Modulation of the electrical restitution of canine Purkinje fibers by local anesthetic drugs: a study with flecainide and propafenone.
Some antiarrhythmic drugs that depress conduction also influence action potential duration (APD). This could modify the time course of changes in the APD of premature stimuli (electrical restitution) and affect dispersion of repolarization and homogeneity of refractoriness. The effects of two potent local anesthetic drugs, i.e., flecainide and propafenone, on electrical restitution were studied in canine Purkinje fibers, superfused with Tyrode's solution and impaled with glass microelectrodes. APD was measured at 90% repolarization (APD90): fibers were stimulated for 3 minutes at cycle lengths (CLs) between 350 msec and 1.5 seconds, and kept quiescent for 5 minutes in between. For each run we calculated the percent ratio of the second APD (APD test = APDt) to the first APD after quiescence (APDo) (APDt/APDo x 100). The ratio was correlated with the CL of the run (i.e., the coupling interval between APDo and APDt = CI) by the monoexponential function APDt/APDo x 100 = 100-exp(-tau/CI), whose time constant tau indicates the speed of electrical restitution. At 1 microM, flecainide decreased tau by 26% +/- 4% (to 310 +/- 41 msec from 245 +/- 30 msec, n = 6, P < 0.05), while propafenone did not change it. Thus, unlike propafenone, flecainide slows the process of electrical restitution in Purkinje fibers. This may derive from the drug's action on currents other than Na current (i.e., IK), relevant to the duration of action potential. In a reentrant circuit, despite similar effects on conduction, APD and refractoriness of the first beat would be differently modulated by flecainide and propafenone.
Clinica Medica Generale e Terapia Medica, Istituto Scientifico Ospedale San Luca IRCCS, Italy.
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G
Malfatto
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Zaza
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PJ
Schwartz
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011405:Propafenone / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D000779:Anesthetics, Local; D011405:Propafenone; D005424:Flecainide