Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Mar;81(3):688–699. doi: 10.1172/JCI113374

Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias.

R J Sung 1, E C Keung 1, N X Nguyen 1, E C Huycke 1
PMCID: PMC442516  PMID: 2893808

Abstract

To assess effects of beta-adrenergic blockade on ventricular tachycardia (VT) of various mechanisms, electrophysiology studies were performed before and after intravenous infusion of propranolol (0.2 mg/kg) in 33 patients with chronic recurrent VT, who had previously been tested with intravenous verapamil (0.15 mg/kg followed by 0.005 mg/kg/min infusion). In the verapamil-irresponsive group, 10 patients (group IA) had VT that could be initiated by programmed ventricular extrastimulation and terminated by overdrive ventricular pacing, and 11 patients (group IB) had VT that could be provoked by isoproterenol infusion (3-8 micrograms/min) but not by programmed electrical stimulation, and that could not be converted to a sustained sinus rhythm by overdrive ventricular pacing. Notably, in the group IA patients, all 10 patients had structural heart disease (coronary arteriosclerosis or idiopathic cardiomyopathy); beta-adrenergic blockade accelerated the VT rate in one patient but exerted no effects on the VT rate in the remaining 9 patients, and VT remained inducible in all 10 patients. By contrast, in the group IB patients, 7 of the 11 patients had no apparent structural heart disease; beta-adrenergic blockade completely suppressed the VT inducibility during isoproterenol infusion in all 11 patients. There were 12 patients with verapamil-responsive VT (group II). 11 of the 12 patients had no apparent structural heart disease. In these patients, the initiation of VT was related to attaining a critical range of cycle lengths during sinus, atrial-paced or ventricular-paced rhythm; beta-adrenergic blockade could only slow the VT rate without suppressing its inducibility. Of note, 14 of the total 33 patients had exercise provocable VT: two in group IA, five in group IB, and seven in group II. Thus, mechanisms of VT vary among patients, and so do their pharmacologic responses. Although reentry, catecholamine-sensitive automaticity, and triggered activity related to delayed afterdepolarizations are merely speculative, results of this study indicate that beta-adrenergic blockade is only specifically effective in a subset group (group IB) of patients with VT suggestive of catecholamine-sensitive automaticity.

Full text

PDF
688

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson R. S. Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension. Circ Res. 1981 May;48(5):720–727. doi: 10.1161/01.res.48.5.720. [DOI] [PubMed] [Google Scholar]
  2. Aronson R. S., Gelles J. M. The effect of ouabain, dinitrophenol, and lithium on the pacemaker current in sheep cardiac Purkinje fibers. Circ Res. 1977 May;40(5):517–524. doi: 10.1161/01.res.40.5.517. [DOI] [PubMed] [Google Scholar]
  3. Bean B. P., Nowycky M. C., Tsien R. W. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells. 1984 Jan 26-Feb 1Nature. 307(5949):371–375. doi: 10.1038/307371a0. [DOI] [PubMed] [Google Scholar]
  4. Belhassen B., Shapira I., Pelleg A., Copperman I., Kauli N., Laniado S. Idiopathic recurrent sustained ventricular tachycardia responsive to verapamil: an ECG-electrophysiologic entity. Am Heart J. 1984 Oct;108(4 Pt 1):1034–1037. doi: 10.1016/0002-8703(84)90475-7. [DOI] [PubMed] [Google Scholar]
