Mechanism Research On The Preservation Effect Of Ultra-cold Preservation Method On Mice Donor Hearts

Purpose:As the population aged,the incidence of hypertension,coronary atherosclerotic heart disease,obesity and other diseases has increased significantly,leading to continuous rising prevalence of heart failure.It is estimated that by 2030,the prevalence of heart failure will increase to 46%,which will remain the leading cause of death worldwide.For patients with end-stage heart failure,medical drug therapy and mechanical circulatory support fail to improve the long-term survival rate.At the same time,with the continuous development of current heart transplantation surgical technology,heart preservation methods,and postoperative immunotherapy,heart transplantation remains the best treatment plan for end-stage heart failure.The static cryopreservation is currently the most conventional method of preservation of isolated donor hearts.In order to improve the preservation quality of donor hearts,increase preservation time,and prolong the survival time of patients after transplantation,we adopted a new method.The ultra-cold preservation method is used to preserve isolated mouse heart.It is observed that the new preservation method is compared with the conventional UW liquid preservation method.What are the advantages of the preservation effect?Methods:C3H/HeSlc(C3H)male mice were randomly divided into three groups to establish a mouse heterotopic heart transplantation model.Group A:non-preservation group.Immediate transplantation was performed when the mice donor heart was removed,with no special treatment administered.Group B:conventional UW solution preservation group.The donor hearts were preserved in UW protection solution,and transplantation was performed with donor hearts being stored at low temperature(4℃)for 24 hours.Group C:Ultra-cold preservation solution group.The donor hearts were preserved in the ultra-cold preservation solution,and transplantation was performed with donor hearts after storing at-8℃ for 24 hours.Results:Compared with the conventional UW solution preservation group,the ATP concentration of heart tissue preserved in the ultra-cold group was higher(ultra-cold group:1.78 1±0.2598μmol/g;UW group:0.7604±0.1386μmol/g,p<0.0001);The glycogen components in the ultra-cold preservation group were better preserved;The inflammatory factors in the ultra-cold preservation group were reduced,and the number of heart tissue infiltrating neutrophils in the ultra-cold preservation group was reduced,(ultra-cold preservation group:7.733±2.852,and conventional UW preservation group 26.57 ±4.847,p<0.0001);the level of oxidative stress index(TBARS)in the ultra-cold preservation group is also lower than that of the conventional UW preservation group(ultra-cold preservation group:3.405±0.4234μM,conventional UW solution preservation group:5.084±0.3873μM,p<0.0001);At the postoperative hour 24(POH24)after 24-hour preservation,for myocardial apoptosis,the number of TUNEL-positive cardiomyocytes in the ultra-cold preservation group was significantly less than that in the conventional UW solution preservation group(ultra-cold preservation group:3.174 ±0.6128%,conventional UW solution preservation group:15.66±2.941%,p<0.0001);The serum levels of myocardial injury markers in the ultra-cold preservation group were lower than those in the UW solution preservation group(creatine phosphokinase:172.7±31.35 U/L,UW preservation group:335.8±39.73 U/L,0.0001;Hydrogenase:1079±114.5 U/L,UW preservation group:1990±458.3 U/L,p<0.001);The water content of myocardial tissue in the ultra-cold preservation group was also lower than that of the conventional UW preservation group(ultra-cold preservation group:76.19±0.95 95,conventional UW preservation group:78.36±0.8969,p=0.0017<0.01).Conclusion:The ultra-cold preservation method greatly prolongs the preservation time and improves the results after transplantation by reducing the ATP metabolism,protecting the myocardial structure,decreasing myocardial ischemia-reperfusion injury,oxidative stress-related injury and cardiomyocyte apoptosis.Therefore,the development of ultra-cold preservation technology will increase the utilization rate of donor hearts and bring better results after transplantation,which is expected to become a new technology that overcomes the bottleneck of the existing technology of organ preservation.