Abstract 231: Edaravone Preserves Coronary Microvascular Nitric Oxide Availability and Myocardial eNOS Expression on Ischemia/Reperfusion Injury in Canine Heart
Background: Coronary ischemia/reperfusion (I/R) leads to a burst of free radicals generation. Nitric oxide (NO) plays an important role to maintain the tissue level perfusion after I/R. We examined the hypothesis that edaravone (3-methyl-1-phenyl-2-pyrazolin-5-on), a free radical scavenger, preserves coronary microvascular NO and myocardial eNOS expression on I/R injury.
Methods and Results: Ninety minutes LAD occlusion and reperfusion was performed in 16 open-chest dogs in the controls and group with edaravone administration (3 mg/kg, IV). Nitric oxide in coronary microvasculature (< 300 μm) was detected using NO-sensitive fluorescent dye in 15 microvessels from each ischemic (LAD) and non-ischemic (LCX) area in 6 dogs (n=3, each group) after 60 min reperfusion. Myocardial eNOS expression, collateral blood flow by microsphere and infarct-size were assessed after 5 hours reperfusion in other 10 dogs (n=5, each). Microvascular NO relative intensity in LAD area was significantly higher in edaravone group than in the controls (0.9 ± 0.1 vs 0.6± 0.1, p < 0.01; Figure⇓, left). Myocardial eNOS expression in LAD area was higher in edaravone group compared with the controls (0.8 ± 0.2 vs 0.3 ± 0.2, p < 0.05; Figure⇓, right). Edaravone shifted downward the inverse regression line between collateral blood flow and infarct-size after I/R compared with control group (control: y = −60x + 48, r = 0.96; edaravone: y = −46x + 21, r = 0.91; p < 0.01).
Conclusions: Edaravone preserves coronary microvascular NO availability and myocar-dial eNOS expression on I/R injury. These findings suggested beneficial effects of edaravone to protect coronary microvessels and myocardium during I/R.