Bovine Model of Doxorubicin-Induced Cardiomyopathy英文文献资料.docVIP

HindawiPublishingCorporation JournalofBiomedicineandBiotechnology Volume2011,ArticleID758736,11pages doi:10.1155/2011/758736 ResearchArticle BovineModelofDoxorubicin-InducedCardiomyopathy GuruprasadA.Giridharan, CarloR.Bartoli,1,2,3KennethR.Brittian,3 4StevenC.Koenig, 2,4 andSumanthD.Prabhu3,5,6 TariqHamid, 3 1 2 3 4 5 6 MD/PhDProgram,DepartmentofPhysiologyandBiophysics,UniversityofLouisville,Louisville,KY40202,USA CardiovascularInnovationInstitute,UniversityofLouisville,Louisville,KY40202,USA DepartmentofMedicine,InstituteofMolecularCardiology,UniversityofLouisville,Louisville,KY40202,USA DepartmentofBioengineering,UniversityofLouisville,Louisville,KY40208,USA DepartmentofPhysiologyandBiophysics,UniversityofLouisville,Louisville,KY40202,USA RobleyRexVAMC,Louisville,KY40206,USA CorrespondenceshouldbeaddressedtoSumanthD.Prabhu,sprabhu@louisville.edu Received25August2010;Revised29October2010;Accepted16November2010 AcademicEditor:AndreaVecchione Copyright?2011CarloR.Bartolietal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Leftventricularassistdevices(LVADs)constitutearecentadvanceinheartfailure(HF)therapeutics.Astherigorousexperimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separateanimalswerestudiedascontrols.Doxorubicin-treatedanimalswerefollowedwithweeklyechocardiography.TargetLV dysfunctionwasde?nedasanejectionfraction ≤35%.Sixtydaysafterinitiatingdoxorubicin,aterminalstudywasperformed todeterminehemodynamic,histological,biochemical,andmolecularparameters.Allfourdoxorubicin-treatedanimalsexhibited signi?cant(P 0.05)contractiledysfunction,withtargetLVdysfunctionachievedinthreeanim