Introduction to Translational Research

  • J. Kevin Donahue
  • Maria Strom
  • Ian D. Greener


Translational research involves the process of validating ideas developed in nonclinical settings for use in patient care. It begins with the identification of a relevant and timely clinical problem (i.e., cardiac arrest, heart failure, atrial fibrillation), followed by investigation of the mechanisms responsible for disease pathogenesis, a step primarily performed at the scientific bench. Once the disease mechanisms are understood, potential therapy can then be rigorously tested in preclinical models (i.e., in silico, in vitro, in situ, in vivo). Efficacy and safety data in preclinical models can motivate early phase clinical testing. This chapter introduces the translational process and provides several examples.


Heart Failure Atrial Fibrillation Cardiac Arrest Chronic Heart Failure Mitral Regurgitation 
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  1. 1.
    Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119:e21–181.PubMedCrossRefGoogle Scholar
  2. 2.
    Haldeman GA, Croft JB, Giles WH, et al. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J 1999; 137:352–60.PubMedCrossRefGoogle Scholar
  3. 3.
    DiBianco R. Update on therapy for heart failure. Am J Med 2003; 115:480–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death. Circulation 1998; 98:946–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:2370–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics – 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008; 117:e25–146.PubMedCrossRefGoogle Scholar
  7. 7.
    Penado S, Cano M, Acha O, et al. Atrial fibrillation as a risk factor for stroke recurrence. Am J Med 2003; 114:206–10.PubMedCrossRefGoogle Scholar
  8. 8.
    Dulli DA, Stanko H, Levine RL. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 2003; 22:118–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Braunwald, E. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia: Elsevier Saunders, 1997.Google Scholar
  10. 10.
    Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling – concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 2000; 35:569–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Donahue JK, Heldman AW, Fraser H, et al. Focal modification of electrical conduction in the heart by viral gene transfer. Nat Med 2000; 6:1395–98.PubMedCrossRefGoogle Scholar
  12. 12.
    Sasano T, McDonald AD, Kikuchi K, et al. Molecular ablation of ventricular tachycardia after myocardial infarction. Nat Med 2006; 12:1256–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Smits AM, van Vliet P, Hassink RJ, et al. The role of stem cells in cardiac regeneration. J Cell Mol Med 2005; 9:25–36.PubMedCrossRefGoogle Scholar
  14. 14.
    Hajjar RJ, Zsebo K, Deckelbaum L, et al. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 2008; 14:355–67.PubMedCrossRefGoogle Scholar
  15. 15.
    Cox JL. The surgical treatment of atrial fibrillation. IV. Surgical technique. J Thorac Cardiovasc Surg 1991; 101:584–92.PubMedGoogle Scholar
  16. 16.
    O’Neill MD, Jais P, Hocini M, et al. Catheter ablation for atrial fibrillation. Circulation 2007; 116:1515–23.PubMedCrossRefGoogle Scholar
  17. 17.
    Billman GE. A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: implications for future anti-arrhythmic drug development. Pharmacol Ther 2006; 111:808–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Reimer KA, Jennings RB. The “wavefront phenomenon” of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow. Lab Invest 1979; 40:633–44.PubMedGoogle Scholar
  19. 19.
    Lowe JE, Reimer KA, Jennings RB. Experimental infarct size as a function of the amount of myocardium at risk. Am J Pathol 1978; 90:363–79.PubMedGoogle Scholar
  20. 20.
    Sabbah HN, Stein PD, Kono T, et al. A canine model of chronic heart failure produced by multiple sequential coronary microembolizations. Am J Physiol 1991; 260:H1379–84.PubMedGoogle Scholar
  21. 21.
    Whipple GH, Sheffield LT, Woodman EG, et al. Reversible congestive heart failure due to rapid stimulation of the normal heart. Proc New Engl Cardiovasc Soc 1962; 20:39–40.Google Scholar
  22. 22.
    Recchia FA, Lionetti V. Animal models of dilated cardiomyopathy for translational research. Vet Res Commun 2007; 31 Suppl 1:35–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Moe GW, Stopps TP, Angus C, et al. Alterations in serum sodium in relation to atrial natriuretic factor and other neuroendocrine variables in experimental pacing-induced heart failure. J Am Coll Cardiol 1989; 13:173–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Toyoda Y, Okada M, Kashem MA. A canine model of dilated cardiomyopathy induced by repetitive intracoronary doxorubicin administration. J Thorac Cardiovasc Surg 1998; 115:1367–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Allessie A, Bonke FI, Schopman FJG. Circus movement in rabbit atrial muscle as a mechanism of tachycardia: the role of nonuniform recovery of excitability in the occurrence of unidirectional block as studied with multiple microelectrodes. Circ Res 1977; 39:169–77.Google Scholar
  26. 26.
    Wijffels MCEF, Kirchhof CJHJ, Dorland R, et al. Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats – roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation. Circulation 1997; 96:3710–20.PubMedCrossRefGoogle Scholar
  27. 27.
    Ausma J, Wijffels M, Thoné F, et al. Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation 1997; 96:3157–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Li D, Melnyk P, Feng J, et al. Effects of experimental heart failure on atrial cellular and ionic electrophysiology. Circulation 2000; 101:2631–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Bauer A, McDonald AD, Donahue JK. Pathophysiological findings in a model of persistent atrial fibrillation and severe congestive heart failure. Cardiovasc Res 2004; 61:764–70.PubMedCrossRefGoogle Scholar
  30. 30.
    Smith RD. Avicenna and the Canon of Medicine: a millennial tribute. West J Med 1980; 133:367–70.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Heart and Vascular Research CenterCase Western Reserve University School of MedicineClevelandUSA

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