contractions (p = 0.0015). SC52608 decreased the neutrophil density from 4.63 +/- 0.6 x 10(4) cells/mm2 in the control (HEPES) muscle to 2.71 +/- 0.6 x 10(4) cell/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). Postoperative weights of the muscles showed no statistical difference (p = 0.14) between the controls (16.0 +/- 0.9 gm) and the SC52608 (18.1 +/- 0.7 gm). Our investigation shows that direct intraarterial infusion of a synthetic superoxide dismutase mimic at the onset of ischemia and prior to reperfusion can reduce reperfusion injury in skeletal muscle.

A reproducible method for biochemical, histological and functional assessment of the effects of ischaemia–reperfusion syndrome in the lower limbs

“…In our model, the swelling present after 24 h of reperfusion increased the upper-thigh cross-sectional area by 30%. This figure is similar to those from a rabbit experimental model 56 , in which there was a 38% in the crosssectional area after 4 h of ischemia and 24 h of reperfusion. Regarding the weight of the gastrocnemius muscle, we observed a 10% increase, while Bonheur 18 reported a 22% increase, after 3 h of ischemia and 24 h of reperfusion.…”

The Prevention of Ischemia-Reperfusion Injury in Elderly Rats after Lower Limb Tourniquet Use

“…The pathological findings, after 3 h of ischemia and 24 h of reperfusion, showed that 80.7 ± 16.4% of the fibers were damaged. These figures correlate with those reported by McCormack et al [ 67 ], with 60% of the fibers damaged after 2 h of ischemia, and by Deune et al, with 80% of the fibers damaged after 4 h of ischemia [ 68 ]. FA pre-treatment reduced the number of damaged muscle fibers in each field by 20% (64 ± 17.1 vs. 80.7 ± 16.4; p < 0.001), resulting in a reduction in damage similar to that achieved in younger rats with the same treatment (52.1 ± 20.6% vs. 65.5 ± 14.1%; p < 0.001) [ 52 ].…”

Therapeutic Interventions Against Reperfusion Injury in Skeletal Muscle

“…Free radical scavengers including allopurinol, superoxide dismutase, catalase, and dimethyl sulfoxide, etc. have been examined and shown to attenuate I/R injury in various preparations [30]. However, there are also negative reports [31,32].…”