Abstract
Lidocaine, a local anaesthetic, has been shown to reduce ventricular arrhythmias associated with myocardial infarction and ischemic myocardial injury and its protective effects has been attributed to its membrane stabilizing properties. Since oxygen radicals are known to be produced during ischemia induced tissue damage, we have investigated the possible antioxidant properties of lidocaine and found that lidocaine does not scavenge 02 −· radicals at 1 to 20 mM concentrations. However, lidocaine was found to be a potent scavenger of hydroxyl radicals and singlet oxygen. Hydroxyl radicals were produced in a Fenton type reaction and detected as DMPO-OH adducts by electron paramagnetic resonance spectroscopic techniques. Lidocaine inhibited DMPO-OH adduct formation in a dose dependent manner. The amount of lidocaine needed to cause 50% inhibition of that rate was found to be approximately 80 μM and at 300 μM concentration it virtually eliminated the DMPO-OH adduct formation. The production of OH-dependent TBA reactive products of deoxyribose was also inhibited by lidocaine in a dose dependent manner. Lidocaine was also found to inhibit the 1O2-dependent 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) formation in a dose dependent manner. 1O2 was produced in a photosensitizing system using Rose Bengal or Methylene Blue as photosensitizers and was detected as TEMP-1O2 adduct by EPR spectroscopy. The amount of lidocaine required to cause 50% inhibition of TEMP-1O2 adduct formation was found to be 500 μM. These results suggest that the protective effect of lidocaine on myocardial injury may, in part, be due to its reactive oxygen scavenging properties. These results may also explain the ‘membrane stabilizing actions’ of lidocaine by scavenging OH · and 1O2 that are implicated in membrane lipid peroxidation.
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References
Harrison DC, Sprouse JH, Morrow AG: Antiarrhythmic properties of lidocaine and procainamide: Clinical and physiologic studies of their cardiovascular effects in man. Circulation 28: 486–491, 1963
Gianelly R, von der Groeben JO, Spivack AP, Harrison DC: Effects of lidocaine on ventricular arrhythmias in patients with coronary heart disease. New Engl J Med 277: 1215–1221, 1967
Jewitt DE, Kishon Y, Thomas M: Lignocaine in the management of arrhythmias after acute myocardial infraction. Lancet 2: 266–268, 1968
Pfeiffer CJ, Keith JC, Cho CH, DeRolf S, Pfeiffer DC, Misra HP: Gastric and cardiac protection by lidocaine. Acta Phys. Hung 73: 129–136, 1989
Nasser FN, Walls JT, Edwards WD, Harison CE Jr: Lidocaine-induced reduction in size of experimental myocardial infraction. Am J Cardiol 46: 967–975, 1980
Boudolulars H, Karayannacos PE, Lewis RP, Kakos GS, Kilman JW, Vasko JS: Potential effect of lidocaine on ischemic myocardial injury: Experimental and clinical observations. J Surg Res 24: 469–476, 1978
Narang KP, Crouthamel WG, Carliner HN, Fisher ML: Lidocaine and its active metabolites. Clin Pharmacol Ther 654–622, 1978
Guarnieri C, Flamigni F, Caldarera CM: Role of oxygen in the cellular damage induced by reoxygenation of hypoxic heart. J Mol Cell Cardiol 12: 797–808, 1980
Hess ML, Manson NH, Okabe E: Involvement of free radicals in the pathophysiology of ischemic heart disease. Can J Physiol Pharmacol 60: 1382–1389, 1982
McCord JM, Roy RS: The pathophysiology of superoxide: Roles in inflammation and ischemia. Can J Physiol Pharmacol 60: 1346–1352, 1982
Rao PS, Mueller HS: Lipid peroxidation and myocardial ischemia. In: JJ Spitzer (ed.) Myocardial Injury. Plenum Publishing Co., New York, 1983, pp 341–367
Fridovich I: Hypoxia and oxygen toxicity. Adv Neurol 26: 255–259, 1979
Misra HP, Weglicki WB, Abdula R, Mc Cay PB: Identification of a carbon-centered free radical during reperfusion injury in ischemic heart. Circulation 70: 11–260, 1984
Carmen MA, Kramer JH, Benjamin FD, Weglicki WB: Identification of free radicals in myocardial ischemia/reperfusion by spin trapping with nitrone DMPO. FEBS Lett 221: 101–104, 1987
Baron DW, Sunamori M, Harrison CE: Preservation of oxidative phosphorylation by lidocaine in ischemic and reperfused myocardium. Adv Myocardial 4: 567–573, 1983
She ZW, Liming JD, Fagan JB, Pacht ER, Davis WB: Inhibition of hypochlorous acid by lidocaine and native components of alveolar epithelial lining fluid. Am Rev Respir Dis 144: 227–230, 1991
Mak IT, Weglicki WB: Protection by B-Blocking agents against free radical-mediated sarcolemmal lipid peroxidation. Circ Res 63: 262–266, 1988
Kalyanaraman B: Detection of toxic free radicals in biology and medicine. In: E Hodgson, JR Bend, RM Philpot (eds.) Reviews in Biochemical Toxicology. Elsevier Biomedical, New York, pp 73–139
Schaub RG, Stewart G, Strong M, Ruofolo R, Lemole G: Reduction of ischemic myocardial damage in the dog by lidocaine infusion. Am J Pathol 87: 388–414, 1977
Stelzner TJ, Welsh CH, Berger E, McCullough RG, Morris K, Repine JE, Weil JV: Antiarrhythmic agents diminish thiourea induced pulmonary vascular protein leak in rats. J Appl Physiol 63: 1877–1883, 1987
Halliwell B, Gutteridge JMC: Formation of a thiobarbituric-acid-reactive substance from deoxyribose in the presence of iron salts. FEBS Lett 128: 347–351, 1981
McCord JM, Fridovich I: The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem 243: 5753–5760, 1968
Misra HP, Fridovich I: The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247: 3170–3175, 1972
Zang L, Zhang Z, Misra HP: EPR studies of trapped singlet oxygen (1O2) generated during photoirradiation of Hypocrellin A. Photochem Photobiol 52: 677–684, 1990
Misra BR, Misra HP: Vasoactive intestinal peptide, a singlet oxygen quencher. J Biol Chem 265: 15371–15374, 1990
Hearse JD, O'Brian OK, Braimbridge M: Protection of the myocardium during ischemic arrest. J Thorac Cardiovasc Surg 81: 873–879, 1981
Schaub RG, Lemole MG, Pinder GC, Black P: Effects of lidocaine and epinephrine on myocardial preservation following cardiopulmonary bypass in the dog. J Thorac Cardiovasc Surg 74: 571–576, 1977
Bernier M, Hearse JD, Manning AS: Reperfusion-induced arrhythmias and oxygen derived free radicals. Studies with anti-free radical interventions and a free radical generating system in the isolated perfused heart. Circ Res 58: 331–340, 1986
Shlafer M, Kane PF, Kirsh MM: Superoxide dismutase plus catalase enhances the efficacy of the hypothermic cardioplegia to protect globally ischemic, reperfused heart. J Thorac Cardiovasc Surg 83: 830–839, 1982
Woodward B, Zakaria M: Effects of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart. J Moll Cell Cardiol 16: 497–517, 1984
Manning AS, Coltart JD, Hearse DJ: Ischemia and reperfusion-induced arrhythmias in the rat. Circ Res 55: 545–550, 1984
Svingen AS, O'Neal FO, Aust SD: The role of superoxide and singlet oxygen in lipid peroxidation. Photochem Photobiol 28: 803–809, 1978
Niki E, Yamamoto Y, Kamiya Y: Inhibition of Peroxidations of liposomal and biomembranes by water soluble antioxidants. In: A Sevanian (ed.) Lipid Peroxidation in Biological Systems. American Oil Chemists Society, Champaign, Illinois, 1988, pp 32–50
Gauduel Y, Duvelleray MA: Oxygen radicals in cardiac injury due to reoxygenation. J Mol. Cell Cardiol 16: 458–470, 1984
Cohen G: The generation of hydroxyl radicals in biologic systems: Toxicological aspects. Photochem Photobiol 28: 669–675, 1978
Zweier JL, Flaherty JT, Weisfeldt ML: Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci 84: 1404–1407, 1987
Keith JC Jr: Effect of lidocaine pretreatment on acute haemorragic shock in the aneasthetized rat. Circ Shock 19: 283–292, 1986
Novelli GP: Free radicals and circulatory shock. In: L'Abbate A, Ursini F (eds.) The role of Oxygen Radicals in Cardiovascular Diseases. Kluwer Academic Publishers, Dordrecht, The Netherlands, 1986, pp 13–22.
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Das, K.C., Misra, H.P. Lidocaine: a hydroxyl radical scavenger and singlet oxygen quencher. Mol Cell Biochem 115, 179–185 (1992). https://doi.org/10.1007/BF00230329
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DOI: https://doi.org/10.1007/BF00230329