Large animal models of heart failure

Congestive heart failure (HF) is a major focus of medical research. Its inc idence has greatly increased in recent decades because of art aging populat ion base and the increasingly successful treatment of other forms of chroni c cardiac disease. Relevant large animal models of HF should reflect the co mplex interactions of cardiac dysfunction, neurohumoral dynamics and periph eral vascular abnormalities found in human HF. A number of large animal mod els have been developed especially in dogs, sheep and swine, using naturall y occurring HE; or single or combinations of interventions, as instruments to trigger the development of HF. Naturally occurring HF models are not commonly used because of ethical or p erceived ethical grounds, however, King Charles Cavalier Spaniel and Yucata n Mini Pig models have been described. Tachycardia induced HF is the most c ommonly used HF model. Ventricular pacing at 220-240 bpm results in profoun d low output, biventricular, oedematous failure in two to three weeks. Lowe r pacing rates result in a more stable, sustainable, lesser degree of failu re. Positive features of this model include 'acceptance', aetiological rele vance to patient tachycardia induced HF, neurohumoral and functional profil e similar to most human HES relatively low cost simple preparation, ability to manipulate the degree of failure with pacing rate, reversibility, relia bility and a large amount of published multi species data. Limitations to t he use of the model are the rapid onset, the fact that reversibility is onl y relevant to the tachycardia induced patient HES the absence of hypertroph y in failure, the diminished plasma atrial natriuretic peptide (ANP) levels , absence of ANP of ventricular origin, and the interference between rapid pacing and therapeutic interventions. Myocardial damage models of HF includ e those models induced by ischaemia, eg due to coronary occlusion (ligation or aneroid) or intracoronary microembolism, transmyocardial DC shock, toxi c cardiomyopathy from adriamycin, doxorubicin or catecholamines. Overload m odels of HF may be induced by high pressure from aortic constriction, aorti c regurgitation, renal artery constriction, pulmonary stenosis or aortocava l shunts, or by induction of mitral regurgitation from chordae or leaflet d amage. No single, all-encompassing, large animal model of HF exists to dare. Selec tion of the type of model to be used should be based primarily on the hypot heses to be tested and secondarily on the available resources and facilitie s.