Veterinary Research Communications

, Volume 31, Supplement 1, pp 35–41 | Cite as

Animal Models of Dilated Cardiomyopathy for Translational Research

  • F. A. Recchia
  • V. Lionetti

Recchia, F.A. Lionetti, V., 2007. Animal models of dilated cardiomyopathy for translational research. Veterinary Research Communications, 31(Suppl. 1), 35–41


Animal models of cardiovascular disease have proved critically important for the discovery of pathophysiological mechanisms and for the advancement of diagnosis and therapy. They offer a number of advantages, principally the availability of adequate healthy controls and the absence of confounding factors such as marked differences in age, concomitant pathologies and pharmacological treatments. Dilated cardiomyopathy (DCM) is the third cause of heart failure (HF) and is characterized by progressive ventricular dilation and functional impairment in the absence of coronary lesions and/or hypertension. Over the past thirty years, investigators have developed numerous small and large animal models to study this very complex syndrome. Genetically modified mice are the most widely and intensively utilized research animals and allow high throughput studies on DCM. However, to translate discoveries from basic science into medical applications, research in large animal models becomes a necessary step. An accurate large animal model of DCM is pacing-induced HF. It is obtained by continuous cardiac pacing at a frequency three- to fourfold higher than the spontaneous heart rate and is mostly applied to dogs, but also to pigs, sheep and monkeys. To date, this model can still be considered a gold standard in HF research.


