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. 1983 May;71(5):1247–1253. doi: 10.1172/JCI110874

Inhibition of cardiac sympathetic nerve activity during intravenous administration of lidocaine.

B D Miller, M D Thames, A L Mark
PMCID: PMC436985  PMID: 6853712

Abstract

The antiarrhythmic action of lidocaine has been attributed solely to its direct electrophysiological effects on the heart. However, lidocaine is particularly effective in treating ventricular arrhythmias associated with increased sympathetic activity, e.g., in myocardial infarction and digitalis toxicity. We tested the hypothesis that lidocaine administered intravenously depressed cardiac sympathetic nerve activity (CSNA). We measured CSNA in six dogs in control state and after lidocaine in doses of 0.625, 1.25, and 2.5 mg/kg i.v. over 2 min. These doses of lidocaine produced graded decreases of CSNA of -8 +/- 2, -18 +/- 1, and -41 +/- 5%, respectively (P less than 0.05, mean +/- SE). In six additional experiments the bolus of lidocaine was followed by an infusion for 20 min (1.25 mg/kg followed by 100 micrograms/kg per min and 2.5 mg/kg followed by 200 micrograms/kg per min). Infusion of lidocaine maintained depression of CSNA at a level that was 23 +/- 3 and 35 +/- 5% less than control (P less than 0.05), respectively, at plasma lidocaine levels of 5.2 +/- 0.6 and 7.5 +/- 1.4 micrograms/ml, respectively. CSNA returned to control during recovery periods. CSNA did not decrease with the passage of time or administration of vehicle. In five dogs with vagi intact, carotid sinuses isolated and held at a pressure of 100 mmHg, and aortic baroreceptors denervated, administration of lidocaine (2.5 mg/kg followed by 200 micrograms/kg per min) decreased renal nerve activity to 71 +/- 8% of control. Increases in left ventricular systolic pressure and maximum derivative of pressure with respect to time (dP/dtmax) resulting from electrical stimulation of preganglionic sympathetic nerves were not significantly altered by lidocaine, but were markedly attenuated by hexamethonium, a ganglionic blocker. In conclusion, lidocaine administered intravenously produces dose-dependent and sustained decreases in cardiac sympathetic nerve activity. These decreases can occur with therapeutic plasma levels. We speculate that this effect is due to central nervous system effects of the drug and that this effect may contribute to the antiarrhythmic actions of lidocaine.

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Selected References

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

  1. Austen W. G., Moran J. M. Cardiac and peripheral vascular effects of lidocaine and procainamide. Am J Cardiol. 1965 Nov;16(5):701–707. doi: 10.1016/0002-9149(65)90054-8. [DOI] [PubMed] [Google Scholar]
  2. Boyajy L. D., Nash C. B. Alteration of ouabain taxicity by cardiac denervation. Toxicol Appl Pharmacol. 1966 Sep;9(2):199–208. doi: 10.1016/0041-008x(66)90114-1. [DOI] [PubMed] [Google Scholar]
  3. ERLIJ D., MENDEZ R. THE MODIFICATION OF DIGITALIS INTOXICATION BY EXCLUDING ADRENERGIC INFLUENCES ON THE HEART. J Pharmacol Exp Ther. 1964 Apr;144:97–103. [PubMed] [Google Scholar]
  4. Evans D. E., Gillis R. A. Effect of diphenylhydantoin and lidocaine on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther. 1974 Dec;191(3):506–517. [PubMed] [Google Scholar]
  5. Felder R. B., Thames M. D. Responses to activation of cardiac sympathetic afferents with epicardial bradykinin. Am J Physiol. 1982 Feb;242(2):H148–H153. doi: 10.1152/ajpheart.1982.242.2.H148. [DOI] [PubMed] [Google Scholar]
  6. Felder R. B., Thames M. D. The cardiocardiac sympathetic reflex during coronary occlusion in anesthetized dogs. Circ Res. 1981 May;48(5):685–692. doi: 10.1161/01.res.48.5.685. [DOI] [PubMed] [Google Scholar]
  7. Ferrario C. M., Gildenberg P. L., McCubbin J. W. Cardiovascular effects of angiotensin mediated by the central nervous system. Circ Res. 1972 Mar;30(3):257–262. doi: 10.1161/01.res.30.3.257. [DOI] [PubMed] [Google Scholar]
  8. Gillis R. A., Levine F. H., Thibodeaux H., Raines A., Standaert F. G. Comparison of methyllidocaine and lidocaine on arrhythmias produced by coronary occlusion in the dog. Circulation. 1973 Apr;47(4):697–703. doi: 10.1161/01.cir.47.4.697. [DOI] [PubMed] [Google Scholar]
  9. Gillis R. A., Raines A., Sohn Y. J., Levitt B., Standaert F. G. Neuroexcitatory effects of digitalis and their role in the development of cardiac arrhythmias. J Pharmacol Exp Ther. 1972 Oct;183(1):154–168. [PubMed] [Google Scholar]
  10. Hilmi K. I., Regan T. J. Relative effectiveness of antiarrhythmic drugs in treatment of digitalis-induced ventricular tachycardia. Am Heart J. 1968 Sep;76(3):365–369. doi: 10.1016/0002-8703(68)90232-9. [DOI] [PubMed] [Google Scholar]
  11. Malliani A., Schwartz P. J., Zanchetti A. A sympathetic reflex elicited by experimental coronary occlusion. Am J Physiol. 1969 Sep;217(3):703–709. doi: 10.1152/ajplegacy.1969.217.3.703. [DOI] [PubMed] [Google Scholar]
  12. Paradise R. R. Antiarrhythmic activity of lidocaine and N-isopropyl-p-nitrophenylethanolamine (INPEA) in acetyl strophanthidin-induced arrhythmias. Arch Int Pharmacodyn Ther. 1967 Oct;169(2):482–493. [PubMed] [Google Scholar]
  13. Spector R. Transport of lignocaine by rabbit choroid plexus in vitro. Clin Sci (Lond) 1980 Jan;58(1):107–109. doi: 10.1042/cs0580107. [DOI] [PubMed] [Google Scholar]
  14. Thorén P., Oberg B. Studies on the endoanesthetic effects of lidocaine and benzonatate on non-medullated nerve endings in the left ventricle. Acta Physiol Scand. 1981 Jan;111(1):51–58. doi: 10.1111/j.1748-1716.1981.tb06704.x. [DOI] [PubMed] [Google Scholar]
  15. Usubiaga J. E., Moya F., Wikinski J. A., Wikinski R., Usubiaga L. E. Relationship between the passage of local anaesthetics across the blood-brain barrier and their effects on the central nervous system. Br J Anaesth. 1967 Dec;39(12):943–947. doi: 10.1093/bja/39.12.943. [DOI] [PubMed] [Google Scholar]
  16. WEISS W. A. Intravenous use of lidocaine for ventricular arrhythmias. Anesth Analg. 1960 Jul-Aug;39:369–381. [PubMed] [Google Scholar]
  17. Webb S. W., Adgey A. A., Pantridge J. F. Autonomic disturbance at onset of acute myocardial infarction. Br Med J. 1972 Jul 8;3(5818):89–92. doi: 10.1136/bmj.3.5818.89. [DOI] [PMC free article] [PubMed] [Google Scholar]

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