Edaravone preserves coronary microvascular endothelial function after ischemia/reperfusion on the beating canine heart in vivo.
We examined whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, exerts its protective effect on coronary microvessels after ischemia/reperfusion (I/R) in vivo. Ninety-minute coronary occlusion followed by reperfusion was performed in 16 open-chest dogs with and without edaravone administration. Coronary small artery (> or = 100 microm in size) and arteriolar (< 100 microm) vasodilation, in the presence of endothelium-dependent (acetylcholine) or -independent (papaverine) vasodilators, was directly observed using intravital microscopy before and after I/R. I/R impaired microvascular vasodilation in response to acetylcholine, whereas administration of edaravone preserved the response in microvessels of both sizes, but to a greater extent in the coronary small arteries. No significant changes were noted with papaverine administration. In the edaravone group, the fluorescent intensity from reactive oxygen species (ROS) was lower, whereas nitric oxide (NO) intensity was higher relative to controls in the microvessels of the ischemic area. In conclusion, edaravone preserves coronary microvascular endothelial function after I/R in vivo. These effects, which were NO-mediated, were attributed to the ROS scavenging properties of edaravone.
Sukmawan
Renan
R
Department of Cardiology, Kawasaki Medical School, Kurashiki, Japan. rey1708@yahoo.com
Yada
Toyotaka
T
Toyota
Eiji
E
Neishi
Yoji
Y
Kume
Teruyoshi
T
Shinozaki
Yoshiro
Y
Mori
Hidezo
H
Ogasawara
Yasuo
Y
Kajiya
Fumihiko
F
Yoshida
Kiyoshi
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004285:Dogs; D000077553:Edaravone; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008853:Microscopy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000077553:Edaravone; D000983:Antipyrine