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Stellenwert von Digitalis in der Therapie der akuten und chronischen Herzinsuffizienz

Digitalis in the management of acute and chronic heart failure

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Zusammenfassung

□ Der Stellenwert von Digitalis in der Therapie der Herzinsuffizienz ist bis zum heutigen Tag nicht zweifelsfrei geklärt. Die Mehrzahl der seit 1980 publizierten klinischen Studien läßt erkennen, daß Digitalis, vor allem bei fortgeschrittenen Stadien der chronischen Herzinsuffizienz, eine Verbesserung der klinischen Symptome bewirken kann. Der Wirkungsmechanismus von Digitalis am insuffizienten Myokard hat in den letzten Jahren durch zahlreiche grundlagen-wissenschaftliche Arbeiten weitere Komplexität erlangt. Umfangreiche randomisierte klinische Studien an großen Patientenkollektiven zur Wirksamkeit von Digitalis bei Patienten mit Herzinsuffizienz und Sinusrhythmus sind erst in den letzten Jahren publiziert worden. Diese Studien lassen erkennen, daß Digitalis eine symptomatische Verbesserung bei diesen Patienten bewirken kann. Im Gegensatz zur mortalitätsbeeinflussenden Wirkung von ACE-Hemmern hat aber Digitalis keinen Effekt auf die Langzeitmortalität bei der chronischen Herzinsuffizienz. Anhand der vorliegenden Daten ist Digitalis ein Zusatzmedikament in der symptomatischen Therapie der chronischen Herzinsuffizienz.

Summary

□ Although supported by more than 200 years of experience and anecdotal clinical evidence, the efficiacy of digitalis in the management of heart failure has been questioned until the past decade. The idea to improve contractility of the diseased myocardium with an inotropic agent is fundamental in the management of left ventricular dysfunction. The majority of clinical trials published since 1980, most of which examined patients with mild to moderate heart failure, indicate that digitalis alone or in combination with vasodilators may improve the clinical outcome particular in those patients with more advanced symptoms and poorer left ventricular function. Aside from its action as an inotropic drug the pharmacology and the mechanisms by which digitalis influence the diseased myocardium and peripheral circulation in heart failure has gained more complexity within the last years, raising the idea of other mechanisms that might be involved in its action. Particular for ACE inhibition multiple clinical trials have conclusively demonstrated its impact on survival and morbidity in congestive heart failure. Improvement of clinical outcome as measured in terms of fewer hospitalizations and improvement of symptoms in patients receiving digitalis seems to be comparable to patients receiving β-blockers additional to diuretics and ACE inhibitors, an entirely different approach to the treatment of heart failure. Despite initial improvement of hemodynamics it now appears that there is no survival benefit found for digitalis in the management of heart failure.

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Literatur

  1. Andresen, D., G. Steinbeck, T. Brüggemann, R. Haberl, D. Müller, R. Dissmann, G. Langenscheidt, H. P. Schultheiß: Digitalis-Therapie: unabhängiger Risikofaktor bei Postinfarkt-Patienten. Z. Kardiol. 85, Suppl. 2 (1996), 250.

    Google Scholar 

  2. Beaune, J.: Comparison of enalapril versus digoxin for congestive heart failure. Amer. J. Cardiol. 63 (1989), D22-D25.

    Article  Google Scholar 

  3. Beukelmann, D. J., E. Erdmann: Digitalistherapie 1994. Internist (Berl.) 35 (1994), 872–876.

    Google Scholar 

  4. Beukelmann, D. J., M. Nähbauer, E. Erdmann: Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 85 (1992), 1046–1055.

    Google Scholar 

  5. Beukelmann, D. J., W. G. Weir: Mechanisms of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J. Physiol. 405 (1988), 233–255.

    Google Scholar 

  6. Blaustein, M. P.: The cellular basis of cardiotonic steroid action. TIPS 6 (1985), 289–292.

    CAS  Google Scholar 

  7. Boehm, M., K. la Rosee, U. Schmidt, C. Schulz, R. H. G. Schwinger, E. Erdmann: Force-frequency relationship and inotropic stimulation in the non-failing and failing human myocardium: implications for the medical treatment of heart failure. Clin. Invest. 70 (1992), 421–424.

    Article  Google Scholar 

  8. Braunwald, E.: Effects of digitalis on the normal and the failing heart. J. Amer. Coll. Cardiol. 5, Suppl. A (1985), 51A-59A.