  5. Borer J. S., Bacharach S. L., Green M. V., Kent K. M., Epstein S. E., Johnston G. S. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease. N Engl J Med. 1977 Apr 14;296(15):839–844. doi: 10.1056/NEJM197704142961503. [DOI] [PubMed] [Google Scholar]
  6. Brum G., Flockerzi V., Hofmann F., Osterrieder W., Trautwein W. Injection of catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes. Pflugers Arch. 1983 Jul;398(2):147–154. doi: 10.1007/BF00581064. [DOI] [PubMed] [Google Scholar]
  7. Brum G., Osterrieder W., Trautwein W. Beta-adrenergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pflugers Arch. 1984 Jun;401(2):111–118. doi: 10.1007/BF00583870. [DOI] [PubMed] [Google Scholar]
  8. Buxton A. E., Waxman H. L., Marchlinski F. E., Simson M. B., Cassidy D., Josephson M. E. Right ventricular tachycardia: clinical and electrophysiologic characteristics. Circulation. 1983 Nov;68(5):917–927. doi: 10.1161/01.cir.68.5.917. [DOI] [PubMed] [Google Scholar]
  9. Cardinal R., Savard P., Carson D. L., Perry J. B., Pagé P. Mapping of ventricular tachycardia induced by programmed stimulation in canine preparations of myocardial infarction. Circulation. 1984 Jul;70(1):136–148. doi: 10.1161/01.cir.70.1.136. [DOI] [PubMed] [Google Scholar]
  10. DOAN A. E., PETERSON D. R., BLACKMON J. R., BRUCE R. A. MYOCARDIAL ISCHEMIA AFTER MAXIMAL EXERCISE IN HEALTHY MEN. A METHOD FOR DETECTING POTENTIAL CORONARY HEART DISEASE? Am Heart J. 1965 Jan;69:11–21. doi: 10.1016/0002-8703(65)90211-5. [DOI] [PubMed] [Google Scholar]
  11. Dangman K. H., Danilo P., Jr, Hordof A. J., Mary-Rabine L., Reder R. F., Rosen M. R. Electrophysiologic characteristics of human ventricular and Purkinje fibers. Circulation. 1982 Feb;65(2):362–368. doi: 10.1161/01.cir.65.2.362. [DOI] [PubMed] [Google Scholar]
  12. El-Sherif N., Gough W. B., Zeiler R. H., Mehra R. Triggered ventricular rhythms in 1-day-old myocardial infarction in the dog. Circ Res. 1983 May;52(5):566–579. doi: 10.1161/01.res.52.5.566. [DOI] [PubMed] [Google Scholar]
  13. El-Sherif N., Hope R. R., Scherlag B. J., Lazzara R. Re-entrant ventricular arrhythmias in the late myocardial infarction period. 2. Patterns of initiation and termination of re-entry. Circulation. 1977 May;55(5):702–719. doi: 10.1161/01.cir.55.5.702. [DOI] [PubMed] [Google Scholar]
  14. 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 the "slow channel". Circulation. 1979 Sep;60(3):605–615. doi: 10.1161/01.cir.60.3.605. [DOI] [PubMed] [Google Scholar]
  15. Feldman R. D., Park G. D., Lai C. Y. The interaction of verapamil and norverapamil with beta-adrenergic receptors. Circulation. 1985 Sep;72(3):547–554. doi: 10.1161/01.cir.72.3.547. [DOI] [PubMed] [Google Scholar]
  16. Gibson D., Sowton E. The use of beta-adrenergic receptor blocking drugs in dysrhythmias. Prog Cardiovasc Dis. 1969 Jul;12(1):16–39. doi: 10.1016/0033-0620(69)90033-4. [DOI] [PubMed] [Google Scholar]
  17. Gilmour R. F., Jr, Heger J. J., Prystowsky E. N., Zipes D. P. Cellular electrophysiologic abnormalities of diseased human ventricular myocardium. Am J Cardiol. 1983 Jan 1;51(1):137–144. doi: 10.1016/s0002-9149(83)80024-1. [DOI] [PubMed] [Google Scholar]
  18. Goldstein D. S., Feuerstein G., Izzo J. L., Jr, Kopin I. J., Keiser H. R. Validity and reliability of liquid chromatography with electrochemical detection for measuring plasma levels of norepinephrine and epinephrine in man. Life Sci. 1981 Feb 2;28(5):467–475. doi: 10.1016/0024-3205(81)90139-9. [DOI] [PubMed] [Google Scholar]
