The Electrophysiologic Differences of Calcium Antagonist Drugs

  • L. Seipel
  • G. Breithardt
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 18)

Abstract

In 1967, FLECKENSTEIN et al (27) assumed that the new compounds prenylamine and verapamil were inhibitors of the action of calcium. The concept that these so-called Ca-antagonists are inhibitors of the slow channel, is now widely accepted (16, 46, 61, 88, 100). These drugs are affecting structures in which impulse propagation is mediated by the slow channel, i.e. the sinus and A-V node. In addition, they may depress action potentials and slow conduction in diseased myocardial or Purkinje fibers. As a consequence, SINGH and VAUGHAN WILLIAMS (90) postulated a new class of antiarrhythmic action (class 4). However, some recent investigations have questioned this uniform concept for all Ca-antagonists (3, 15, 21, 28, 42, 48, 61, 62, 88). In the following paper the electrophysio-logic differences will be discussed with regard to experimental and clinical studies.

Keywords

Cardiol Propranolol Verapamil Nifedipine Rosen 

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References

  1. 1.
    Angus JA, Richmond DR, Dhuma-Upakorn P, Kobbin LB, Goodman AH. Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and at rioventricular conduction. Cardiovasc Res 1976; 10: 623–632.PubMedCrossRefGoogle Scholar
  2. 2.
    Bass O, Friedmann M. Ein Beitrag zum antiarrhythmischen Wirkungsmechanismus von Verapamil (Isoptin). Schweiz Med Wschr 1971; 101: 792–799.PubMedGoogle Scholar
  3. 3.
    Bayer R, Kalusche D, Kaufmann R, Mannhold R. Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. III. Effects of the optical isomers on the transmembrane action potentials. Naunyn-Schmiedeberg’s Arch Pharmacol 1975;290: 81–97.CrossRefGoogle Scholar
  4. 4.
    Beck OA, Witt E, Lehmann H-U, Hochrein H. Die Wirkung von Gallopamil (D 600) auf die intrakardiale Erregungsleitung und Sinusknotenautomatie beim Menschen. Z Kardiol 1978;67: 522–526.PubMedGoogle Scholar
  5. 5.
    Belz GG, Bender F. 1974. Therapie der Herzrhythmusstörungen mit Verapamil. Stuttgart, Fischer, pp 8–13.Google Scholar
  6. 6.
    Bischoff KO, Hager W, Flohr E, Heredia D. Die Beeinflussung systolischer und elektrokardiographischer Zeitintervalle herzgesunder Patienten durch den Kalziumantagonisten Ro 11-1781. Z Kardiol 1978;67: 268–272.PubMedGoogle Scholar
  7. 7.
    Blömer H, Wirtzfeld A, Delius W, Sebening H. 1977. Das Sinusknotensyndrom. Erlangen, Perimed, p 89.Google Scholar
  8. 8.
    Bödeker K, Bischoff KO, Menken U, Hager W. Hämodynamisehe und elektrophysiologisehe Wirkungen des neuen Calcium-Antagonisten Ro 11-1781. Z Kardiol 1980;69:790–796.PubMedGoogle Scholar
  9. 9.
    Breithardt G, Scipel L. 1976. The influence of drugs on sinoatrial conduction time in man; in Lüderitz: Cardiac pacing. Berlin, Springer, pp 58–72.Google Scholar
  10. 10.
    Breithardt G, Scipel L, Wiebringhaus E, Loogen F. Effects of verapamil on sinus node function in man. Europ J Cardiol 1978;8:379–394.Google Scholar
  11. 11.
    Breithardt G, Scipel L, Wiebringhaus E, Loogen F. The role of autonomie nervous system in the action of verapamil on the sinus node in man. Basic Res Cardiol 1978;73:637–647.PubMedCrossRefGoogle Scholar
  12. 12.
    Broks WW, Verrier RL, Lown B. Protective effect of verapamil on ventricular vulnerability during coronary artery occlusion and reperfusion (Abstr.). Am J Cardiol 1978;41:426.CrossRefGoogle Scholar
  13. 13.
    Carrasco HA, Fuenmayor A, Barboza JS, Gonzales G. Effect of verapamil on normal sinoatrial node function and on sick sinus syndrome. Am Heart J 1978;96: 760–771.PubMedCrossRefGoogle Scholar
  14. 14.
    Cavero I, Boudot JP, Lefevre-Borg F, Roach AG. 1979. Pharmacological evaluation of diltiazem and its desacetylated metabolite in several animal species. III. Mechanism of the cardiac acceleration evoked by diltiazem and desacetyldi1tiazem in the conscious rabbit; in Bing: New drug therapy with a calcium antagonist. Amsterdam, Excerpta Medica, pp 81–88.Google Scholar
  15. 15.
    Chiba S, Kobayashi M, Furukawa Y. Effects of optical isomers of verapamil on SA nodal pacemaker activity and contractility of the isolated dog heart. Jap Heart J 1978; 19:409–414.PubMedCrossRefGoogle Scholar
  16. 16.
    Cranefield PF, Aronson RS, Wit AL. Effect of Verapamil on the normal action potential and on a calcium depent slow response of canine cardiac purkinje fibers. Circulation Res 1974; 34: 204–213.PubMedGoogle Scholar
  17. 17.
    Dangman KH, Hoffman BF. Effects of nifedipine on electrical activity of cardiac cells. Am J Cardiol 1980;46:1059–1067.PubMedCrossRefGoogle Scholar
  18. 18.
    Danilo P Jr, Hordof AJ, Reder RF, Rosen MR. Effects of verapamil on electrophysiologic properties of blood superfused cardiac purkinje fibers. J Pharmacol and Exper Therap 1980; 213:222–227.Google Scholar
  19. 19.
    Dighton DH. Sinus Bradycardia. Autonomic influences and clinical assessment. Brit Heart J 1974;36: 791–797.PubMedCrossRefGoogle Scholar
  20. 20.
    Dyrszka H, Wahn B. Klinisches Bild und Therapie einer Überdosis des Koronartherapeutikums Nifedipine (Adalat). Inn Med 1977;4:31–34.Google Scholar
  21. 21.
    Ehara T, Kaufmann R. The voltage-and time-dependent effects of (-)-verapami1 on the slow inward current in isolated cat ventricular myocardium. J Pharmacol exper Ther 1978;207:49–55.Google Scholar
  22. 22.
    Elharrar V, Gaum WE, Zipes DP. Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs. Am J Cardiol 1977; 39: 544–549.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Sherif N, Lazzara R. Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of “slow channel”. Circulation 1979; 60:605–615.PubMedGoogle Scholar
  24. 24.
    Endoh M, Yanagisawa T, Taira N. Effects of Calcium-Antagonistic Coronary Vasodilators. Nifedipine and Verapamil, on Ventricular Automaticity of the Dog. Naunyn-Schmiedeberg’s Arch Pharmacol 1978;302:235–238.CrossRefGoogle Scholar
  25. 25.
    Faire U de, Lundman T. Attempted suicide with verapamil. Europ J Cardiol 1977; 6:195–198.Google Scholar
  26. 26.
    Feerst D, Talano J, Singer D, Lesch M. The effect of verapamil on latent pacemakers in the canine heart (Abstr.). Circulation Suppl 1978; 58/II:183.Google Scholar
  27. 27.
    Fleckenstein A, Kammermeier H, Döring H, Freund HJ. Zum Wirkungsmechanismus neuartiger Koronardi1 atatoren mit gleichzeitig Sauerstoff-einsparenden Myokard-Effekten, Prenylamin und Iproveratril. Z Kreisl Forschg 1967;56:716–744.Google Scholar
  28. 28.
    Fleckenstein A, Späh F. 1981. Excitation-contraction uncoupling in the cardiac muscle; in Ebashi (ed.): Proc 8th intern Congr Pharmacol. London, Pergamon Press, p 23.Google Scholar
  29. 29.
    Fondacaro JD, Han J, Yoon MS. Effects of verapamil on ventricular rhythm during acute coronary occlusion. Am Heart J 1978;96: 81–86.PubMedCrossRefGoogle Scholar
  30. 30.
    Garvey HL. The mechanisms of action of verapamil on the sinus and AV nodes. Europ J Pharmacol 1969;8:159–166.CrossRefGoogle Scholar
  31. 31.
    Gleichmann U, Scipel L, Loogen F. Der Einfluß von Anti-arrhythmika auf die intrakardiale Erregungsleitung (His-Bündel Elektrographie) und Sinusknotenautomatie beim Menschen. Dtsch Med Wschr 1973;98:1487–1494.PubMedCrossRefGoogle Scholar
  32. 32.