    CAS  Google Scholar 

  9. Bridge, J. H. B., J. Smolley, K. W. Spitzer: The relationship between charge movements associated with ICa and INa-Ca in cardiac myocytes. Science 248 (1990), 376–378.

    Article  PubMed  CAS  Google Scholar 

  10. Cannell, M. B., J. R. Berlin, W. J. Lederer: Effects of membrane potential changes on the calcium transient in single rat cardiac muscle cells. Science 238 (1987), 1419–1423.

    Article  PubMed  CAS  Google Scholar 

  11. Captopril-Digoxin-Multicenter Research Group: Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. J. Amer. med. Ass. 259 (1988), 539–544.

    Article  Google Scholar 

  12. Carmeliet, E.: A fuzzy subsarcolemmal space for intracellular Na+ in cardiac cells. Cardiovasc. Res. 26 (1992), 433–442.

    Article  PubMed  CAS  Google Scholar 

  13. Charlemagne, D.: Molecular and cellular level of action of digitalis. Herz 18 (1993), 79–85.

    PubMed  CAS  Google Scholar 

  14. Cohen, C. J., H. A. Fozzard, S. S. Sheu: Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle. Circulat. Res. 50 (1982), 651–662.

    PubMed  CAS  Google Scholar 

  15. Davies, R. F., B. S. Beanlands, Nadeau: Enalapril versus digoxin in patients with congestive heart failure: a multicenter study. J. Amer. Coll. Cardiol. 18 (1991), 1602–1609.

    CAS  Google Scholar 

  16. Di Bianco, R., R. Shabetai, W. Kostuk, J. Moran, R. C. Schlauf, R. Wright: A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. New Engl. J. Med. 320 (1989), 677–683.

    Google Scholar 

  17. Dobbs, S. N., W. I. Kenyon, R. J. Dobbs: Maintenance digoxin after an episode of heart failure: placebo controlled trial in outpatients. Brit med. J. 1 (1977), 749–752.

    Article  PubMed  CAS  Google Scholar 

  18. Eisner, D. A., T. W. Smith: The Na−K pump and its effectors in cardiac muscle. In: Fozzard, H. A., E. Haber, R. B. Jennings, A. M. Katz (eds.) The Heart and Cardiovascular System. Raven Press, New York 1992, p. 863–902.

    Google Scholar 

  19. Ellis, D.: The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J. Physiol. 273 (1977), 211–240.

    PubMed  CAS  Google Scholar 

  20. Fabiato, A.: Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Amer. J. Physiol. 245 (1983), C1-C14.

    PubMed  CAS  Google Scholar 

  21. Fabiato, A.: Stimulated calcium current can both cause calcium loading in, and trigger calcium release from, the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J. gen. Physiol. 85 (1985), 247–289.

    Article  PubMed  CAS  Google Scholar 

  22. Feldman, M. D., J. D. Alderman, J. M. Aroesty, H. D. Royal, J. J. Ferguson, R. M. Owen, W. Grossman, R. G. McKay: Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy. J. clin. Invest. 82 (1988), 1661–1669.

    Article  PubMed  CAS  Google Scholar 

  23. Ferguson, D. W., F. M. Abboud, A. L. Mark: Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction. Circulation 69 (1984), 451–460.

    PubMed  CAS  Google Scholar 

  24. Ferguson, D. W., W. J. Berg, J. S. Saunders: Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathic neural recordings. Circulation 80 (1989), 65–77.

    PubMed  CAS  Google Scholar 

  25. Fleg, L., S. H. Gottlieb, E. G. Lakatta: Is digoxin really important in compensated heart failure? Amer. J. Med. 73 (1982), 244–250.

    Article  PubMed  CAS  Google Scholar 

  26. Frampton, J. E., C. H. Orchard, M. R. Boyett: Diastolic, systolic, and sarcoplasmic reticulum (Ca2+) during inotropic interventions in isolated rat cardiac myocytes. J. Physiol. 437 (1991), 351–375.

    PubMed  CAS  Google Scholar 

  27. Frank, J. S., G. Mottino, D. Reid, R. S. Molday, K. D. Philipson: Distribution of the Na/Ca exchange protein in mammalian cardiac myocytes: an immunofluoresence and immunocolloidal gold labeling study. J. Cell Biol. 117 (1992), 337–345.