  19. HAN J., GARCIADEJALON P., MOE G. K. ADRENERGIC EFFECTS ON VENTRICULAR VULNERABILITY. Circ Res. 1964 Jun;14:516–524. doi: 10.1161/01.res.14.6.516. [DOI] [PubMed] [Google Scholar]
  20. Hoffman B. F., Rosen M. R. Cellular mechanisms for cardiac arrhythmias. Circ Res. 1981 Jul;49(1):1–15. doi: 10.1161/01.res.49.1.1. [DOI] [PubMed] [Google Scholar]
  21. Hordof A. J., Spotnitz A., Mary-Rabine L., Edie R. N., Rosen M. R. The cellular electrophysiologic effects of digitalis on human atrial fibers. Circulation. 1978 Feb;57(2):223–229. doi: 10.1161/01.cir.57.2.223. [DOI] [PubMed] [Google Scholar]
  22. Hume J., Katzung B. G. Physiological role of endogenous amines in the modulation of ventricular automaticity in the guinea-pig. J Physiol. 1980 Dec;309:275–286. doi: 10.1113/jphysiol.1980.sp013508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jose A. D., Taylor R. R. Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. J Clin Invest. 1969 Nov;48(11):2019–2031. doi: 10.1172/JCI106167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kameyama M., Hofmann F., Trautwein W. On the mechanism of beta-adrenergic regulation of the Ca channel in the guinea-pig heart. Pflugers Arch. 1985 Oct;405(3):285–293. doi: 10.1007/BF00582573. [DOI] [PubMed] [Google Scholar]
  25. Kass R. S., Tsien R. W., Weingart R. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:209–226. doi: 10.1113/jphysiol.1978.sp012417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Katzung B. G., Morgenstern J. A. Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ Res. 1977 Jan;40(1):105–111. doi: 10.1161/01.res.40.1.105. [DOI] [PubMed] [Google Scholar]
  27. Klein G. J., Millman P. J., Yee R. Recurrent ventricular tachycardia responsive to verapamil. Pacing Clin Electrophysiol. 1984 Nov;7(6 Pt 1):938–948. doi: 10.1111/j.1540-8159.1984.tb05641.x. [DOI] [PubMed] [Google Scholar]
  28. Lerman B. B., Belardinelli L., West G. A., Berne R. M., DiMarco J. P. Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity. Circulation. 1986 Aug;74(2):270–280. doi: 10.1161/01.cir.74.2.270. [DOI] [PubMed] [Google Scholar]
  29. Lin F. C., Finley C. D., Rahimtoola S. H., Wu D. Idiopathic paroxysmal ventricular tachycardia with a QRS pattern of right bundle branch block and left axis deviation: a unique clinical entity with specific properties. Am J Cardiol. 1983 Jul;52(1):95–100. doi: 10.1016/0002-9149(83)90077-2. [DOI] [PubMed] [Google Scholar]
  30. Mary-Rabine L., Hordof A. J., Danilo P., Jr, Malm J. R., Rosen M. R. Mechanisms for impulse initiation in isolated human atrial fibers. Circ Res. 1980 Aug;47(2):267–277. doi: 10.1161/01.res.47.2.267. [DOI] [PubMed] [Google Scholar]
  31. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nguyen N. X., Yang P. T., Huycke E., Sung R. J. Verapamil and ventricular tachyarrhythmias. Pacing Clin Electrophysiol. 1987 May;10(3 Pt 1):571–578. doi: 10.1111/j.1540-8159.1987.tb04522.x. [DOI] [PubMed] [Google Scholar]
  33. Okumura K., Olshansky B., Henthorn R. W., Epstein A. E., Plumb V. J., Waldo A. L. Demonstration of the presence of slow conduction during sustained ventricular tachycardia in man: use of transient entrainment of the tachycardia. Circulation. 1987 Feb;75(2):369–378. doi: 10.1161/01.cir.75.2.369. [DOI] [PubMed] [Google Scholar]
