The Protective Effect Of Edaravone On Lung Ischemia Reperfusion Injury In Rabbits

Objectives: More and more patients with terminal cardiopulmonary diseases are benefiting from open heart surgery, organ transplantations and cardiopulmonary-cerebral resuscitations. However lung injury induced by ischemia-reperfusion is still the main cause of early graft failure after lung transplantation, which may result from oxygen-free radicals, inflammatory cytokine production, and polymorphonuclear leukocyte accumulation into the interstitium, resulting in severe lung edema and respiratory distress. A newly synthesized free-radical scavenger and potent antioxidant, edaravone (3-methyl-l-phenyl-2-pyrazolin-5-l), has recently been shown to have protective effect against ischemia-reperfusion injury in many tissues. The purpose of this study was to investigate whether or not edaravone is effective in reducing lung ischemia-reperfusion injury in rabbits.Methods: 24 rabbits were randomly divided into three groups: (1) the control group(group C , n=8): received sternotomy only and no ischemia; (2) the ischemia / reperfusion group(group I/R, n=8): the left lungs of rabbits were rendered ischemia by ligating the left pulmonary hili for 60 minutes followed by 60 minutes reperfusion; (3) theedaravone group(group E, n=8): the left lungs were rendered ischemia for 60 minutes followed by 60 minutes reperfusion, edaravone 10mg/kg was administered intravenously 5 minutes prior to ischemia. Blood MDA and SOD were measured, protein concentrations, WBC count, PMN pencentage in broncho-alveolar lavage fluid were determined, the left lung dry-to-wet weight ratio compared, samples of left lung tissue were sent for histologic evaluation.Results 1.MDA levels in the blood serum of control group, edaravone group and I/R group were 5.31±0.6nmol/ml, 6.02±0.77nmol/ml and 8.17±1.17nmol/ml,respectively;blood MDA level of I/R group was significantly higher than that of the control group and edaravone group (P<0.01) ;there was no significant difference between the control group and edaravone group(P>0.05). 2. Serum SOD activity of control group, edaravone group and I/R group were 416.27±15.8 U/ml, 402.51±11.93 U/ml and 308.87±22.01 U/ml, respectively; Serum SOD activity of I/R group was significantly lower than that of the control group and edaravone group (P<0.01) ;there was no significant difference between the control group and edaravone group(P>0.05). 3. Protein concentrations, WBC count, PMN pencentage in broncho-alveolar lavage fluid of of I/R group was significantly higher than that of the control group and edaravone group (p<0.01) ;there was no significant difference between the controlgroup and edaravone group(P>0.05). 4. Left lung dry-to-wet ratio of of I/R group(0.1887±0.002) was significantly lower than that of the control group (0.203±0.002) and edaravone group (0.1968±0.002)(P<0.01) ; there was no significant difference between the control group and edaravone group(P>0.05). 5. Histologic evaluations revealed mild alterations in alveolar structure, less white blood cell infiltration and less interstitial edema.Conclusions This study suggests that intravenous edaravone prior to ischemia attenuates lung ischemia reperfusion injury in rabbits through its radical scavenging and antioxidant action.