Abstract
To test the possible involvement of superoxide radicals in the pathogenesis of reperfusion injury, we synthesized a superoxide dismutase (SOD) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalently linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protective effects of SM-SOD on regional cerebral blood flow, intracranial pressure, cardiac index, vascular permeability, and neurological outcome were investigated using a model of global brain ischemia in dogs. Intra-arterial injection of SM-SOD (10 mg/kg) just before reperfusion increased 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 = 0.015), 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 affecting the cardiac index. These results indicate that superoxide radicals and/or their metabolite(s) might play a critical role in the pathogenesis of reperfusion injury in the brain.
Original language | English |
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Pages (from-to) | H1708-H1715 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 264 |
Issue number | 5 33-5 |
DOIs | |
Publication status | Published - 1993 |
Keywords
- blood-brain barrier
- brain edema
- cerebral blood flow
- delayed hypoperfusion
- free radical
- global ischemia
- neurological outcome
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)