Skip to main content
Heart logoLink to Heart
. 1996 Mar;75(3):281–286. doi: 10.1136/hrt.75.3.281

Discrepant effects of mexiletine on cycle length of ventricular tachycardia and on the effective refractory period in the area of slow conduction.

Y Aizawa 1, M Chinushi 1, H Kitazawa 1, T Washizuka 1, A Abe 1, A Shibata 1, I Kodama 1
PMCID: PMC484287  PMID: 8800993

Abstract

OBJECTIVE: Monomorphic sustained ventricular tachycardia (VT) can often be entrained and interrupted at a critical paced cycle length. The aim was to evaluate a possible determinant of this phenomenon by observing the action of mexiletine on the critical paced cycle length and other variables. METHODS: Nine consecutive patients with symptomatic VT were studied. After induction of VT, the area of slow conduction was mapped as the earliest site of the activation or the site with mid-diastolic potential during the tachycardia. Rapid pacing was performed at a site distant from the tachycardia circuit to entrain the tachycardia, starting at a cycle length 10-20 ms shorter than the VT cycle length, and repeated after a decrement of the cycle length in steps of 10 ms to obtain the longest paced cycle length that interrupted the tachycardia: the block cycle length. The effective refractory period (ERP) was measured at the pacing site at which the myocardium was presumed to be normal and also in the area of slow conduction. The effects of mexiletine on the cycle length of VT, the block cycle length, and the ERP at two sites were obtained before and after mexiletine administration. The relation between the cycle length of VT and block cycle length and their changes were also analysed. RESULTS: 11 VTs with the same morphology were induced before and after mexiletine administration. The VT cycle length was prolonged by mexiletine from 309 (SD 53) to 361 (47) ms, and it was interrupted at block cycle lengths of 247 (37) and 307 (41) ms, respectively, the changes being 18 (12)% and 23 (8)% (both P < 0.001). All VTs were entrained, and during pacing at the block cycle length there was abrupt loss of fusion and change in the presystolic electrogram, always associated with interruption of VT on cessation of rapid pacing. A good correlation was observed between the VT cycle length and the block cycle length (r = 0.77 to 0.80). The ERP at the pacing site (normal myocardium) and in the area of slow conduction showed no significant change: 241 (21) v 240 (22) ms and 262 (9) v 252 (9) ms, respectively. The block cycle length was longer than the ERP after mexiletine administration: 362 (55) v 252 (9) ms (P < 0.02). CONCLUSIONS: Mexiletine prolonged the cycle length of VT and the VT-interrupting critical cycle length but not the ERP. The prolongation of the VT cycle length and the block cycle length by mexiletine seemed to be unrelated to the action potential duration, but related to depressed intercellular conduction.

Full text

PDF
281

Selected References

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

  1. Aizawa Y., Naitoh N., Kitazawa H., Kusano Y., Uchiyama H., Washizuka T., Shibata A. Frequency of presumed reentry with an excitable gap in sustained ventricular tachycardia unassociated with coronary artery disease. Am J Cardiol. 1993 Oct 15;72(12):916–921. doi: 10.1016/0002-9149(93)91107-s. [DOI] [PubMed] [Google Scholar]
  2. Aizawa Y., Naitoh N., Washizuka T., Kitazawa H., Takahashi K., Kodama I., Shibata A. Procainamide-induced changes in reentrant ventricular tachycardia with special reference to the tachycardia-interrupting critical paced cycle length during transient entrainment with rapid pacing. Jpn Heart J. 1994 Sep;35(5):611–623. doi: 10.1536/ihj.35.611. [DOI] [PubMed] [Google Scholar]
  3. Aizawa Y., Niwano S., Chinushi M., Tamura M., Kusano Y., Miyajima T., Kitazawa H., Shibata A. Incidence and mechanism of interruption of reentrant ventricular tachycardia with rapid ventricular pacing. Circulation. 1992 Feb;85(2):589–595. doi: 10.1161/01.cir.85.2.589. [DOI] [PubMed] [Google Scholar]
  4. Brugada J., Boersma L., Abdollah H., Kirchhof C., Allessie M. Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions. Circulation. 1992 May;85(5):1879–1887. doi: 10.1161/01.cir.85.5.1879. [DOI] [PubMed] [Google Scholar]
  5. Campbell T. J. Kinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983 Jun;17(6):344–352. doi: 10.1093/cvr/17.6.344. [DOI] [PubMed] [Google Scholar]
  6. El-Sherif N., Mehra R., Gough W. B., Zeiler R. H. Reentrant ventricular arrhythmias in the late myocardial infarction period. Interruption of reentrant circuits by cryothermal techniques. Circulation. 1983 Sep;68(3):644–656. doi: 10.1161/01.cir.68.3.644. [DOI] [PubMed] [Google Scholar]
  7. Fontaine G., Frank R., Tonet J., Grosgogeat Y. Identification of a zone of slow conduction appropriate for VT ablation: theoretical and practical considerations. Pacing Clin Electrophysiol. 1989 Jan;12(1 Pt 2):262–267. doi: 10.1111/j.1540-8159.1989.tb02656.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Grant A. O., Starmer C. F., Strauss H. C. Antiarrhythmic drug action. Blockade of the inward sodium current. Circ Res. 1984 Oct;55(4):427–439. doi: 10.1161/01.res.55.4.427. [DOI] [PubMed] [Google Scholar]
  10. Hondeghem L. M., Katzung B. G. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. Annu Rev Pharmacol Toxicol. 1984;24:387–423. doi: 10.1146/annurev.pa.24.040184.002131. [DOI] [PubMed] [Google Scholar]
  11. Josephson M. E., Horowitz L. N., Spielman S. R., Waxman H. L., Greenspan A. M. Role of catheter mapping in the preoperative evaluation of ventricular tachycardia. Am J Cardiol. 1982 Jan;49(1):207–220. doi: 10.1016/0002-9149(82)90295-8. [DOI] [PubMed] [Google Scholar]
  12. Kay G. N., Epstein A. E., Plumb V. J. Incidence of reentry with an excitable gap in ventricular tachycardia: a prospective evaluation utilizing transient entrainment. J Am Coll Cardiol. 1988 Mar;11(3):530–538. doi: 10.1016/0735-1097(88)91527-6. [DOI] [PubMed] [Google Scholar]
  13. Kay G. N., Epstein A. E., Plumb V. J. Preferential effect of procainamide on the reentrant circuit of ventricular tachycardia. J Am Coll Cardiol. 1989 Aug;14(2):382–390. doi: 10.1016/0735-1097(89)90190-3. [DOI] [PubMed] [Google Scholar]
  14. Kodama I., Wilde A., Janse M. J., Durrer D., Yamada K. Combined effects of hypoxia, hyperkalemia and acidosis on membrane action potential and excitability of guinea-pig ventricular muscle. J Mol Cell Cardiol. 1984 Mar;16(3):247–259. doi: 10.1016/s0022-2828(84)80591-x. [DOI] [PubMed] [Google Scholar]
  15. Morady F., Frank R., Kou W. H., Tonet J. L., Nelson S. D., Kounde S., De Buitleir M., Fontaine G. Identification and catheter ablation of a zone of slow conduction in the reentrant circuit of ventricular tachycardia in humans. J Am Coll Cardiol. 1988 Apr;11(4):775–782. doi: 10.1016/0735-1097(88)90211-2. [DOI] [PubMed] [Google Scholar]
  16. Okumura K., Henthorn R. W., Epstein A. E., Plumb V. J., Waldo A. L. Further observations on transient entrainment: importance of pacing site and properties of the components of the reentry circuit. Circulation. 1985 Dec;72(6):1293–1307. doi: 10.1161/01.cir.72.6.1293. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Szekeres L., Williams E. M. Antifibrillatory action. J Physiol. 1962 Mar;160(3):470–482. doi: 10.1113/jphysiol.1962.sp006860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. WILLIAMS E. M., SZEKERES L. A comparison of tests for antifibrillatory action. Br J Pharmacol Chemother. 1961 Dec;17:424–432. doi: 10.1111/j.1476-5381.1961.tb01129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Waldecker B., Coromilas J., Saltman A. E., Dillon S. M., Wit A. L. Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment. Circulation. 1993 Apr;87(4):1286–1305. doi: 10.1161/01.cir.87.4.1286. [DOI] [PubMed] [Google Scholar]
  21. Waldo A. L., Henthorn R. W., Plumb V. J., MacLean W. A. Demonstration of the mechanism of transient entrainment and interruption of ventricular tachycardia with rapid atrial pacing. J Am Coll Cardiol. 1984 Feb;3(2 Pt 1):422–430. doi: 10.1016/s0735-1097(84)80030-3. [DOI] [PubMed] [Google Scholar]
  22. de Bakker J. M., van Capelle F. J., Janse M. J., Wilde A. A., Coronel R., Becker A. E., Dingemans K. P., van Hemel N. M., Hauer R. N. Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. Circulation. 1988 Mar;77(3):589–606. doi: 10.1161/01.cir.77.3.589. [DOI] [PubMed] [Google Scholar]

Articles from Heart are provided here courtesy of BMJ Publishing Group

RESOURCES