Abstract 3928: Crucial Role of Hydrogen Peroxide as an Endogenous EDHF during Acute Coronary Occlusion and Injection of Erythropoietin in Canine Coronary Native Collateral Microcirculation in Vivo
Background: We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in canine coronary microcirculation in vivo. The aim of this study was to examine the role of H2O2 as an EDHF during acute coronary occlusion and injection of erythropoietin (Epo) in the vasodilatation of collaterals in canine coronary microcirculation in vivo.
Methods: Canine subepicardial collateral small coronary arteries (CSA, ≥100 μm) and arterioles (CA, <100 μm) were continuously observed by a microscope during acute coronary occlusion under cyclooxygenase blockade (ibuprofen). Native collateral microvessels were visually traced between the left anterior descending (LAD) and left circumflex coronary artery using injection of indocyanine green dye. Experiments were performed after LAD occlusion under the following 7 conditions (n=5 each); control, low-dose and high-dose Epo (L-Epo 100 and H-Epo 1000 IU/kg), catalase (a decomposer of H2O2)+H-Epo, NO synthase inhibitor (L-NMMA)+ catalase+H-Epo, L-NMMA+tetraethylammonium (TEA, KCa channels blocker)+ H-Epo and wortmannin (WTMN, PI3-kinase inhibitor)+ H-Epo.
Results: CA dilated (16±3% vs. baseline) after 80 min of LAD occlusion, but CSA did not (1±1%). The coronary vasodilatation was significantly increased after H-Epo in both-sized arteries (CSA 6±1%, CA 22±4%) compared with control and L-Epo (CSA 2±1%, CA 18±3%). Catalase+H-Epo significantly decreased the vasodilatation in CA (12±2%). The vasodilatation was markedly attenuated after L-NMMA+catalase±H-Epo (CSA −4±1% and CA 6±1% vs. control, both P<0.01), L-NMMA+TEA+H-Epo (CSA −5±1% and CA 6±1%, both P<0.01) and WTMN+H-Epo (CSA −5±1% and CA 6+1%, both P<0.01) in both-sized arteries. H-Epo group after ischemia/reperfusion (90 min/5 hrs) significantly improved CPK-MB (29+8 ng/ml, P<0.05) compared with control (77±24 vs. baseline 10±1, P<0.05) and L-Epo (43±10, P<0.05). CPK-MB was significantly increased in L-NMMA+catalase+H-Epo (95±10), L-NMMA+TEA+H-Epo (99±10) and WTMN+H-Epo (131±10) (all P<0.05).
Conclusions: H2O2 plays an important role in the dilatation of collaterals after coronary occlusion and injection of Epo in canine coronary microcirculation in vivo.