Electron paramagnetic resonance (EPR) spectroscopy was used to investigate whether (i) the
free radicals produced in the "
stunned" myocardium (myocardium with postischemic contractile dysfunction) are derived from O2, (ii) inhibition of radical reactions improves function, and (iii) i.v. spin traps are effective. Open-chest dogs undergoing a 15-min
coronary occlusion received an i.v. infusion of the spin trap, alpha-
phenyl N-tert-butylnitrone (PBN) (50 mg/kg). In group I (n = 6), EPR signals characteristic of radical adducts of PBN appeared in the coronary venous blood during
ischemia and increased dramatically after reperfusion. In group II (n = 6), which received PBN and i.v.
superoxide dismutase (SOD; 16,000 units/kg) plus
catalase (12,000 units/kg), myocardial production of PBN adducts was undetectable during
ischemia (delta = -100%, P less than 0.01 vs. group I) and markedly inhibited after reperfusion (delta = -86%, P less than 0.001). This effect was seen at all levels of ischemic zone flow but was relatively greater in the low-flow range. In group III (n = 8), the same dosages of SOD and
catalase without PBN markedly enhanced contractile recovery (measured as systolic wall thickening) after reperfusion [P less than 0.01 at 3 hr vs. controls (group IV, n = 7)]. Systemic plasma activity of SOD and
catalase averaged 127 +/- 24 and 123 +/- 82 units/ml, respectively, 2 min after reperfusion. PBN produced no apparent adverse effects and actually improved postischemic contractile recovery in group I (P less than 0.05 at 3 hr vs. controls). This study shows that (i) SOD and
catalase are highly effective in blocking
free radical reactions in vivo, (ii) the radicals generated in the "
stunned" myocardium are derived from univalent reduction of O2, and (iii) inhibition of radical reactions improves functional recovery. The results provide direct, in vivo evidence to support the hypothesis that reactive
oxygen metabolites play a causal role in the
myocardial "stunning" seen after brief
ischemia.