Study On The Cardioprotection Of Ischemic Postconditioning And Adenosine Postconditioning In Cadaver Donor Rats With Warm Ischemia

Background:With the development of transplantation,researchers must face a global problem—the shortage of donors.In order to enlarge the donor pool,some of them turn to non-heart-beating donors(NHBD) and attempt to use cadaver non-beating heart(CNBH)in the heart trans-plantation. Now they think the CNBH received from those who die from acute hemorrhagic shock may be useful.Because none preconditioning methods can be used before the heart stop beating.So we have to try some postconditioning methods to attenuate the warm ischemia and ischemia-reperfusion injury,and to improve the cardiac function after heart transplantation.Objective:Firstly we try to set up a cervical heterotopic heart trans-plantation in warm ischemic death rats.Then we use ischemic postcondi-tioning and adenosine postconditioning methods in the transplantation. 24 hours after transplantation we detect the change of the graft.Based on the data we evaluate the effects of these two methods and try to find the involving mechanisms.Methods:The experiment includes three parts.Part one:To set up a model of cervical heterotopic heart transplanta-tion in rats.Part two:Study on the cardioprotection of ischemic postconditioning in cadaver donor rats with warm ischemia.Rats were randomly divided into seven groups.C group—control group.I₅,I₁₅,I₃₀group—simple warm ischemia group,CNBH received from the cadaver rats which were die from acute hemorrhagic shock and the warm ischemic durations are 5 min,15min and 30min separately.Then the CNBH were used to heart transplantation.P₅,P₁₅,P₃₀group—ischemic postconditioning group, after the heart transplanted as the simple warm ischemia group,the donor hearts were treated with ischemic postconditioning.24 hours after transplantation we detect the change of the grafts including pathologic damages,ATP,SOD,MDA,NF-κB mRNA,TNF-αIL-6,apoptosis level,Bcl-2 and Bax proteins.Part three:Study on the cardioprotection of adenosine postconditioning in cadaver donor rats with warm ischemia.Rats were randomly divided into seven groups.C group—control group.I₅,I₁₅,I₃₀ group—simple warm ischemia group,CNBH received from the cadaver rats which were die from acute hemorrhagic shock and the warm ischemic durations are 5 min,15min and 30min separately.Then the CNBH were used to heart transplantation.A₅,A₁₅,A₃₀group—adenosine postconditioning group,the CNBH were received as mentioned and treated with adenosine postconditioning before heart transplantation.24 hours after transplantation we detect the change of the grafts including pathologic damages,ATP,SOD,MDA,NF-κB mRNA, TNF-αIL-6,apoptosis level,Bcl-2 and Bax proteins.Result:1,The CNBH within 30min warm ischemia and 1h cold ischemia can be transplanted successfully.2,With the prolonged warm ischemia duration,the ischemia/reper-fusion injury became more severe and the pathologic damage became worse.But at the same time point,compared with the simple warm ischemia group,the myocardial injury of the ischemic postconditioning group and the adenosine postconditioning group were attenuated. 3,At the same time point,compared with the simple warm ischemia group,the ischemic postconditioning group and the adenosine post-conditioning group can increase ATP and SOD in myocardial tissue, decrease MDA,NF-κB mRNA,TNF-α,IL-6.In addition,the decrease of apoptosis level,up-regulation of Bcl-2 protein and down-regulation of Bax protein can be detected in these two groups.Conclusion:1,The CNBH within 30min warm ischemia and 1h cold ischemia can be transplanted successfully.2,Ischemic postconditioning and adenosine postconditioning can protect the graft from ischemia-reperfusion injury in cadaver donor rats with warm ischemia.3,The involving mechanisms may include that ischemic postcondi-tioning and adenosine postconditioning can improve myocardial energy metabolism,attenuate lipid peroxidation injury,suppress the expression of NF-κB mRNA,decrease the inflammatory damage of TNF-αand IL-6, up-regulation of Bcl-2 protein and down-regulation of Bax protein which lead to the shortage of myocardial cell apoptosis.New ideas:1,The study innovatively introduced the conception of postcondi-tioning into the area of heart transplantation.2,We study on the cardioprotection of ischemic postconditioning in cadaver donor rats with warm ischemia for the first time.The similar researches were not reported.3,We study on the cardioprotection of adenosine postconditioning in cadaver donor rats with warm ischemia for the first time.The similar researches were not reported.Limitation:For the restriction of funds and equipments,we cannot evaluate the cardiac function of the graft,the detected data were limited and the observing duration was not long.