    Gmeiner R, Simma H, Ng CK, Dienstl F, Knapp E. Die Wirkung von Ro 11-1781, einem Kaiziumantagonisten, auf die atrioventri-kuläre Überleitung. Z Kardiol 1977;66: 238–241.PubMedGoogle Scholar
  33. 33.
    Gmeiner R, Ng CK, Simma H, Gstöttner M. The effect of a new calcium antagonist (Ro 11-1781) on the cardiac conduction system in man. Europ J Cardiol 1979;9:77–86.Google Scholar
  34. 34.
    Gmeiner R, Ng CK. Effect of tiapamil in the Wolff-Parkinson-White syndrome. J Cardiovasc Pharmacol 1981;3:237–250.PubMedCrossRefGoogle Scholar
  35. 35.
    Grendahl H, Miller M, Sivertssen E. Registration of sinus node recovery time in patients with sinus rhythm and in patients with disrhythmias. Act Med Scand 1975; 197: 403–408.CrossRefGoogle Scholar
  36. 36.
    Grohmann HW, Theisen K, Jahrmärker H. Einfach-und Doppelstimulation des menschlichen Vorhofs. Untersuchungen zur Refraktärzeitbestimmung. Verh Dtsch Ges Kreislaufforschg 1971; 37:460–464.Google Scholar
  37. 37.
    Heng MK, Singh BN, Roche AHG, Norris RM, Mercer CJ. Effects of intravenous verapamil on cardiac arrhythmias and on the electrocardiogram. Am Heart J 1975; 90:487–498.PubMedCrossRefGoogle Scholar
  38. 38.
    Hordof AJ, Edie R, Malm JR, Hoffman BF, Rosen MR. Electrophy-siologic properties and response to pharmacologic agents of fibers from diseased human atria. Circulation 1976; 54: 774–779.PubMedGoogle Scholar
  39. 39.
    Husaini MH, Kvasnicka J, Ryden L, Holmberg S. Action of verapamil on sinus node, atrioventricular und intraventri cular conduction. Br Heart J 1973; 35: 734–737.PubMedCrossRefGoogle Scholar
  40. 40.
    Iijima T, Taira N. Modification by manganese ions and verapamil of the responses of the atrioventricular node to norepinephrine. Europ J Pharmacol 1976;37:55–62.CrossRefGoogle Scholar
  41. 41.
    Kaltenbach M, Hopf R, Keller M. Calciumantagonistisehe Therapie bei hypertrophisch-obstruktiver Kardiomyopathie. Dtsch Med Wschr 1976;101:1284–1287.PubMedCrossRefGoogle Scholar
  42. 42.
    Kaufmann R, Bayer R. 1980. Combination of ß-Blockers and calcium antagonists with regard to cardiac electrophysiology; in Roskomm, Graefe: Advances in ß-Blocker therapy. Amsterdam, Excerpta Medica, pp 111–119.Google Scholar
  43. 43.
    Kaufmann AJ, Aramendia P. Prevention of ventricular fibrillation induced by coronary ligat ion. J Pharmacol Exper Ther 1968;164:326–332.Google Scholar
  44. 44.
    Kawai C, Konishi T, Matsuyama E, Okazaki H. 1979. Effects of diltiazem on sinoatrial and atrioventricular nodes in comparison with other calcium-antagonists; in Bing: New drug therapy with a calcium antagonist. Amsterdam, Excerpta Medica, pp 141–149.Google Scholar
  45. 45.
    Klempt HW, Bachour G, Reploh HD, Gradaus D, Brisse B, Bender F. Untersuchungen zum Wirkungsmechanismus von Verapamil. Verh Dtsch Ges inn Med 1972;78:1116–1120.PubMedGoogle Scholar
  46. 46.
    Kohlhardt M, Bauer B, Kraise H, Fleckenstein A. Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibers by use of specific inhibitors. Pfluegers Archiv 1972;335:309–322.PubMedCrossRefGoogle Scholar
  47. 47.
    Kohlhardt M, Figulla HR, Tripathi O. The slow membrane channel as the predominant mediator of the excitation process of the sinoatrial pacemaker cell. Basic Res Cardiol 1976;71:17–26.PubMedCrossRefGoogle Scholar
  48. 48.
    Kohlhardt M, Fleckenstein A. Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn Schmiedeberg’s Arch Pharmacol 1977; 298: 267–272.CrossRefGoogle Scholar
  49. 49.
    Kuhn H, Thelen U, Leuner C, Köhler E, Bluschke V. Langzeitbehandlung der hypertrophischen nicht obstruktiven Kar-diomyopathie (HNCM) mit Verapamil. Z Kardiol 1980; 69: 669–675.PubMedGoogle Scholar
  50. 50.
    Kupersmith J, Cohen R. Differing electrophysiologic effects of slow response inhibiting agents manganese and verapamil on ischemic, infarcted and normal tissue in situ. J Pharmacol exper Ther 1980; 215: 394–400.Google Scholar
  51. 51.
    Landmark K, Amlie JP. A study of the verapamil-induced changes in conductivity and refractoriness and monophasic action potentials of the dog heart in situ. Europ J Cardiol 1976; 4: 419–427.Google Scholar
  52. 52.
    Lupi GA, Urthaler F, James TN. Effects of verapamil on automaticity and conduction with particular reference to tachyphylaxis. Europ J Cardiol 1979;9:345–368.Google Scholar
  53. 53.
    Mancia G, Bonazzi O, Ferrari A, Gardumi M, Gregorini L, Perondi R, Pozzoni L. 1978. Baroreceptor control of atrio-ventricular conduction system in man; in Scharz, Brown, Malliani, Zanetti: Neural mechanisms in cardiac arrhythmias. New York, Raven-Presse, pp 339–343.Google Scholar
  54. 54.
    Mandel WJ, Hayakawa H, Allen HN, Danzig R, Kermaier AI. Assessment of sinus node function in patients with the sick sinus syndrome. Circulation 1972;46: 761–769.PubMedGoogle Scholar
  55. 55.
    Mangiardi LM, Hariman RJ, McAllister RG, Bhargava V, Surawicz B, Shabetal R. Electrophysiologic and hemodynamic effects of Verapamil. Circulation 1978; 57: 366–372.PubMedGoogle Scholar
  56. 56.
    Matsuyama E, Konishi T, Okazaki H, Matsuda H, Kawai C. Effects of verapamil on accessory pathway properities and induction of circus movement tachycardia in patients with the Wolff-Parkinson-White syndrome. J Cardiovasc Pharmacol 1981; 3: 11–24.PubMedCrossRefGoogle Scholar
  57. 57.
    Melville KI, Shister HE, Huo S. Iproveratril: Experimental data on coronary dilatation and antiarrhythmic action. Canad Med Ass 1964; 90: 761–770.Google Scholar
  58. 58.
    Mertens HM, Mannebach H, Gleichmann U. 24stündiger elektrischer Herzstillstand nach intravenöser Gabe von 10 mg Verapamil. Z Kardiol 1980; 69: 414–416.PubMedGoogle Scholar
  59. 59.
    Motomura S, Taira N. Differential effects of organic slow inward current inhibitors, verapamil and nifedipine, on rate of atrioventricu1ar rhythm and supra ventri cular tachycardia in the canine isolated, blood perfused AV node preparation. Naunyn-Schmiedeberg’s Arch Pharmacol 1981; 315: 241–248.CrossRefGoogle Scholar
  60. 60.
    Narimatsu A, Taira N. Effects on atrio-ventricul ar conduction of calcium-antagonistic coronary vasodilators, local anaesthetics and quinidine injected into the posterior and septal artery of the atrioventricular node preparation of the dog. Naunyn-Schmiedeberg’s Arch Pharmacol 1976; 294:169–177.CrossRefGoogle Scholar
  61. 61.
    Nawrath H, Ten Eick RE, McDonald TF, Trautwein W. On the mechanism underlying the action of D-600 on slow inward current and tension in mammalian myocardium. Circulation Res 1977;40: 408–414.PubMedGoogle Scholar
  62. 62.
    Nayler WG. Calcium antagonists. Europ Heart J 1980; 1:225–237.Google Scholar
  63. 63.
    Neuss H, Schlepper M. Der Einfluß von Verapamil auf die atrio-ventrikul äire Überleitung. Lokalisation des Wirkungsortes mit His-Bündel Elektrogrammen. Verh Dtsch Ges Kreisl Forschg 1971; 37: 433–438.Google Scholar
  64. 64.
    Neuss H, Schlepper M. Influence of verious antiarrhythmic drugs (Aprinidine, Ajma line, Verapamil, Oxprenolol, Orciprenaline) on functional properties of accessory A-V pathway. Act Cardiol Suppl 1974; 18: 279–288.Google Scholar
  65. 65.
    Obayashi K, Nagasawa K, Mandel WJ, Vyden JK. Cardiovascular effects of the new antiarrhythmic agent verapamil (Abstr.). Am J Cardiol 1975;35:161.CrossRefGoogle Scholar
  66. 66.
    Okada T, Konishi T. Effects of verapamil on SA and AV nodal action potentials in the isolated rabbit heart. Jap Circulation J 1975; 39: 913–917.CrossRefGoogle Scholar
  67. 67.
    Ono H, Himori N, Taira N. Chronotropic effects of coronary vasodilators as assessed in the isolated, blood-perfused sinoatrial node preparation of the dog. Tohoki J exp Med 1977; 121:383–390.CrossRefGoogle Scholar
  68. 68.
    Oyama Y, Imai Y, Nakaya H, Kanda K, Satoh T. The effects of diltiazem hydrochloride on the cardiac conduction. A clinical study of His bundle electrogram. Jap Circulation J 1978; 42: 1257–1264.CrossRefGoogle Scholar
  69. 69.
    Padeletti L, Franchi F, Brat A, Dabizzi RP, Michelucci A. The cardiac electrophysiological effects of nifedipine. Intern J Clin Pharmacol Biopharm 1979; 17:290–293.Google Scholar
  70. 70.
    Perkins CM. Serious verapamil poisoning: treatment with intravenous calcium gluconate. Brit Med J 1978; 4:1127.CrossRefGoogle Scholar
  71. 71.
    Peter T, Hamamoto H, McCullen A, Yamaguchi I, Mandel WJ. 1980. Verapamil effects in the setting of acute experimental myocardial ischemia; in Fleckenstein, Roskamm: Calcium-Antagonismus. Berlin, Springer, pp 75–85.Google Scholar
  72. 72.
    Raschack M. Differences in the cardiac actions of the Calcium antagonists Verapamil and Nifedipine. Arzneim Forschg 1976; 26: 1330–1333.Google Scholar
  73. 73.
    Refsum H, Landmark K. The effect of a Calcium-antagonistic drug, nifedipine, on the mechanical and electrical activity of the isolated rat atrium. Act pharmacol toxical (Kbh) 1975; 37: 369–376.CrossRefGoogle Scholar
  74. 74.
    Refsum H, Glomstein A, Landmark K. The effect of nifedipine on the isolated rat heart. Act pharmacol toxicol (Kbh) 1976; 38:328–335.Google Scholar
  75. 75.
    Ribeiro LGT, DeBauche TL, Brandon TA, Maroko PR, Miller RR. Comparative effects of verapamil and nifedipine on reactive hyperemia and ventricular arrhythmias during coronary reperfusion. Europ Heart J 1980;1, suppl B: 31–35.Google Scholar
  76. 76.
    Rinkenberger RL, Prystowsky EN, Heger JJ, Troup PJ, Jackman WM, Zipes DP. Effects of intravenous and chronic oral verapamil administration in patients with supraventricular tachyarrhythmias. Circulation 1980; 62: 996–1010.PubMedGoogle Scholar
  77. 77.
    Rizzon P, DiBiase M, Calabrese P, Brindicci G, Chiddo A. Electrophysiologic evaluation of intravenous verapamil in man. Europ J Cardiol 1977; 6:179–194.Google Scholar
  78. 78.
    Rosen MR, Ilvento JP, Gelband H, Merker C. Effects of verapamil on electrophysiologic properties of canine cardiac purkinje fibers. J Pharmacol exper Ther 1974; 189: 414–422.Google Scholar
  79. 79.
    Ross G, Jorgensen CR. Cardiovascular actions of verapamil. J Pharmacol exper Ther 1967; 158: 504–509.Google Scholar
  80. 80.
    Rossner KL, Sachs HS. Electrophysiological study of Syrian hamster hereditary cardiomyopathy. Cardiovasc Res 1978; 12: 436–443.PubMedCrossRefGoogle Scholar
  81. 81.
    Rowland E, Evans T, Krikler D. Effect of nifedipine on atrioventricular conduction as compared with verapamil. Intracardiac electrophysiological study. Br Heart J 1979;42:124–127.PubMedCrossRefGoogle Scholar
  82. 82.
    Roy PR, Spurrel RAJ, Sowton E. The effect of verapamil on the cardiac conduction system in man. Postgrad Med J 1974; 50: 270–275.CrossRefGoogle Scholar
  83. 83.
    Saikawa T, Arita M. Effects of verapamil and its optical isomers on repetitive slow responses induced by electrical depolarization in canine ventricular myocardium. Jap Heart J 1980; 21:247–255.PubMedCrossRefGoogle Scholar
  84. 84.
    Schlepper M, Neuss H. Changes of refractory periods in the A-V conduction system induced by antiarrhythmic drugs. A study using His bundle recordings. Act Cardiol (Brux) 1974;suppl 18: 269–277.Google Scholar
  85. 85.
    Scipel L, Breithardt G. 1980. Effects of Calcium-antagonists on automaticity and conduction in man; in Fleckenstein, Roskamm: Calcium-Antagonismus. Berlin, Springer, pp 87–96.Google Scholar
  86. 86.
    Scipel L, Both A, Breithardt G, Gleichmann U, Loogen F. Action of antiarrhythmic drugs on His bundle electrogram and sinus node function. Act Cardiol (Brux) 1974; suppl 18:251–267.Google Scholar
  87. 87.
    Scipel L, Breithardt G, Abendroth, R-R, Wiebringhaus E. Vergleichende klinisch-elektrophysiologische Untersuchungen verschiedener Ca-Antagonisten (Gallopamil (D 600), Dimeditia-pramin (Ro 11-1781), Verapamil). Z Kardiol 1980; 69: 551–555.Google Scholar
  88. 88.
    Shigenobu K, Schneider JA, Sperelakis N. Verapamil blockade of slow Na+ and Ca+ responses in myocardial cells. J Pharmacol exper Ther 1974; 190: 280–288.Google Scholar
  89. 89.
    Silvertssen E, Bay G, Grendahl H. The effect of propranolol and verapamil on atrial and at rioventricular refractory periods in man. Angiol 1975; 26:605–618.CrossRefGoogle Scholar
  90. 90.
    Singh BN, Vaughan Williams EM. A fourth class of antidysrhythmic action? Effect of verapamil on ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function. Cardiovasc Res 1972; 6: 109–119.PubMedCrossRefGoogle Scholar
  91. 91.
    Spurrell RAJ, Krikler DM, Sowton E. Effects of verapamil on electrophysiological properties of anomalous atrioventricular connexion in Wolff-Parkinson-White-syndrome. Br Heart J 1974; 36:256–264.PubMedCrossRefGoogle Scholar
  92. 92.
    Sugimoto T, Ishikawa T, Kaseno K, Nakase S. Electrophysiological effects of diltiazem, a calcium antagonist, in patients with impaired sinus or atrioventricular node function. Angiol 1980; 31: 700–709.CrossRefGoogle Scholar
  93. 93.
    Sugiyama S, Ozawa T, Suzuki S, Kato T. Effects of verapamil and propranolol on ventricular vulnerability after coronary reperfusion. J Electrocardiol 1980; 13: 49–54.PubMedCrossRefGoogle Scholar
  94. 94.
    Tse WW, Han J. Effect of manganese chloride and verapamil on automaticity of digitalized purkinje fibers. Am J Cardiol 1975; 36: 50–55.PubMedCrossRefGoogle Scholar
  95. 95.
    Urthaler F, James TN. Experimental studies on the pathogenesis of asystole after verapamil in the dog. Am J Cardiol 1979; 44: 651–656.PubMedCrossRefGoogle Scholar
  96. 96.
    Wellens HJJ. 1975. Effect of Drugs on Wolff-Parkinson-White syndrome; in Narula: His bundle electrography and clinical electrophysiology. Philadelphia, Davis Comp., pp 367–385.Google Scholar
  97. 97.
    Wit AL, Cranefield PF. Effect of Verapamil on the sinoatrial and atrioventri cular nodes of the rabbit and the mechanism by which it arrests reentrant atrioventri cular node tachycardia. Circulation Res 1974; 35: 413–425.PubMedGoogle Scholar
  98. 98.
    Wit AL, Fenoglio JJ, Hordorf AJ, Reemtsma K. Ultrastructure and transmembrane potentials of cardiac muscle in the human anterior mitral valve leaflet. Circulation 1979; 59:1284–1292.PubMedGoogle Scholar
  99. 99.
    Yamaguchi I, Obayashi K, Mandel WJ. Electrophysiological effects of verapamil. Cardiovasc Res 1978; 12: 597–608.PubMedCrossRefGoogle Scholar
  100. 100.
    Zipes DP, Fischer JC. Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventri cular conduction in the dog. Circulation Res 1974;34:184–192.PubMedGoogle Scholar

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© Martinus Nijhoff Publishers, The Hague 1982

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  • L. Seipel
  • G. Breithardt

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