Does if control normal automatic rate in canine cardiac Purkinje fibers? Studies on the negative chronotropic effects of lidoflazine.
Lidoflazine has been reported to decrease the conductance of the slow inward current and of the pacemaker current (if) in cardiac tissues. We studied the effects of lidoflazine on normal and abnormal automaticity in isolated preparations of canine and ovine cardiac Purkinje fibers. Normal automaticity occurred in fibers with maximum diastolic potentials (MDPs) greater than -85 mV, and abnormal automaticity occurred in fibers with MDPs less than -60 mV. Normal automaticity was studied in fibers superfused with Tyrode's solution containing 2.7 mM KCl, 4 mM KCl, 4 mM KCl with 1 microM isoproterenol (ISO), and 4 mM KCl with 25 microM BaCl2. In each experiment, normal automatic rate was stable for at least 30 min before lidoflazine was added to the superfusate; lidoflazine did not decrease the rates significantly in any of the four series of experiments. However, when fibers with normal MDPs were pretreated with lidoflazine, the drug blunted the increase in rate that occurred 12-15 min after the start of exposure to ISO. However, lidoflazine significantly decreased abnormal automaticity induced by barium (250 microM or 5 mM). The results indicate that normal automaticity in Purkinje fibers is not affected by lidoflazine and is probably not controlled by if. Rather, normal rate is controlled by the magnitude of background potassium conductance (gK), as indicated by the significant effects of barium (25 microM) on rate. Lidoflazine may blunt the effects of ISO on rate by inhibiting if, but after ISO rhythms are established, they are probably maintained by triggered impulses that are not affected by lidoflazine. Lidoflazine may slow abnormal automaticity by inhibition of the slow inward current.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003864:Depression, Chemical; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008013:Lidoflazine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep
D007552:Isotonic Solutions; D010879:Piperazines; C037692:Tyrode's solution; D001464:Barium; D008013:Lidoflazine; D007545:Isoproterenol; D011188:Potassium