title: Inhibition of postischemic reperfusion arrhythmias by an SOD derivative that circulates bound to albumin with prolonged in vivo half-life.
abstract: Intravenously administered superoxide dismutase (SOD) rapidly disappeared from the circulation and often failed to prevent oxidative tissue injury. Thus, although superoxide radicals have been postulated to play an important role in the pathogenesis of postischemic reflow-induced tissue injury, conclusive evidence supporting this concept is lacking. We have synthesized an SOD derivative (SM-SOD) that circulated bound to albumin and accumulated in injured tissues whose local pH was decreased. Transient occlusion followed by reperfusion of the coronary artery elicited severe ventricular arrhythmias in rats. Intravenous administration of SM-SOD markedly inhibited the reflow-induced arrhythmias. SOD did not show such inhibitory effect. Kinetic analysis revealed that SM-SOD accumulated in the acidic lesion of the injured heart soon after reflow and returned to the circulation thereafter. These and other results suggest that superoxide radical and/or its metabolites would play a critical role in the pathogenesis of reperfusion arrhythmias and that SM-SOD may be useful for protecting acute myocardial injury induced by such hazardous oxygen metabolites.
authors.affiliation: Department of Biochemistry, Kumamoto University Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Morino
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D003327:Coronary Disease / Q000150:complications*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D012709:Serum Albumin; D013482:Superoxide Dismutase; D010100:Oxygen