Journal of Cardiac Failure
Volume 15, Issue 9 , Pages 798-804 , November 2009

Digitoxin Prolongs Survival of Female Rats With Heart Failure Due to Large Myocardial Infarction

  • Izo Helber, MD, PhD

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Alexandra A. Dos Santos, MD, PhD

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Ednei L. Antonio, MSc

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Ronald L.G. Flumignan, MD

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Danilo S. Bocalini, MSc

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Camila Piccolo

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • ,
  • Mihai Gheorghiade, MD, FACC

      Affiliations

    • Northwestern University, Chicago, IL
    • ,
  • Paulo J.F. Tucci, MD, PhD

      Affiliations

    • Cardiac Physiology and Physiopathology Laboratory, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    • Corresponding Author InformationReprint requests: Dr. Paulo JF Tucci, Rua Estado de Israel, 181/94, CEP: 04022-000, São Paulo, Brazil. Tel: (5511) 5572-1452.

Received 1 October 2008 ,Revised 23 April 2009 ,Accepted 4 May 2009.

References 

  1. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342:821–828
  2. Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, et al. A clinical trial of the angiotensin-converting-enzyne inhibitor tandolapril in patients with left ventricular dysfunction after myocardial infarction. Tandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med. 1995;333:1670–1676
  3. The Digitalis Investigation Group. The effects of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–533
  4. Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardium infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327:669–677
  5. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigators. N Engl J Med. 1992;327:685–691
  6. Adams KF, Patterson JH, Gattis WA, O'Connor CM, Lee CR, Schwartz TA, et al. Relationship of serum digoxin concentration to mortality and morbidity in women in the Digitalis Investigation Group Trial: a retrospective analysis. J Am Coll Cardiol. 2005;46:497–504
  7. Ahmed A. Digoxin and reduction in mortality and hospitalization in geriatric heart failure: importance of low doses and low serum concentrations. J Gerontol A Biol Sci Med Sci. 2007;62:323–329
  8. Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Aban IB, Colucci WS, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27:178–186
  9. Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation. 2006;113:2556–2564
  10. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289:871–878
  11. Rich MW, McSherry F, Williford WO, Yusuf S Digitalis Investigation Group. Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol. 2001;38:806–813
  12. Pfeffer MA, Pfeffer JM, Steinberg C, Finn P. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation. 1985;72:406–412
  13. Lapointe N, Blais C, Adam A, Parker T, Sirois MG, Gosselin H, et al. Comparison of the effects of an angiotensin-converting enzyme inhibitor and a vasopeptidase inhibitor after myocardial infarction in the rat. J Am Coll Cardiol. 2002;39:1692–1698
  14. Milavetz JJ, Raya TE, Johnson CS, Morkin E, Goldman S. Survival after myocardial infarction in rats: captopril versus losartan. J Am Coll Cardiol. 1996;27:714–719
  15. Marie C, Mossiat C, Gros C, Schwartz JC, Lecomte JM, Bralet J. Effect of long-term therapy with fasidotril, a mixed inhibitor of neprilysin and angiotensin-converting enzyme (ACE), on survival of rats after myocardial infarction. Cardiovasc Res. 1999;41:544–553
  16. Mulder P, Richard V, Derumeaux G, Hogie M, Henry JP, Lallemand F, et al. Role of endogenous endothelin in chronic heart failure: effect of long-term treatment with an endothelin antagonist on survival, hemodynamics, and cardiac remodeling. Circulation. 1997;96:1976–1982
  17. Sakai S, Miyauchi T, Kobayashi M, Yamaguchi I, Goto K, Sugishita Y. Inhibition of myocardial endothelin pathways improves long-term survival in heart failure. Nature. 1996;384:353–355
  18. Levijoki J, Pollesello P, Kaheinen P, Haikala H. Improved survival with simendan after experimental myocardial infarction in rats. Eur J Pharmacol. 2001;419:243–248
