Research Article An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy Jesús Talavera, 1 Alejandro Giraldo, 2 María Josefa Fernández-Del-Palacio, 1 Obdulio García-Nicolás, 3,4 Juan Seva, 3 Gavin Brooks, 2 and Jose M. Moraleda 5 1 Departamento de Medicina y Cirug´ ıa Animal, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional “Campus Mare Nostrum”, 30100 Murcia, Spain 2 School of Biological Sciences, Institute for Cardiovascular and Metabolic Research, University of Reading, Reading RG6 6AS, UK 3 Departamento de Anatom´ ıa y Anatom´ ıa Comparada, Facultad de Veterinaria, Universidad de Murcia, Campus de Excelencia Internacional Regional “Campus Mare Nostrum”, 30100 Murcia, Spain 4 Institute of Virology and Immunology (IVI), Sensemattstrasse 293, 3147 Mittelh¨ ausern, Switzerland 5 Unidad de Trasplante Hematopoy´ etico y Terapia Celular, Departamento de Hematolog´ ıa, Hospital Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, 30120 Murcia, Spain Correspondence should be addressed to Jes´ us Talavera; talavera@um.es and Alejandro Giraldo; a.giraldoramirez@reading.ac.uk Received 21 August 2015; Revised 24 November 2015; Accepted 26 November 2015 Academic Editor: Peter M. Becher Copyright © 2015 Jes´ us Talavera et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 4mg/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. Tus, 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. 1. Introduction Anthracyclines (AC) such as doxorubicin and daunorubicin are regarded as one of the most efective chemotherapeutic groups ever developed for the treatment of malignancies, with a broad spectrum of action encompassing solid and haematologic tumours [1, 2]. Unfortunately, AC-induced cardiomyopathy (AICM) is a frequent toxic consequence of AC. It is estimated that in the USA alone there are at least 10 million cancer survivors, with a similar number in Europe [3, 4]. Tus, the recent success of chemotherapy in clinical oncology means that the population afected by AICM will likely increase substantially in the future. Several animal models and protocols for the induction of AICM in rodents (e.g., mice and rats) and lagomorphs (e.g., rabbits) have been published over the past decades. Of note, rabbit models of cardiac disease appear to have several advantages over animal models of other species. For example, Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 465342, 13 pages http://dx.doi.org/10.1155/2015/465342