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 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.
Deune
E G
EG
Division of Plastic Surgery, Washington University School of Medicine, St. Louis, Mo., USA.
Koopman
R
R
Smith
M E
ME
Hong
S P
SP
Ozbek
M R
MR
Khouri
R K
RK
D000818:Animals; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013524:Surgical Flaps
D016166:Free Radical Scavengers; D009942:Organometallic Compounds; C089774:SC 52608