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Lidocaine has a narrow antiarrhythmic dose range against ventricular arrhythmias induced by programmed electrical stimulation in conscious postinfarction dogs

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Summary

The aim of the present study was to investigate the dose-dependent antiarrhythmic efficacy of lidocaine against electrically induced tachycardias in conscious, chronically instrumented postinfarction dogs. Programmed electrical stimulation (PES) was performed in 16 dogs 8 to 21 days after a 4 h occlusion of the left anterior descending coronary artery (LAD). Infusion of saline in 8 control animals with sustained ventricular tachycardia (SVT) inducible at baseline did not affect subsequent inducibility. In the treatment group 7 of 8 animals responded with SVT and one exhibited ventricular fibrillation at baseline. After an initial bolus of 1 mg/kg lidocaine intravenously (i.v.), the drug was infused at infusion rates of 40, 80 and 120 μg/kg/min (i.v.). During 80 μg/kg/min lidocaine (mean plasma level 3.5 μg/ml) 7 out of 8 animals displayed an antiarrhythmic response; both the lower and the higher infusion rate were associated with a smaller antiarrhythmic efficacy (3 of 8 animals responded to 40 μg/kg/min and 4 of 8 to 120 μg/kg/min). Licocaine did not affect ventricular refractory periods, but induced an increase in intraventricular conduction time at all infusion rates, from 66.2 ms at baseline to 67.7 ms (p<0.05), 67.7 ms (p<0.05), 70.0 ms (p<0.01) respectively.

In conclusion the present study demonstrates that lidocaine is of considerable value in the management of PES-induced ventricular arrhythmias in the postinfarction phase. However there is only a small optimal therapeutic plasma level range, where lidocaine exhibits its antiarrhythmic efficacy against this type of arrhythmia; this makes a carefully titration of the drug necessary both in the experimental and in the clinical setting.

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References

  • Alderman EL, Kerber RD, Harrison DC (1974) Evaluation of lidocaine resistance in man using intermittent high-dose infusion techniques. Am J Cardiol 34:342–349

    Google Scholar 

  • Anderson JL (1984) Current understanding of lidocaine as an antiarrhythmic agent: a review. Clin Ther 6:125–141

    Google Scholar 

  • Anderson KP, Walker R, Lux RL, Ershler PR, Menlove R, Williams MR, Krall R, Moddrelle D (1990) Conduction velocity depression and drug-induced ventricular tachyarrhythmias. Effects of lidocaine on the intact canine heart. Circulation 81:1024–1038

    Google Scholar 

  • Brodsky MA, Allen BJ, Luckett CR, Capparelli EV, Wolff LJ, Henry WL (1989) Antiarrhythmic efficacy of solitary beta-adrenergic blockade for patients with sustained ventricular tachyarrhythmias. Am Heart J 118:272–280

    Google Scholar 

  • Collinsworth KA, Kalman SM, Harrison DC (1974) The clinical pharmacology of lidocaine as an antiarrhyhthmic drug. Circulation 50:1217–1230

    Google Scholar 

  • Davis J, Glassman R, Wit AL (1972) Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted heart. Am J Cardiol 49:1176–1184

    Google Scholar 

  • Duff HJ, Mitchell LB, Wyse DG (1985) Mexiletine-quinidine: Frequency-dependent changes in ventricular refractoriness associated with antiarrhythmic efficacy. Circulation 72 [Suppl III]:111–164

    Google Scholar 

  • Furukawa T, Rozanski JJ, Moroe K, Gosselin AJ, Listere JW (1989) Efficacy of procainamide on ventricular tachycardia: Relation to prolongation of refractoriness and slowing of conduction. Circulation 118:702–708

    Google Scholar 

  • Gerstenblith G, Spear JF, Moore EN (1972) Quantitative study of the effect of lidocaine on the threshold for ventricular fibrillation in the dog. Am J Cardiol 30:242–247

    Google Scholar 

  • Gianelly R, Groeben JO, Spivack AP, Harrison DC (1967) Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. N Engl J Med 277:1215–1219

    Google Scholar 

  • Hunt GB, Ross DL (1989) Influence of infarct age on reproducibility of ventricular tachycardia induction in a canine model. J Am Coll Cardiol 14:765–773

    Google Scholar 

  • Iesaka Y, Aonuma K, Nitta J, Tokunaga T, Fujiwara H, Hiraoka M (1988) Effects of procainamide and lidocaine on electrically inducible ventricular tachycardia studied with programmed ventricular stimulation in post myocardial infarction. Jpn Circ J 52:262–271

    Google Scholar 

  • Janse MJ, Wit AL (1989) Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69:1049–1169

    Google Scholar 

  • Karagueuzian HS, Fenoglio JJ, Weiss MB, Wit AL (1979) Protracted ventricular tachycardia induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion. Circ Res 44:833–846

    Google Scholar 

  • Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989a) Holter monitoring in conscious dogs: assessment of arrhythmias occurring during ischemia and in the early reperfusion phase. J Pharmacol Methods 22:77–91

    Google Scholar 

  • Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989b) Holter monitoring in conscious dogs: assessment of arrhythmias occurring in the late reperfusion phase after coronary occlusion. J Pharmacol Methods 22:93–102

    Google Scholar 

  • Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1990) Programmed electrical stimulation after myocardial infarction and reperfusion in conscious dogs. J Pharmacol Methods 23:155–169

    Google Scholar 

  • Lynch JJ, Heaney LA, Wallace AA, Gehret JR, Stein RB (1990) Failure of lidocaine to suppress lethal ischemic ventricular arrhythmias in a canine model of previous myocardial infarction. J Cardiovasc Pharmacol 16:41–49

    Google Scholar 

  • Miyazaki T, Ogawa S, Sakai T, Hosokawa M, Sakurai K, Nakamura Y (1988) Effects of class I drugs on reentrant ventricular tachycardia in a canine model of myocardial infarction: On their antiarrhythmic and proarrhythmic mechanisms. Jpn Circ J 52:254–261

    Google Scholar 

  • Patterson E, Gibson JK, Lucchesi BR (1982) Electrophysiologic actions of lidocaine in a canine model of chronic myocardial ischemic damage — Arrhythmogenic actions of lidocaine. J Cardiovasc Pharmacol 4:925–934

    Google Scholar 

  • Patterson E, Gibson JK, Lucchesi BR (1988) Antiarrhythmic and arrhythmogenic actions of methyl lidocaine during the recovery phase after canine myocardial infarction. Pharmacology 36:73–83

    Google Scholar 

  • Reiter MJ, Easley AR, Mann DE (1987) Efficacy of class Ib (lidocainelike) antiarrhythmic agents for prevention of sustained ventricular tachycardia secondary to coronary artery disease. Am J Cardiol 59:1319–1324

    Google Scholar 

  • Schmitt C, Brachmann J, Waldecker B, Rizos I, Senges J, Kübler W (1987) Amiodarone in patients with recurrent sustained ventricular tachyarrhythmias: results of programmed electrical stimulation and long-term clinical outcome in chronic treatment. Am Heart J 114:279–283

    Google Scholar 

  • Smeets JLRM, Allessie MA, Lammers WJEP, Bonke FIM, Hollen J (1986) The wavelength of the cardiac impulse and reentrant arrhythmias in isolated rabbit atrium. Circ Res 58:96–108

    Google Scholar 

  • Todt H, Krumpl G, Krejcy K, Raberger G (1991) Comparison of the antiarrhythmic effects of dl-sotalol and d-sotalol in a conscious canine model of recent myocardial infarction. Z Kardiol 80 [Suppl 3]:41

    Google Scholar 

  • Todt H, Krumpl G, Krejcy K, Raberger G (1992) Mode of QT correction for heart rate: implications for the detection of inhomogeneous repolarisation following myocardial infarction. Am Heart J (in press)

  • Van de Water A, Verheyen J, Xhonneux R, Reneman RS (1989) An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. J Pharmacol Methods 22:207–217

    Google Scholar 

  • Wilber DJ, Lynch JJ, Montgomery D, Lucchesi BR (1985) Postinfarction sudden death: significance of inducible ventricular tachycardia and infarct size in a conscious canine model. Am Heart J 109:8–18

    Google Scholar 

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Krejcy, K., Krumpl, G., Todt, H. et al. Lidocaine has a narrow antiarrhythmic dose range against ventricular arrhythmias induced by programmed electrical stimulation in conscious postinfarction dogs. Naunyn-Schmiedeberg's Arch Pharmacol 346, 213–218 (1992). https://doi.org/10.1007/BF00165304

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  • DOI: https://doi.org/10.1007/BF00165304

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