title: An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy.
abstract: Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.
authors.affiliation: Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional "Campus Mare Nostrum", 30100 Murcia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Talavera
authors.affiliation: School of Biological Sciences, Institute for Cardiovascular and Metabolic Research, University of Reading, Reading RG6 6AS, UK.
authors.forename: Alejandro
authors.identifier: 0000-0001-8594-338X
authors.initials: A
authors.lastname: Giraldo
authors.affiliation: Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional "Campus Mare Nostrum", 30100 Murcia, Spain.
authors.forename: María Josefa
authors.initials: MJ
authors.lastname: Fernández-Del-Palacio
authors.affiliation: Departamento de Anatomía y Anatomía Comparada, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional "Campus Mare Nostrum", 30100 Murcia, Spain; Institute of Virology and Immunology (IVI), Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland.
authors.forename: Obdulio
authors.initials: O
authors.lastname: García-Nicolás
authors.affiliation: Departamento de Anatomía y Anatomía Comparada, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional "Campus Mare Nostrum", 30100 Murcia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Seva
authors.affiliation: School of Biological Sciences, Institute for Cardiovascular and Metabolic Research, University of Reading, Reading RG6 6AS, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Brooks
authors.affiliation: Unidad de Trasplante Hematopoyético y Terapia Celular, Departamento de Hematología, Hospital Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, 30120 Murcia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moraleda
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000633:toxicity; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D003630:Daunorubicin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D004452:Echocardiography; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000473:pathology; D011817:Rabbits
chemical_list: D018943:Anthracyclines; D004317:Doxorubicin; D003630:Daunorubicin