  34. Palileo E. V., Ashley W. W., Swiryn S., Bauernfeind R. A., Strasberg B., Petropoulos A. T., Rosen K. M. Exercise provocable right ventricular outflow tract tachycardia. Am Heart J. 1982 Aug;104(2 Pt 1):185–193. doi: 10.1016/0002-8703(82)90190-9. [DOI] [PubMed] [Google Scholar]
  35. Reddy C. P., Gettes L. S. Use of isoproterenol as an aid to electric induction of chronic recurrent ventricular tachycardia. Am J Cardiol. 1979 Oct;44(4):705–713. doi: 10.1016/0002-9149(79)90291-1. [DOI] [PubMed] [Google Scholar]
  36. Reuter H., Scholz H. The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977 Jan;264(1):49–62. doi: 10.1113/jphysiol.1977.sp011657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Robertson D., Johnson G. A., Robertson R. M., Nies A. S., Shand D. G., Oates J. A. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation. 1979 Apr;59(4):637–643. doi: 10.1161/01.cir.59.4.637. [DOI] [PubMed] [Google Scholar]
  38. Rosen M. R., Danilo P., Jr Effects of tetrodotoxin, lidocaine, verapamil, and AHR-2666 on Ouabain-induced delayed afterdepolarizations in canine Purkinje fibers. Circ Res. 1980 Jan;46(1):117–124. doi: 10.1161/01.res.46.1.117. [DOI] [PubMed] [Google Scholar]
  39. Rosen M. R., Gelband H., Hoffman B. F. Correlation between effects of ouabain on the canine electrocardiogram and transmembrane potentials of isolated Purkinje fibers. Circulation. 1973 Jan;47(1):65–72. doi: 10.1161/01.cir.47.1.65. [DOI] [PubMed] [Google Scholar]
  40. Rosen M. R., Reder R. F. Does triggered activity have a role in the genesis of cardiac arrhythmias? Ann Intern Med. 1981 Jun;94(6):794–801. doi: 10.7326/0003-4819-94-6-794. [DOI] [PubMed] [Google Scholar]
  41. Rydén L., Ariniego R., Arnman K., Herlitz J., Hjalmarson A., Holmberg S., Reyes C., Smedgård P., Svedberg K., Vedin A. A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias. N Engl J Med. 1983 Mar 17;308(11):614–618. doi: 10.1056/NEJM198303173081102. [DOI] [PubMed] [Google Scholar]
  42. Scherlag B. J., Lau S. H., Helfant R. H., Berkowitz W. D., Stein E., Damato A. N. Catheter technique for recording His bundle activity in man. Circulation. 1969 Jan;39(1):13–18. doi: 10.1161/01.cir.39.1.13. [DOI] [PubMed] [Google Scholar]
  43. Schwartz A., Triggle D. J. Cellular action of calcium channel blocking drugs. Annu Rev Med. 1984;35:325–339. doi: 10.1146/annurev.me.35.020184.001545. [DOI] [PubMed] [Google Scholar]
  44. Schwartz P. J. The idiopathic long Q-T syndrome. Ann Intern Med. 1983 Oct;99(4):561–562. doi: 10.7326/0003-4819-99-4-561. [DOI] [PubMed] [Google Scholar]
  45. Spear J. F., Horowitz L. N., Hodess A. B., MacVaugh H., 3rd, Moore E. N. Cellular electrophysiology of human myocardial infarction. 1. Abnormalities of cellular activation. Circulation. 1979 Feb;59(2):247–256. doi: 10.1161/01.cir.59.2.247. [DOI] [PubMed] [Google Scholar]
  46. Stewart R. B., Bardy G. H., Greene H. L. Wide complex tachycardia: misdiagnosis and outcome after emergent therapy. Ann Intern Med. 1986 Jun;104(6):766–771. doi: 10.7326/0003-4819-104-6-766. [DOI] [PubMed] [Google Scholar]
  47. Strain J. E., Grose R. M., Factor S. M., Fisher J. D. Results of endomyocardial biopsy in patients with spontaneous ventricular tachycardia but without apparent structural heart disease. Circulation. 1983 Dec;68(6):1171–1181. doi: 10.1161/01.cir.68.6.1171. [DOI] [PubMed] [Google Scholar]
  48. Sung R. J., Shapiro W. A., Shen E. N., Morady F., Davis J. Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity. J Clin Invest. 1983 Jul;72(1):350–360. doi: 10.1172/JCI110975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sung R. J., Shen E. N., Morady F., Scheinman M. M., Hess D., Botvinick E. H. Electrophysiologic mechanism of exercise-induced sustained ventricular tachycardia. Am J Cardiol. 1983 Feb;51(3):525–530. doi: 10.1016/s0002-9149(83)80092-7. [DOI] [PubMed] [Google Scholar]
  50. TAYLOR R. R., JOHNSTON C. I., JOSE A. D. REVERSAL OF DIGITALIS INTOXICATION BY BETA-ADRENERGIC BLOCKADE WITH PRONETHALOL. N Engl J Med. 1964 Oct 22;271:877–882. doi: 10.1056/NEJM196410222711704. [DOI] [PubMed] [Google Scholar]
  51. Tsien R. W., Carpenter D. O. Ionic mechanisms of pacemaker activity in cardiac Purkinje fibers. Fed Proc. 1978 Jun;37(8):2127–2131. [PubMed] [Google Scholar]
  52. Vargas G., Akhtar M., Damato A. N. Electrophysiologic effects of isoproterenol on cardiac conduction system in man. Am Heart J. 1975 Jul;90(1):25–34. doi: 10.1016/0002-8703(75)90253-7. [DOI] [PubMed] [Google Scholar]
  53. Vassalle M. The relationship among cardiac pacemakers. Overdrive suppression. Circ Res. 1977 Sep;41(3):269–277. doi: 10.1161/01.res.41.3.269. [DOI] [PubMed] [Google Scholar]
  54. Vignola P. A., Aonuma K., Swaye P. S., Rozanski J. J., Blankstein R. L., Benson J., Gosselin A. J., Lister J. W. Lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immunosuppression. J Am Coll Cardiol. 1984 Oct;4(4):812–819. doi: 10.1016/s0735-1097(84)80411-8. [DOI] [PubMed] [Google Scholar]
  55. Wellens H. J., Bär F. W., Lie K. I., Düren D. R., Dohmen H. J. Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardiol. 1977 Oct;40(4):579–585. doi: 10.1016/0002-9149(77)90074-1. [DOI] [PubMed] [Google Scholar]
  56. Wellens H. J. Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation. 1978 May;57(5):845–853. doi: 10.1161/01.cir.57.5.845. [DOI] [PubMed] [Google Scholar]
  57. Wit A. L., Allessie M. A., Bonke F. I., Lammers W., Smeets J., Fenoglio J. J., Jr Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses. Experimental approach and initial results demonstrating reentrant excitation. Am J Cardiol. 1982 Jan;49(1):166–185. doi: 10.1016/0002-9149(82)90292-2. [DOI] [PubMed] [Google Scholar]
  58. Wit A. L., Cranefield P. F., Gadsby D. C. Electrogenic sodium extrusion can stop triggered activity in the canine coronary sinus. Circ Res. 1981 Oct;49(4):1029–1042. doi: 10.1161/01.res.49.4.1029. [DOI] [PubMed] [Google Scholar]
  59. Wit A. L., Cranefield P. F. Triggered activity in cardiac muscle fibers of the simian mitral valve. Circ Res. 1976 Feb;38(2):85–98. doi: 10.1161/01.res.38.2.85. [DOI] [PubMed] [Google Scholar]
  60. Wit A. L., Cranefield P. F. Triggered and automatic activity in the canine coronary sinus. Circ Res. 1977 Oct;41(4):434–445. doi: 10.1161/01.res.41.4.434. [DOI] [PubMed] [Google Scholar]
  61. Woelfel A., Foster J. R., McAllister R. G., Jr, Simpson R. J., Jr, Gettes L. S. Efficacy of verapamil in exercise-induced ventricular tachycardia. Am J Cardiol. 1985 Aug 1;56(4):292–297. doi: 10.1016/0002-9149(85)90852-5. [DOI] [PubMed] [Google Scholar]
  62. Woelfel A., Foster J. R., Simpson R. J., Jr, Gettes L. S. Reproducibility and treatment of exercise-induced ventricular tachycardia. Am J Cardiol. 1984 Mar 1;53(6):751–756. doi: 10.1016/0002-9149(84)90398-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES