Abstract 13283: Cardioprotective Role of Hydrogen Peroxide and Erythropoietin during Acute Coronary Occlusion in Canine Native Coronary Collateral Microcirculation in Vivo
Background: We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor and plays a crucial regulatory role in canine coronary microcirculation in vivo. However, the role of endogenous H2O2 in coronary collateral vasodilatation during myocardial ischemia before and after erythropoietin (EPO) remains to be examined. We thus examined whether endogenous H2O2 is involved in vasodilatation of native collateral microvessels during ischemia before and after EPO in vivo.
Methods: Canine subepicardial native collateral small arteries (CSA ≥100 μm) and arterioles (CA <100 μm) were observed by an intravital microscope. Experiments were performed after LAD ischemia (90 min) under the following 7 conditions (n=65); (i) control, (ii) EPO (1000 U/kg, iv), (iii) EPO+catalase (an enzyme that dismutates H2O2 into water and oxygen, 1000 U/ml, 10 min), (iv) EPO+L-NMMA (NO synthase inhibitor, 2 μmol/min for 20 min ic), (v) EPO+L-NMMA+catalase, (vi) EPO+L-NMMA+apamin+charybdotoxin [KCa channels blockers; apamin 1 μmol/min and charybdotoxin (CTX) 100 nmol/min, for 20 min ic] and (vii) EPO+wortmannin (an inhibitor of PI3 kinase, 1.5 μg/kg/min for 30 min ic).
Results: Myocardial ischemia caused significant vasodilatation in CA (19±3%) but not in CSA (2±1%) under control conditions. After EPO, the vasodilatation was significantly increased in both-sized arteries (CA 27±5%, CSA 8±2%) compared with control, and was significantly decreased by catalase in CA (13±2%). The enhancing effect of EPO was decreased by L-NMMA (−1±1%) but not by catalase (8±1%) in CSA and the inhibitory effect was more pronounced after L-NMMA+catalase (CA 9±2%, CSA -3±2%), L-NMMA+apamin+CTX (CA 7±2%, CSA −3±1%) or wortmannin (CA 7±2%, CSA −3±1%) in both-sized arteries. EPO ameliorated ischemia-induced impairment of myocardial Akt phosphorylation, which was abolished by L-NMMA+catalase or wortmannin. EPO also ameliorated oxidative stress and myocardial injury compared with control, as assessed by plasma 8-hydroxydeoxyguanosine and troponin-T in the coronary sinus, respectively.
Conclusions: EPO enhances H2O2-mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in vivo.
- Coronary microcirculation
- Endothelium-derived relaxing factor
- Ischemia reperfusion
- Myocardial infarction
- Nitric oxide
- © 2010 by American Heart Association, Inc.