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.

Mitochondrial Involvement in Cardiac Apoptosis During Ischemia and Reperfusion: Can We Close the Box?

“…Rajesh et al (2003) demonstrated that the MPT inhibiting property of edaravone was specific for the attenuation of cytochrome c release, thereby pathological apoptosis was decreased in rat hearts in vivo [151]. Recently, edaravone has demonstrated to be equally useful as a cardioplegic adjuvant for heart preservation [152].…”

Beyond neurological disease: New targets for edaravone (Review)

“…Animal experiments have revealed protective effects of edaravone against myocardial I/R injury in an AMI model and in a transplantation model (19,20). Edaravone reduced the myocardial necrotic area following myocardial I/R in rats (21) and in rabbits (22).…”

“…Cardioplegic arrest is the main technique used for myocardial protection during open-heart surgery; however, it can lead to myocardial injury during reperfusion (20). Free radical scavengers attenuate I/R injury in various settings (20), and the addition of edaravone to the cardioplegic solution attenuated myocardial dysfunction following cardioplegic arrest in rats by suppressing oxidative stress (20).…”

“…Free radical scavengers attenuate I/R injury in various settings (20), and the addition of edaravone to the cardioplegic solution attenuated myocardial dysfunction following cardioplegic arrest in rats by suppressing oxidative stress (20). Edaravone also exerted cardioprotective effects in a pig heart transplantation model by inhibiting lipid peroxidation (19).…”

Beyond free radical scavenging: Beneficial effects of edaravone (Radicut) in various diseases (Review)

“…Furthermore, in rats, edaravone prevented lethal reperfusion ventricular tachyarrhythmias and deteriorated cardiac function with ischemia and I/R injuries through inhibition of lipid peroxidation by scavenging free radicals (36). The addition of edaravone to cardioplegic solution ameliorated myocardial functional impairment by reducing oxidative stress after cardioplegic arrest in rats as well (37). Edaravone reduced myocardial oxidative stress overload with DNA damage, decreased myocardial protein carbonyl contents, the myocardial thiobarbituric acid reactive substance products, the formation of hydroxyl radicals and cytotoxic activities of lymphocytes in rats with EAM.…”