ALBUMIN-BINDING SUPEROXIDE-DISMUTASE WITH A PROLONGED HALF-LIFE REDUCES REPERFUSION BRAIN INJURY

To test the possible involvement of superoxide radicals in the pathoge nesis of reperfusion injury, we synthesized a superoxide dismutase (SO D) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalentl y linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protectiv e effects of SM-SOD on regional cerebral blood flow, intracranial pres sure, cardiac index, vascular permeability, and neurological outcome w ere investigated using a model of global brain ischemia in dogs. Intra -arterial injection of SM-SOD (10 mg/kg) just before reperfusion incre ased reactive hyperemia (SM-SOD, 160 +/- 36 ml . 100 g-1 min-1, means +/- SD, n = 6; control, 100 +/- 34 ml . 100 g-1 . min-1, n = 6, P = 0/ 0.15), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 +/- 14 ml . 100 g-1 . min-1; control 17 +/- 6 ml . 100 g-1 . min-1, P = 0.003), vascular permeability, and neurological outcome without a ffecting the cardiac index. These results indicate that superoxide rad icals and/or their metabolite(s) might play a critical role in the pat hogenesis of reperfusion injury in the brain.