Effects of lidocaine and on slow response and depressed fast response action potentials of canine cardiac Purkinje fibers.
Disease may decrease resting potential of cardiac fibers, thereby depressing the upstroke velocity of the action potential, causing slow conduction and reentry. A decrease in resting potential may also cause automaticity. We studied the effects of lidocaine (5 and 20 mg/l) on canine Purkinje fibers with reduced membrane potentials with either depressed Na+-dependent upstrokes (depressed fast responses) or with slow inward (Ca++) current-dependent upstrokes (slow responses). Depressed fast responses were produced by elevating [K+]0 in the perfusate, reducing membrane potential to around -60 mV, without abolishing excitability. Slow responses were produced by either perfusing fibers with a Na+-free, Ca++-rich solution, or by perfusing them with a high [K+]0 Tyrode's solution containing norepinephrine. Lidocaine had a marked depressant effect on depressed fast response action potentials. The drug markedly decreased Vmax and conduction velocity. It sometimes decreased action potential amplitude and caused conduction block. Resting potential was not changed. On the other hand, lidocaine had little effect on slow response action potentials. Resting potential, Vmax and action potential amplitude were not altered nor was conduction changed. The rate of spontaneous impulse initiation was slightly reduced by 5 mg/l of lidocaine but not by 20 mg/l. We conclude that lidocaine does not exert its antiarrhythmic effect by directly depressing the slow inward current but may be antiarrhythmic because it depresses an already depressed fast inward current and can cause conduction block.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors
D008012:Lidocaine; D012964:Sodium; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine