Edaravone attenuates ischemia-reperfusion injury by inhibiting oxidative stress in a canine lung transplantation model.
BACKGROUND
Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion (IR) injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model.


METHODS
Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin E1(PGE1)(8 microg/kg) was injected into the donor pulmonary artery (PA) before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone (10 mg/kg) and stored in the same LPD solution at a temperature of 1 degrees C for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone (10 mg/kg) at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed and histological analysis of lung tissue performed at the same time.


RESULTS
All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios (treated: (74.1 +/- 4.2)% vs control: (86.8 +/- 5.2)%, P < 0.01), MDA levels (treated: 0.50 +/- 0.08 vs. control: 0.88 +/- 0.15, P < 0.01) and MPO activity (treated: 0.23 +/- 0.05 vs. control: 0.43 +/- 0.07, P < 0.01) compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance (PVR) was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group.


CONCLUSIONS
Edaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.
Xu
Jin-zhi
JZ
Department of Thoracic Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. xujinzhi003@vip.qq.com
Shen
Bao-zhong
BZ
Li
Ye
Y
Zhang
Tong
T
Xu
Wan-hai
WH
Liu
Xiao-wei
XW
Lu
Hong-guang
HG
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D000077553:Edaravone; D015227:Lipid Peroxidation; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D009569:Nitric Oxide; D009195:Peroxidase; D000077553:Edaravone; D000983:Antipyrine