title: Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart.
abstract: Cardioplegic arrest has been the main mechanism of myocardial protection during open-heart surgery; however, it causes myocardial injury during ischemia-reperfusion. Free radical scavengers are widely known to attenuate ischemia-reperfusion injury in various settings. We investigated the effects of edaravone, a novel free radical scavenger that was originally used for cerebral protection, on myocardial function during ischemia-reperfusion after cardioplegic arrest. Rat hearts were excised and perfused using Langendorff apparatus. The hearts were cardioplegically arrested for 90 min using St. Thomas' Hospital cardioplegic solution (ST solution) at 4 degrees C every 45 min and then reperfused for 20 min. The hearts were divided into 4 groups (n = 13 in each group). In Group ST, the hearts were arrested using the ST solution alone. In Groups L, M, and H, the hearts were arrested using the ST solution supplemented with a low-dose (1 microM), moderate dose (10 microM), and high dose (100 microM) of edaravone, respectively. Left ventricular function (+dp/dt (max)) and the levels of the cardiac enzymes released were measured before and after cardioplegic arrest. At the end of the study, the water content and the tissue oxidative stress (8-hydroxy-2'-deoxyguanosine) of the heart were measured. During reperfusion, the edaravone-treated groups showed a greater functional recovery with regard to the +dp/dt (max) (P < 0.05). The lactate level was the lowest (P < 0.01) in Group M. The water content of the hearts in the edaravone-treated groups was significantly lower (P < 0.05) than that in Group ST. Oxidative stress was significantly lower (P < 0.01) in the edaravone-treated hearts than in Group ST, and it was the lowest in Group M. The addition of edaravone to the cardioplegic solution ameliorates the impairment in myocardial function by reducing the oxidative stress after cardioplegic arrest. In this study, the maximum improvement in the myocardial function was achieved by addition of a moderate dose (10 microM) of edaravone.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, 54 Shogoin, Kawahara-machi, Sakyo-ku, Kyoto 606-8507, Japan. yamakazu@kuhp.kyoto-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Senri
authors.initials: S
authors.lastname: Miwa
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nemoto
authors.forename: Wnimunk
authors.initials: W
authors.lastname: Oriyanhan
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Takaba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saji
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishina
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine