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Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts

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Summary

Using a modified Langendorff system, a special ECG recording technique and appropriate placement of two silver wire electrodes, early atrial and His bundle activity can be detected continuously from the surface of intact and spontaneously beating guinea pig hearts. This new method was applied to measure the direct and inhibitory effects of nifedipine and verapamil on impulse generation and conduction in isolated and perfused guinea pig hearts. Depression of sinoatrial conduction was the most prominent effect of nifedipine. In all concentrations applied (10−7 M, 10−6 M, 10−5 M) nifedipine predominantly led to sinoatrial blocks of different degrees. Heart rate decreased slightly in a dosedependent manner. PQ and HV duration remained essentially constant. In the highest concentration of nifedipine (10−5 M), sinus node activity was so depressed that AV dissociation or ventricular rhythm developed. Only in one out of eight experiments with cumulative increase of nifedipine concentrations to 10−5 M was the AV node affected by nifedipine and a second-degree AV block developed (10−6 M).

Verapamil's inhibitory effects on the rate of impulse initiation in the sinus node were more pronounced than those of nifedipine, but the inhibition of sinoatrial conduction by verapamil was less marked. At 10−6 M verapamil, the incidence of sinoatrial blocks and of ventricular rhythm was similar to the incidence of first degree AV blocks. PQ time (+14%) but also HV time (+12%) were prolonged under the influence of this concentration of verapamil. At the highest concentration of verapamil (10−5 M) applied for 10 min, ventricular rhythm developed in five out of eight experiments, as well as one second and two third-degree AV blocks.

The results confirm that the simultaneous measurement of sinus node activity of sinoatrial and atrioventricular conduction and of HV duration is feasible with this ECG technique, to evaluate the inhibitory effects of Ca-antagonists on sinus and AV node activity in the intact heart.

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References

  1. Angus JA, Richmond DR, Dhumma-Upakorn P, Cobbin LB, Goodman AH (1976) Cardiovascular action of verapamil in the dog with particular reference to the myocardial contractility and atrioventricular conduction. Cardiovasc Res 10:623–632

    PubMed  Google Scholar 

  2. Bender F (1967) Isoptin zur Behandlung der tachykarden Form des Vorhofflatterns. Med Klin 62:634–636

    PubMed  Google Scholar 

  3. Bender F (1970) Die Behandlung der tachykarden Arrhythmien und der arteriellen Hypertonie mit Verapamil. Arzneim-Forsch 20:1310–1316

    Google Scholar 

  4. Boothby CB, Garrard CS, Pickering D (1972) Verapamil in cardiac arrhythmias. Br Med J 2:348–349

    Google Scholar 

  5. Breithardt G, Seipel L, Wiebringhaus E, Loogan F (1978) Effects of verapamil on sinus node function in man. Europ J Cardiol 8/3:379–394

    Google Scholar 

  6. Breithardt G, Seipel L, Wiebringhaus E (1978) The sinus node. In: Bonke FJM (ed) Structure, function and clinical relevance. Martinus Nijhof Medical Division, Haag, pp 129–138

    Google Scholar 

  7. Fleckenstein A (1975) Adalat, a powerful Ca-antagonistic drug. 2nd International Adalat Symposium. In: Lochner W, Braasch W, Kroneberg G (eds) New therapy of Ischemic Heart Disease. Springer, Berlin Heidelberg New York, pp 56–65

    Google Scholar 

  8. Fleckenstein A (1980/1981) Pharmacology and electrophysiology of Ca-antagonists. In: Zanchetti A, Krikler DM (eds) Calcium Antagonism in Cardiovascular Therapy: Experience with Verapamil. International Symposium in Florence, October 2–4 1980. Excerpta Medica, Amsterdam Oxford Princeton, pp 10–29

    Google Scholar 

  9. Fleckenstein A (1981) Fundamental actions of calcium antagonists on myocardial and cardiac pacemaker cell membranes. In: Weiß GB (ed) New Perspectives on Calcium Antagonists, Clinical Physiology Scries. American Physiological Society. Bethesda, pp 59–81

    Google Scholar 

  10. Garvey HL (1969) The mechanism of action of verapamil on the sinus and AV nodes. Europ J Pharmacol 8:159–166

    Article  Google Scholar 

  11. Heng MK, Singh BN, Roche AHG, Norris RM, Mercer CJ (1975) Effects of intravenous verapamil on cardiac arrhythmias and on the ECG. Am Heart J 90:487–498

    Article  PubMed  Google Scholar 

  12. Henry PD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047–1058

    PubMed  Google Scholar 

  13. Husaini MH, Kvasnicka J, Ryden L, Holmberg S (1973) Action of verapamil on sinus node, atrioventricular and intraventricular conduction. Br Heart J 35:734–737

    PubMed  Google Scholar 

  14. Kawai CH, Konishi T, Matsuyama E, Okazaki H (1981) Comparative effects of three calcium antagonists, diltiazem, verapamil and nifedipine, on the sinoatrial and atrioventricular nodes; experimental and clinical studies. Circulation 5:1035–1042

    Google Scholar 

  15. Krikler D, Spurrell RA (1974) Verapamil in the treatment of paroxysmal supraventricular tachycardia. Postgrad Med J 50:447–453

    PubMed  Google Scholar 

  16. Lathrop DA, Valle-Aguilera JR, Millard RW, Gaum WE, Hannon DW, Francis PD, Nakaya H, Schwartz A (1982) Comparative electrophysiologic and coronary hemodynamic effects of diltiazem, nisoldipine and verapamil on myocardial tissue. Am J Cardiol 49:613–620

    PubMed  Google Scholar 

  17. Mitchell LB, Schroeder JS, Mason JW (1982) Comparative clinical electrophysiologic effects of diltiazem, verapamil and nifedipine: a review. Am J Cardiol 49:629–635

    PubMed  Google Scholar 

  18. Narimatsu A, Taira N (1976) Effects on atrio-ventricular conduction of calcium-antagonistic coronary vasodilators, local anaesthetics and quinidine injected into the posterior and the anterior septal artery of the atrio-ventricular node preparation of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 294:169–177

    Article  Google Scholar 

  19. Neuß H, Schlepper M (1971) Der Einfluß von Verapamil auf die atrio-ventrikuläre Überleitung. Lokalisation des Wirkungsortes mit His-Bündel-Elektrogrammen. Verh Deutsch Ges Kreislaufforsch 37:433–438

    PubMed  Google Scholar 

  20. Pop T, Treese N, Kasper W, Meinertz T, Schuster CJ, Schreiner G, Meyer J (1983) Die Wirkung von Nifedipin auf die Sinusknoten- und AV-Knotenfunktion unter autonomer Blockade beim Menschen. Z Kardiol 72:735–739

    PubMed  Google Scholar 

  21. Raschack M (1976) Differencies in the cardiac actions of the calcium antagonists verapamil and nifedipine. Arzneim-Forsch 26:1330–1333

    Google Scholar 

  22. Rosen MR, Wit AL, Hoffman BF (1975) Electrophysiology and pharmacology of cardiac arrhythmias. VI. Cardiac effects of verapamil. Am Heart J 89/5:665–673

    Article  Google Scholar 

  23. Rowland E, Evens T, Krikler D (1979) Effect of nifedipine on atrioventricular conduction as compared with verapamil. Br Heart J 42:124–127

    PubMed  Google Scholar 

  24. Roy PR, Spurrell RAJ, Sowton E (1974) The effect of verapamil on the cardiac conduction in man. Postgrad Med 50:270–275

    Google Scholar 

  25. Satoh K, Yanagisawa T, Taira N (1979) Effects on atrioventricular conduction and blood flow of enantiomers of verapamil and of tetrodotoxin injected into the posterior and the anterior septal artery of the AV-node preparation of the dog. Naunyn-Schmiedeberg's Arch Exp Pathol Pharmacol 308:89–98

    Article  Google Scholar 

  26. Stark G, Huber U, Hofer E, Tritthart HA. Continuous ECG measurements of intracardiac activities from the surface of Langendorff-perfused guinea pig hearts. Basic Res Cardiol, in press

  27. Taira N, Narimatsu A (1975) Effects of nifedipine, a potent calcium-antagonistic coronary vasodilator, on atrioventricular conduction and blood flow in the isolated atrioventricular node preparation of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 290:107–112

    Article  Google Scholar 

  28. Tritthart HA, Fleckenstein B, Fleckenstein A (1971) Some fundamental actions of antiarrhythmic drugs on the excitability and the contractility of single myocardial fibers. Naunyn-Schmiedeberg's Arch Exp Pathol Pharmacol 269:212

    Google Scholar 

  29. Tritthart HA (1977) Die medizinische Therapie der Erregungsbildungs- und Erregungsleitungsstörungen. Die elektrophysiologischen Grundlagen. In: Reindell H, Roskamm H (Hrsg) Herzkrankheiten, Pathophysiologie, Diagnostik, Therapie, Springer, Berlin Heidelberg New York

    Google Scholar 

  30. Tritthart HA (1979) Über das Wirkspektrum von Antiarrhythmika. In: Antoni H, Bender F, Gerlach E, Schlepper M (Hrsg) Herzrhythmusstörungen. Neue theoretische und klinische Aspekte. FK Schattauer, Stuttgart New York, S 313–325

    Google Scholar 

  31. Wit AL, Cranefield PF (1974) Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanism by which it arrests reentrant atrioventricular nodal tachycardia.Circ Res 35:413–425

    PubMed  Google Scholar 

  32. Zipes DP, Fischer JC (1974) Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in dog. Circ Res 34:184–192

    PubMed  Google Scholar 

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Author notes

  1. G. Stark

    Present address: Institute of Medical Physics and Biophysics, University of Graz, Harrachgasse 21, 8010, Graz, Austria

Authors and Affiliations

  1. Institute of Medical Physics and Biophysics, University of Graz, Harrachgasse 21, 8010, Graz, Austria

    U. Stark & H. A. Tritthart

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Additional information

Research scholarship of the Ministry for Science and Research

Preliminary results were published at the “Jahrestagung der Dt. Gesellschaft für Pharmakologie und Toxikologie” (Naunyn-Schmiedeberg's Archives of Pharmacology)

Supported by a grant of the Ministry for Science and Research, Program for the Reduction of Animal Experiments, Austria

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Stark, G., Stark, U. & Tritthart, H.A. Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts. Basic Res Cardiol 83, 202–212 (1988). https://doi.org/10.1007/BF01907274

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  • DOI: https://doi.org/10.1007/BF01907274

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