dilated cardiomyopathy experimental animal models heart failure 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anzai T., Lai N.C., Gao M. and Hammond H.K., 1998. Dissociation between regional dysfunction and beta-adrenergic receptor signaling in heart failure. The American Journal of Physiology Heart Circulation Physiology, 275, H1267–H1273Google Scholar
  2. Armstrong P.W., Stopps T.P., Ford S.E. and De Bold A.J., 1986. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circulation, 74, 1075–1084PubMedGoogle Scholar
  3. Benjamin I.J. and Schneider M.D., 2005. Learning from failure: congestive heart failure in the postgenomic age. The Journal of Clinical Investigation, 115, 495–499PubMedCrossRefGoogle Scholar
  4. Bleumink G.S., Knetsch A.M., Sturkenboom M.C., Straus S.M., Hofman A., Deckers J.W., Witteman J.C. and Stricker B.H., 2004. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. European Heart Journal, 25, 1614–1619PubMedCrossRefGoogle Scholar
  5. Bolli R., Becker L., Gross G., Mentzer R., Balshaw D. and Lathrop D.A., 2004. Myocardial protection at a crossroads. The need for translation into clinical therapy. Circulation Research, 95, 125–134PubMedCrossRefGoogle Scholar
  6. Felker G.M., Thompson R.E., Hare J.M., Hruban R.H., Clemetson D.E., Howard D.L., Baughman K.L. and Kasper E.K., 2000. Underlying causes and longterm survival in patients with initially unexplained cardiomyopathy. The New England Journal of Medicine, 342, 1077–1084PubMedCrossRefGoogle Scholar
  7. Goineau S., Pape D., Guillo P., Ramee M.P. and Bellissant E., 2001. Increased sensitivity of vascular smooth muscle to nitric oxide in dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain). Journal of Cardiovascular Pharmacology, 37, 290–300PubMedCrossRefGoogle Scholar
  8. Grunig E., Tasman J.A., Kucherer H., Franz W., Kubler W. and Katus H.A., 1998. Frequency and phenotypes of familial dilated cardiomyopathy. Journal of the American College of Cardiology, 31, 186–194PubMedCrossRefGoogle Scholar
  9. Grzeskowiak R., Witt H., Drungowski M., Thermann R., Hennig S., Perrot A., Osterziel K.J., Klingbiel D., Scheid S., Spang R., Lehrach H. and Ruiz P., 2003. Expression profiling of human idiopathic dilated cardiomyopathy. Cardiovascular Research, 59, 400–411PubMedCrossRefGoogle Scholar
  10. Hearse D.J. and Yellon D.M., 1984. Therapeutic approaches to myocardial infarct size limitation, (Raven Press, New York)Google Scholar
  11. Hearse D.J. and Sutherland F.J., 2000. Experimental models for the study of cardiovascular function and disease. Pharmacological Research, 41, 597–603PubMedCrossRefGoogle Scholar
  12. Howard R.J., Moe G.W. and Armstrong P.W., 1991. Sequential echocardiographic-Doppler assessment of left ventricular remodelling and mitral regurgitation during evolving experimental heart failure. Cardiovascular Research, 25, 468–474PubMedGoogle Scholar
  13. Ikeda Y. and Ross J. Jr., 2000. Models of dilated cardiomyopathy in the mouse and the hamster. Current Opinion in Cardiology, 15, 197–201PubMedCrossRefGoogle Scholar
  14. Jessup M. and Brozena S., 2003. Heart failure. The New England Journal of Medicine, 348, 2007–2018PubMedCrossRefGoogle Scholar
  15. Lei B., Lionetti V., Young M.E., Chandler M.P., d’Agostino C., Kang E., Altarejos M., Matsuo K., Hintze T.H., Stanley W.C. and Recchia F.A., 2004. Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. Journal of Molecular and Cellular Cardiology, 36, 567–576PubMedCrossRefGoogle Scholar
  16. Lionetti V., Linke A., Chandler M.P., Young M.E., Penn M.S., Gupte S., d’Agostino C., Hintze T.H., Stanley W.C. and Recchia F.A., 2005. Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure. Cardiovascular Research, 66, 454–461PubMedCrossRefGoogle Scholar
  17. Moe G.W., Angus C., Howard R.J., Parker T.G. and Armstrong P.W., 1992. Evaluation of indices of left ventricular contractility and relaxation in evolving canine experimental heart failure. Cardiovascular Research, 26, 362–366PubMedCrossRefGoogle Scholar
  18. Mollnau H., Oelze M., August M., Wendt M., Daiber A., Schulz E., Baldus S., Kleschyov A.L., Materne A., Wenzel P., Hink U., Nickenig G., Fleming I. and Münzel T., 2005. Mechanisms of increased vascular superoxide production in an experimental model of idiopathic dilated cardiomyopathy. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 2554–2559PubMedCrossRefGoogle Scholar
  19. Morgan D.E., Tomlinson C.W., Qayumi A.K., Toleikis P.M., McConville B. and Jamieson W.R., 1989. Evaluation of ventricular contractility indexes in the dog with left ventricular dysfunction induced by rapid atrial pacing. Journal of the American College of Cardiology, 14, 489–495PubMedCrossRefGoogle Scholar
  20. Mulder P., Richard V., Compagnon P., Henry J.P., Lallemand F., Clozel J.P., Koen R., Mace B. and Thuillez C., 1997. Increased survival after long-term treatment with mibefradil, a selective T-channel calcium antagonist, in heart failure. Journal of the American College of Cardiology, 29, 416–421PubMedCrossRefGoogle Scholar
  21. Olson T.M., Michels V.V., Thibodeau S.N., Tai Y.S. and Keating M.T., 1998. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science, 280, 750–752PubMedCrossRefGoogle Scholar
  22. Recchia F.A., McConnell P.I., Bernstein R.D., Vogel T.R., Xu X.B. and Hintze T.H., 1998. Reduced nitric oxide production and altered myocardial metabolism during decompensation of pacing- induced heart failure in the conscious dog. Circulation Research, 83, 969–979PubMedGoogle Scholar
  23. Ryoke T., Gu Y., Mao L., Hongo M., Clark R.G., Peterson K.L. and Ross J. Jr., 1999. Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition. Circulation, 100, 1734–1743PubMedGoogle Scholar
  24. Spinale F.G., Hendrick D.A., Crawford F.A., Smith A.C., Hamada Y. and Carabello B.A., 1990. Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine. The American Journal of Physiology, 259, H218–H229PubMedGoogle Scholar
  25. Towbin J.A., Lowe A.M., Colan S.D., Sleeper L.A., Orav E.J., Clunie S., Messere J., Cox G.F., Lurie P.R., Hsu D., Canter C., Wilkinson J.D. and Lipshultz S.E., 2006. Incidence, causes, and outcomes of dilated cardiomyopathy in children. Journal of the American Medical Association, 296, 1867–1876PubMedCrossRefGoogle Scholar
  26. Trochu J.N., Mital S., Zhang X., Xu X., Ochoa M., Liao J.K., Recchia F.A. and Hintze T.H., 2003. Preservation of NO production by statins in the treatment of heart failure. Cardiovascular Research, 60, 250–258PubMedCrossRefGoogle Scholar
  27. Villard E., Duboscq-Bido L., Charron P., Benaiche A., Conraads V., Sylvius N. and Komajda M., 2005. Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene. European Heart Journal, 26, 794–803PubMedCrossRefGoogle Scholar
  28. Whipple G.H., Sheffield L.T., Woodman E.G., Theophilis C. and Friedman S., 1962. Reversible congestive heart failure due to chronic rapid stimulation of the normal heart. Proceedings of New England Cardiovascular Society, 20, 39–40Google Scholar
  29. Yarbrough W.M. and Spinale F.G., 2003. Large animal models of congestive heart failure: a critical step in translating basic observations into clinical applications. Journal of Nuclear Cardiology, 10, 77–86PubMedCrossRefGoogle Scholar
  30. Yoo K.J., Li R.K., Weisel R.D., Mickle D.A., Jia Z.Q., Kim E.J., Tomita S. and Yau T.M., 2000. Heart cell transplantation improves heart function in dilated cardiomyopathic hamsters. Circulation, 102, 204–209Google Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  1. 1.Scuola Superiore Sant’Anna, Sector of MedicinePisaItaly
  2. 2.Institute of Clinical Physiology, CNRPisaItaly
  3. 3.Department of PhysiologyNew York Medical CollegeValhallaUSA

Personalised recommendations