    Article  PubMed  CAS  Google Scholar 

  28. Gadsby, D. C.: The Na/K pump of cardiac cells. Ann. Rev. Biophys. Bioengng. 13 (1984), 373–398.

    Article  CAS  Google Scholar 

  29. German and Austrian-Xamoterol-Study Group: Double-blind placebo controlled comparison of digoxin and xamoterol in chronic heart failure. Lancet (1988), i489–i493.

  30. Gheorghiade, M., J. StClair, C. StClair, G. A. Beller: Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators. J. Amer. Coll. Cardiol. 9 (1987), 849–857.

    CAS  Google Scholar 

  31. Gheorghiade, M., V. Hall, J. Lakie, S. Goldstein: Comparative hemodynamic and neurohumoral effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. J. Amer. Coll. Cardiol. 13 (1989), 134–142.

    Article  CAS  Google Scholar 

  32. Guyatt, G. H., M. J. J. Sullivan, E. L. Fallen: A controlled trial of digoxin in congestive heart failure. Amer. J. Cardiol. 61 (1988), 371–375.

    Article  PubMed  CAS  Google Scholar 

  33. Haerer, W., U. Bauer, M. Hetzel, J. Fehske: Long-term effects of digoxin and diuretics in congestive heart failure: results of a placebo-controlled randomized double-blind study. Circulation 78, Suppl. II (1988), II-53.

    Google Scholar 

  34. Harrison, S. M., E. McCal, M. R. Boyett: The relationship between contraction and intracellular sodium in rat and guinea-pig ventricular myocytes. J. Physiol. 449 (1992), 517–550.

    PubMed  CAS  Google Scholar 

  35. Hassenfuss, G., H. Reinecke, R. Studer, M. Meyer, B. Pieske, J. Holtz, C. Holubarsch, H. Posival, H. Just, H. Drexler: Relation between myocardial function and expression of sarcoplasmic reticulum Ca2+-ATPase in failing and nonfailing human myocardium. Circulat. Res. 75 (1994), 434–442.

    Google Scholar 

  36. Heck, I., H. M. Müller, H. Esser, B. Lüderitz: Captopril versus Digoxin in der Behandlung der leichten bis mittelschweren Herzinsuffizienz. Dtsch. med. Wschr. 114 (1989), 695–699.

    PubMed  CAS  Google Scholar 

  37. Herlitz, J.: Comparison of lisinopril versus digoxin for congestive heart failure during maintenance diuretic therapy. Amer. J. Cardiol. 70 (1992), C84-C90.

    Article  Google Scholar 

  38. Higgins, C. B., S. F. Vatner, E. Braunwald: Regional and hemodynamic effects of a digitalis glycoside in the conscious dog with and without experimental heart failure. Circulat. Res. 30 (1972), 406–417.

    PubMed  CAS  Google Scholar 

  39. Im, W. B., C. O. Lee: Quantitative relation of twitch and tonic tensions to intracellular Na+ activity in cardiac Purkinje fibres. Amer. J. Physiol. 247 (1984), C478-C487.

    PubMed  CAS  Google Scholar 

  40. Johnson, E. A., R. D. Lemieux. Sodium-calcium exchange. Science 251 (1991), 1370.

    Article  CAS  Google Scholar 

  41. Just, H., H. Drexler, S. H. Taylor, J. Siegrist, G. Schulgen, M. Schumacher: Captopril versus digoxin in patients with coronary artery disease and mild heart failure. A prospective, double-blind, placebo-controlled multicenter study. The CADS study group. Herz 18, Suppl. 1 (1993), 436–443.

    PubMed  Google Scholar 

  42. Kelly, R. A., T. W. Smith: Digoxin in heart failure: implications of recent trials. J. Amer. Coll. Cardiol. 22, Suppl. A (1993), 107A-112A.

    Article  CAS  Google Scholar 

  43. Kinugawa, T., M. E. Dibner-Dunlap: Altered vagal and sympathethic control of heart rate in left ventricular dysfunction and heart failure. Amer. J. Physiol. 268 (1995), R317-R323.

    PubMed  CAS  Google Scholar 

  44. Kober, L., C. Torp-Pedersen, N. Gadsboll, P. Hildebrandt, P. F. Hoilund-Carlson: Is digoxin an independent risk factor for long-term mortality after acute myocardial infarction? Europ. Heart J. 15 (1994), 382–388.

    CAS  Google Scholar 

  45. Kohimoto, O., A. J. Levi, J. H. B. Bridge: Relation between reverse Na−Ca exchange and sarcoplasmic reticulum Ca release in guinea pig ventricular cells. Circulat. Res. 74 (1994), 550–554.

    Google Scholar 

  46. Kranzhöfer, R., M. Haass, T. Kurz, G. Richard, A. Schömig: Effects of digitalis glycosides on norepinephrine release in the heart. Dual mechanism of action. Circulat. Res. 68 (1991), 1628–1637.

    PubMed  Google Scholar 

  47. Kromer, E., D. Elsner, G. A. J. Riegger: Digoxin, converting enzyme inhibition (quinalapril), and the combination in patients with congestive heart failure functional class II and sinus rhythm. J. cardiovasc. Pharmacol. 16 (1990), 9–14.

    Article  PubMed  CAS  Google Scholar 

  48. Krum, H., J. T. Bigger, R. L. Goldsmith, M. Packer: Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure. J. Amer. Coll. Cardiol. 25 (1995), 289–294.

    Article  CAS  Google Scholar 

  49. Lagerlof, H., L. Werko: Studies on the circulation in man: the effect of cedilanid (lanatoside C) on cardiac output and blood pressure in the pulmonary circulation in patients with compensated and decompensated heart disease. Acta cardiol. (Brux.) 4 (1944), 1.

    Google Scholar 

  50. Lamb, J. F.: Regulation of the abundance of sodium pumps in isolated animal cells. Int. J. Biochem. 22 (1990), 1365–1370.

    Article  PubMed  CAS  Google Scholar 

  51. Lang, R., H. O. Klein, E. Weiss, D. David, P. Saroli: Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation. Chest 83 (1983), 491–499.

    Article  PubMed  CAS  Google Scholar 

  52. Lang, S., M. P. Blaustein: The role of the sodium pump in the control of vascular tone in the rat. Circulat. Res. 46 (1980), 463–470.

    PubMed  CAS  Google Scholar 

  53. LeBlanc, N., J. R. Hume: Sodium current-induced release of calcium of cardiac sarcoplamic reticulum. Science 248 (1990), 372–376.

    Article  PubMed  CAS  Google Scholar 

  54. Lederer, W. J., E. Niggli, R. W. Hardley: Sodium-calcium exchange in excitable cells: fuzzy space. Science 248 (1990), 283.

    Article  PubMed  CAS  Google Scholar 

  55. Lee, C. O., A. J. Levi: The role of intracellular sodium in the control of cardiac contraction. Ann. N. Y. Acad. Sci. 639 (1991), 408–428.

    Article  PubMed  CAS  Google Scholar 

  56. Lee, C. O.: 200 years of digitalis: the emerging central role of the sodium ion in the control of cardiac force. Amer. J. Physiol. 249 (1985), C367–378.

    PubMed  CAS  Google Scholar 

  57. Lee, D. C. S., R. A. Johnson, J. B. Bingham, M. Leahy, R. E. Dinsmore, A. H. Geroll, J. B. Newel, J. B. Strauss, E. Haber: Heart failure in outpatients: a randomized trial of digoxin versus placebo. New Engl. J. Med. 306 (1982), 699–705.

    Article  PubMed  CAS  Google Scholar 

  58. Lee, K. S., W. Klaus: The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol. Rev. 23 (1971), 193–261.

    PubMed  CAS  Google Scholar 

  59. Leor, J., U. Goldbourt, S. Behar, V. Boyko, H. Reicher-Reiss, E. Kaplinsky, B. Rabinowitz: Digoxin and mortality in survivors of acute myocardial infarction: observation in patients at low and intermediate risk. The SPINT study group. Cardiovasc. Drugs Ther. 9 (1995), 609–617.

    Article  PubMed  CAS  Google Scholar 

  60. Levi, A. J.: The electrogenic sodium-potassium pump and passive sodium influx of isolated guinea-pig ventricular myocytes. J. cardiovasc. Electrophys. 3 (1992), 225–238.

    Article  Google Scholar 

  61. Levi, A. J., M. R. Boyett: The relation between contraction and intracellular sodium during inotropy in voltage-clamped sheep Purkinje fibres. J. cardiovasc. Electrophys. 2 (1991), 134–144.

    Article  Google Scholar 

  62. Levi, A. J., P. Brooksby, J. Hancox: One hump or two? The triggering of calcium release from the sarcoplasmic reticulum and the voltage dependence of contraction in mammalian cardiac muscle. Cardiovasc. Res. 27 (1993), 1743–1757

    Article  PubMed  CAS  Google Scholar 

  63. Lingrel, J. B., T. Kuntzweiler: Na+, K+-ATPase. J. biol. Chem. 269 (1994), 19659–19662.

    PubMed  CAS  Google Scholar 

  64. Mark, A. L.: Sympathic dysregulation in heart failure: mechanisms and therapy. Clin. Cardiol. 18, Suppl. 1 (1995), 13–18.

    Google Scholar 

  65. Mason, D. T., E. Braunwald, R. B. Karash, F. A. Bullock: Studies on digitalis X: effects of ouabain on forearm vascular resistance and venous tone in normal subjects and in patients with heart failure. J. clin. Invest. 43 (1964), 532.

    Article  PubMed  CAS  Google Scholar 

  66. McDonough, A. A., J. Wang, R. A. Farley: Significance of sodium pump isoforms in digitalis therapy. J. molec. cell. Cardiol. 27 (1995), 1001–1009.

    Article  CAS  Google Scholar 

  67. McGarry, S. J., A. J. Williams: Digoxin activates sarcoplasmic reticulum Ca2+-release channels: a posible role in cardiac inotropy. Brit. J. Pharmacol. 108 (1993), 1043–1050.

    CAS  Google Scholar 

  68. McGarry, S. J., A. J. Williams: Therapeutic concentrations of digoxin activate the cardiac but not the skeletal, sarcoplasmic reticulum Ca2+ release channel. J. molec. cell. Cardiol. 24, Suppl. IV (1992), IV-46.

    Google Scholar 

  69. McLain, P. L.: Effects of cardiac glycosides on spontaneous efferent activity in vagus and sympathic nerves of cats. Int. J. Neuropharmacol. 8 (1969), 379–387.

    Article  PubMed  CAS  Google Scholar 

  70. McLain, P. L.: Effects of ouabain on spontaneous afferent activity in the aortic and carotid sinus nerves of cats. Neuropharmacology 9 (1970), 399–402.

    Article  PubMed  CAS  Google Scholar 

  71. McMichael, J.: Digitalis in the last half century. Europ. Heart J. 3, Suppl. D (1982), D3–4.

    Google Scholar 

  72. Mogul, D. J., D. H. Singer, R. E. Ten Eick: Dependence of Na−K-pump current on internal Na+ in mammilian cardiac myocytes. Amer. J. Physiol. (1990), H488–H496.

  73. Molstad, P., M. Abdelnoor: Digitoxin-associated mortality in acute myocardial infarction. Europ. Heart J. 12 (1991), 65–69.

    CAS  Google Scholar 

  74. Morgan, J. P.: Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. New Engl. J. Med. 325 (1991), 625–632.

    Article  PubMed  CAS  Google Scholar 

  75. Mulieri, L. A., G. Hasenfuss, B. Leavitt, P. D. Allen, N. R. Alpert: Altered myocardial force-frequency relation in human heart failure. Circulation 85 (1992), 1743–1750.

    PubMed  CAS  Google Scholar 

  76. Nicoll, D. A., S. Longoni, K. D. Philipson: Molecular cloning and functional expression of the cardiac sarcolemmal Na−Ca exchanger. Science 250 (1990), 562–565.

    Article  PubMed  CAS  Google Scholar 

  77. Nolte, C. W., S. Jost, A. Mugge, W. G. Daniel: Digoxin-induced constriction of epicardial coronary vessels in patients with coronary artery disease: reversibility by nitrates. Z. Kardiol. 83 (1994), 711–716.

    PubMed  CAS  Google Scholar 

  78. Osterziel, K. J., R. Dietz, J. Manthey, W. Schmid, W. Kübler: Hemodynamic changes caused by alterations of autonomic activity in patients with heart failure. Brit. Heart J. 63 (1990), 221–224.

    Article  PubMed  CAS  Google Scholar 

  79. Packer, M., M. Gheorghiade, J. B. Young, P. J. Constantini, K. F. Adams, R. J. Cody, L. K. Smith, L. van Voorhees, L. A. Gourley, M. K. Jolly: Withdrawal of digoxin from patients treated with angiotensin converting enzyme inhibitors. New Engl. J. Med. 329 (1993), 1–7.

    Article  PubMed  CAS  Google Scholar 

  80. Peters, T., R. H. Raben, O. Wassermann: Evidence for a dissociation between positive inotropic effect and inhibition of Na+−K+-ATPase by ouabain, cassain, and their alkylating derivates. Europ. J. Pharmacol. 26 (1974), 166–174.

    Article  CAS  Google Scholar 

  81. Raabe, D. S.: Combined therapy with digoxin and nitroprusside in heart failure complicating acute myocardial infarction. Amer. J. Cardiol. 43 (1979), 990–994.

    Article  PubMed  Google Scholar 

  82. Rea, R. F., W. J. Berg: Abnormal baroreflex mechanisms in congestive heart failure. Editorial. Circulation 81 (1990), 2026–2027.

    PubMed  CAS  Google Scholar 

  83. Repke, K. R., R. Megges, J. Weiland, R. Schon: Location and properties of the digitalis receptor site in Na+/K(+)-ATPase. Fed. Europ. biochem. Soc. Lett. 359 (1995), 107–109.

    CAS  Google Scholar 

  84. Ribner, B., D. A. Plucinski, A. M. Hsieh, D. Bresnahan, A. Molteni, J. Askenazi, M. Lesch: Acute effects of digoxin on total systemic vascular resistance in congestive heart failure due to dilated cardiomyopathy: a hemodynamic-hormonal study. Amer. J. Cardiol. 56 (1985), 896–904.

    Article  PubMed  CAS  Google Scholar 

  85. Ribner, H. S., M. J. Zucker, C. Staisor: Vasodilators as a first-line therapy for congestive heart failure: a comparative hemodynamic study of hydralazine, digoxin and their combination. Amer. Heart J. 114 (1987), 91.

    Article  PubMed  CAS  Google Scholar 

  86. Ross, J. J., J. A. Waldhausen, E. Braunwald: Studies on digitalis: direct effects on peripheral vascular resistance. J. clin. Invest. 39 (1960), 930.

    Article  PubMed  CAS  Google Scholar 

  87. Schmidt, H., R. H. G. Schwinger, M. Boehm, E. Erdmann: Alterations of the force-frequency relation depending on stages of heart failure in humans. Amer. J. Cardiol. 74 (1994), 1066–1068.

    Article  PubMed  CAS  Google Scholar 

  88. Schwinger R. H. G., M. Böhm, J. Müller-Ehmsen, R. Uhlmann, U. Schmidt, A. Stäblein, P. Überfuhr, E. Kreuzer, B. Reichart, H. J. Eissner, E. Erdmann: Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart. Circulation 88 (1993), 2267–2276.

    PubMed  CAS  Google Scholar 

  89. Sham, J. S. K., L. Cleemann, M. Morad: Gating of the Ca2+ release channel: The role of Na+ current and Na+−Ca2+ exchange. Science 255 (1992), 850–853.

    Article  PubMed  CAS  Google Scholar 

  90. Shamraj, O. I., I. L. Grupp, G. Grupp, D. Melvin, N. Gradoux, W. Kremers, J. B. Lingrel, A. De Pover: Characterisation of Na/K-ATPase, its isoforms, and the inotropic response to ouabain in isolated failing human hearts. Cardiovasc. Res. 27 (1993), 2229–2237.

    Article  PubMed  CAS  Google Scholar 

  91. Sharma, V. K., L. A. Pottick, S. P. Banerjee: Ouabain stimulation of noradrenaline transport in guinea pig heart. Nature (Lond.) 386 (1980), 817–819.

    Article  Google Scholar 

  92. Shull, G. E., J. Greeb, J. B. Lingrel: Molecular cloning of three distinct forms of the Na+, K+-ATPase-α subunit from rat brain. Biochemistry 25 (1986), 8125–8132.

    Article  PubMed  CAS  Google Scholar 

  93. Smith, T. W.: Digoxin in heart failure. Editorial. New Engl. J. Med. 329 (1993), 51–53.

    Article  PubMed  CAS  Google Scholar 

  94. Somberg, J. C., T. W. Smith: Localization of the neurally mediated arrhythmogenic effects of digitalis. Science 204 (1979), 321–323.

    Article  PubMed  CAS  Google Scholar 

  95. Studer, R., H. Reinecke, J. Bilger, T. Eschenhagen, M. Boehm, G. Hasenfuss, H. J. Just, J. Holtz, H. Drexler: Gene expression of the cardiac Na+−Ca2+ exchanger in end-stage human heart failure. Circulat. Res. 75 (1994), 443–453.

    PubMed  CAS  Google Scholar 

  96. Taggart, A. J., G. D. Johnston, D. G. McDevitt: Digoxin withdrawal after cardiac failure in patients with sinus rhythm. J. cardiovasc. Pharmacol. 5 (1983), 229–234.

    CAS  Google Scholar 

  97. Tauke J., S. Goldstein, M. Gheorghiade: Digoxin for chronic heart failure: a review of the randomized controlled trials with special attention to the PROVED and RADIANCE trials. Prog. cardiovasc. Dis. 37 (1994), 49–58.

    Article  PubMed  CAS  Google Scholar 

  98. Tisdale, J. E., M. Gheorghiade: Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with heart failure. Amer. J. Cardiol. 69 (1992), 34G.

    Article  PubMed  CAS  Google Scholar 

  99. Urayama, O., H. Shutt, K. J. Sweadner: Identification of 3 isozyme proteins of the catalytic subunit of the Na,K-ATPase in rat brain. J. biol. Chem. 264 (1989), 8271–8280.

    PubMed  CAS  Google Scholar 

  100. Urayama, O., K. J. Sweadner: Quabain sensitivity of the alpha 3 isozyme of rat Na+, K+-ATPase. Biochem. biophys. Res. Commun. 156 (1988), 796–800.

    Article  PubMed  CAS  Google Scholar 

  101. Uretsky, B. F., J. B. Young, F. E. Shahidi, L. G. Yellen, M. C. Harrison, M. K. Jolly: Randomized study assessing the effects of digoxin withdrawal in patients with mild to moderate chronic congestive heartfailure: results of the PROVED trial. J. Amer. Coll. Cardiol. 22 (1993), 955–962.

    Article  CAS  Google Scholar 

  102. van Veldhuisen, D.J., A.J. Manin’t Veld, P.H.J.M. Dunselman, D. J. A. Lok, H.J.M. Dohmen, P.H.J.M. Poortermans, A. J. A. M. Withagen, W. H. Pasteuning, J. Brouwer, K. L. Liel: On behalf of the DIMT study group: digoxin in patients with mild to moderate heart failure. J. Amer. Coll. Cardiol. 63 (1993), D22-D25.

    Google Scholar 

  103. Vatner, S. F., C. B. Higgins, D. Franklin: Effects of a digitalis glycoside on coronary and systemic dynamics in conscious dogs. Circulat. Res. 28 (1971), 470.

    PubMed  CAS  Google Scholar 

  104. Wallick, E. T., A. Schwarz: Interaction of cardiac glycosides with Na+,K+-ATPase. Meth. Enzymol. 156 (1988), 201–213.

    Article  PubMed  CAS  Google Scholar 

  105. Wier, W. G., P. Hess: Excitation-contraction coupling in cardiac Purkinje fibres: effects of cardiotonic steroids on the intracellular [Ca2+) transient, membrane potential and contraction. J. gen. Physiol. 83 (1984), 395–415.

    Article  PubMed  CAS  Google Scholar 

  106. Wier, W. G.: Cytoplasmic (Ca2+) in mammalian ventricle: dynamic control by cellular processes. Ann. Rev. Physiol. 52 (1990), 467–485.

    Article  CAS  Google Scholar 

  107. Yusuf, S., R. Garg, P. Held: Need for a large trial to evaluate the effects of digitalis on morbidity and mortality in congestive heart failure. Amer. J. Cardiol. 69 (1992), 64G-70G.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Brigham and Women’s Hospital, Cardiovascular Division, Boston

    Thomas A. Fischer

  2. Klinik für Innere Medizin, Kardiologie, Krankenhaus Osnabrück, Osnabrück

    Norbert Treese

  3. Klinik für Innere Medizin/Kardiologie, Marienhospital, Johannisfreiheit 2-4, D-49074, Osnabrück

    Norbert Treese

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  1. Thomas A. Fischer
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  2. Norbert Treese
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Fischer, T.A., Treese, N. Stellenwert von Digitalis in der Therapie der akuten und chronischen Herzinsuffizienz. Med. Klin. 92, 546–551 (1997). https://doi.org/10.1007/BF03044930

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  • DOI: https://doi.org/10.1007/BF03044930

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