Reactive
oxygen/
nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous
hydrogen peroxide through dismutation of
superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional
ischemia reperfusion. Heart rate, arterial blood pressure, blood flow,
infarction, and activities of mitochondrial
NADH dehydrogenase and
cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitricoxide synthase knock-out (eNOS(-/-)) mice treated with
phosphate-buffered saline (PBS),
superoxide dismutase mimetic (SOD(m))
M40403 [a
manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic
superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [
EUK134,
manganese 3-methoxy N,N(1)-bis(salicyclidene)ethylenediamine
chloride], and SOD(m) plus
glibenclamide to study the protective effect of
hydrogen peroxide via dismutation of
superoxide on the activation of sarcolemmal
potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SOD(m),
EUK134, and SOD(m) +
glibenclamide protected mitochondrial
enzyme activities, reduced
infarct size, and suppressed the postischemic hyperoxygenation. In particular, in the SOD(m)-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous
hydrogen peroxide but not
nitric oxide formation as it appeared in both WT and eNOS(-/-) mice. Blood flow and rate pressure product were higher in the SOD(m) group than in other groups, which contributed to the transient
oxygen peak. Thus, SOD mimetics protected mouse heart from
superoxide-induced
reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous
hydrogen peroxide via dismutation of
superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal
ATP-sensitive potassium channels.