  19. Cury AF, Bonilha A, Saraiva R, Campos Fo O, Carvalho AC, de Paola AA, et al. Myocardial performance index in female rats with myocardial infarction: relationship with ventricular function parameters by Doppler echocardiography. J Am Soc Echocardiogr. 2005;18:454–460
  20. Kanashiro RM, Nozawa E, Murad N, Gerola LR, Moisés VA, Tucci PJF. Myocardial infarction scar plication in the rat: cardiac mechanics in an animal model for surgical procedures. Ann Thorac Surg. 2002;73:1507–1513
  21. Kanashiro RM, Saraiva RM, Alberta A, Antonio EL, Moisés VA, Tucci PJF. Immediate functional effects of left ventricular reduction: a Doppler echocardiographic study in the rat. J Card Fail. 2006;12:163–168
  22. Bonilha AM, Saraiva RM, Kanashiro RM, Portes LA, Antonio EL, Tucci PJF. A routine electrocardiogram cannot not be used to determine the size of myocardial infarction in the rat. Braz J Med Biol Res. 2005;38:615–619
  23. Helber I, Kanashiro RM, Alarcon EA, Antonio EL, Tucci PJF. A novel inexpensive murine model of oral chronic digitalization. Clin Exp Pharmacol Physiol. 2004;31:365–366
  24. Aldinger EE. Effects of digitoxin on the development of cardiac hypertrophy in the rat subjected to chronic exercise. Am J Cardiol. 1970;25:339–343
  25. Turto H, Lindy S. Digitoxin treatment and experimental cardiac hypertrophy in the rat. Cardiovasc Res. 1973;7:482–489
  26. Williams JF, Braunwald E Studies on digitalis. XI. Effects of digitoxin on the development of cardiac hypertrophy in the rat subjected to aortic constriction. Am J Cardiol. 1965;16:534–539
  27. Peron APON, Saraiva RM, Antonio EL, Andriolo A, Tucci PJF. Food restriction does not impair myocardial mechanics during the healing period of myocardial infarction in the rat. Nutr Res. 2005;25:1075–1084
  28. Flumignan RL, Kanashiro RM, Saraiva RM, Portes LA, Antonio EL, Ishigai MMS, et al. Incidence of heart failure in infarcted rats that die spontaneously. Braz J Med Biol Res. 2006;39:1323–1328
  29. Ahmed A, Waagstein F, Pitt B, White M, Zannad F, Young JB, et al. Effectivesess of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Am J Cardiol. 2009;103:82–87
  30. Oxman A, Guyatt GH. A consumer's guide to subgroup analyses. Ann Int Med. 1992;116:78–84
  31. Harrison LI, Gibaldi M. Pharmacokinetics of digoxin in the rat. Drug Metab Dispos. 1976;4:88–93
  32. Rietbrock N, Vöhringer HF. Metabolism and excretion of 3H-digitoxin in the rat. Biochem Pharmacol. 1974;23:2567–2575
  33. Ahmet I, Krawczyk M, Heller P, Moon C, Lakatta EG, Talan MI. Beneficial effects of chronic pharmacological manipulation of β-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy. Circulation. 2004;110:1083–1090
  34. dos Santos L, Mello AFS, Antonio EL, Tucci PJF. Determination of myocardial infarction size in rats by echocardiography and tetrazolium staining: correlation, agreements, and simplifications. Braz J Med Biol Res. 2008;41:199–201
  35. Allen JC, Schwartz A. A possible biochemical explanation for the insensitivity of the rat to cardiac glycosides. J Pharmacol Exp Ther. 1969;168:42–46
  36. Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB. Digitalis intoxication. A prospective clinical study with serum level correlations. N Engl J Med. 1971;284:989–997
  37. Adams KF, Gheorghiade M, Uretsky BF, Young JB, Ahmed S, Tomasko L, et al. Patients with mild heart failure worsen during withdrawal from digoxin therapy. J Am Coll Cardiol. 1997;30:42–48
  38. Packer M, Gheorghiade M, Young JB, Costantini PJ, Adams KF, Cody RJ, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med. 1993;329:1–7
  39. Uretsky B, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK. Ramdomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. J Am Coll Cardiol. 1993;22:955–962
  40. Arnold SB, Byrd RC, Meister W, Melmon K, Cheitlin MD, Bristow JD, et al. Long-term digitalis therapy improves left ventricular function in heart failure. N Engl J Med. 1980;303:1443–1448
  41. Wasserstrom JA, Aistrup GL. Digitalis: new actions for an old drug. Am J Physiol Heart Circ Physiol. 2005;289:H1781–H1793
  42. Gheorghiade M, Ferguson D. Digoxin: a neurohumoral modulator in heart failure?. Circulation. 1991;84:2181–2186

PII: S1071-9164(09)00142-0

doi: 10.1016/j.cardfail.2009.05.002

Journal of Cardiac Failure
Volume 15, Issue 9 , Pages 798-804 , November 2009

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