[Cardioprotective effect of edaravone pharmacological postconditioning on acute myocardial ischemia/reperfusion injury: experiment with rats].
OBJECTIVE
To evaluate the influence of pharmacological postconditioning with edaravone, a new free radical scavenger, on myocardial ischemia/reperfusion injury and the mechanism thereof.


METHODS
Forty Wistar rats underwent ligation of the left anterior descending coronary artery (LAD) with PTCA balloon to establish ischemia/reperfusion models, with the LAD occluded for 45 min and reperfused for 180 min. The rats were randomly divided into 5 equal groups : (1) I/R group undergoing occlusion of the LAD for 45 min and reperfusion for 180 min; (2) I-postC group undergoing ischemia for 45 min, 3 cycles of balloon air relief-aeration (30s reperfusion and 30s ischemia), and then reperfusion for 180 min, (3) iA-1 group undergoing injection of edaravone, 3 mg/kg into the aorta root 1 min before reperfusion; (4) iA-2 group undergoing injection of edaravone 10 mg/kg into the aorta root 1 min before reperfusion; and (5) iV group undergoing intravenous injection of edaravone 10 mg/kg 1 min before reperfusion. Another 8 rats underwent sham operation. By the end of experiment arterial blood was collected to measure the dynamic parameters and serum biochemical markers: MB isoenzyme of creatine kinase (CK-MB), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). Then the rats were killed. The ischemic size and Infarct size of myocardium were measured by Evans blue and TTC staining respectively.


RESULTS
The myocardial infarct size and levels of serum CK-MB, MDA, and NO were all significantly reduced in the I-postC, iA-1, and iA-2 groups compared with the I/R group (all P < 0.01), and the activity levels of SOD of these groups were all enhanced (all P < 0.05). The MI size and levels of serum CK-MB and MDA of the iV group were all reduced, the activity level of SOD was enhanced compared with the I/R group (all P < 0.05), and the NO level was decreased, but not significantly.


CONCLUSIONS
Edaravone pharmacological postconditioning applied just before the onset of coronary reperfusion provides potent myocardial infarct size reduction, an effect similar to the cardio-protective effect of dynamic postconditioning. The common potential mechanism of both practices may be associated with decreasing the injury by reactive oxygen species and strengthening the resistance to oxidation stress. Intra aorta root-coronary injection may be a more effective pharmacological postconditioning pathway than intravenous pathway.
Zhang
Yong-ming
YM
General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Wang
Yu
Y
Liu
Xiu-hua
XH
Zhang
Da-wei
DW
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000097:blood* / Q000188:drug therapy*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine