Inhibition by enflurane and methoxyflurane of postdrive hyperpolarization in canine Purkinje fibers.
When a pacemaker cell is driven with a train of stimuli at a rate faster than its own, the termination of the drive is followed by a transient hyperpolarization, due to the activity of an electrogenic Na+-K+ pump. In this study, the effect of the halogenated ethers, enflurane and methoxyflurane, on postdrive hyperpolarization (PDH) was determined in cardiac Purkinje fibers. The fibers were removed from freshly excised canine hearts and superfused with a Tyrode's solution (containing 2.7 or 3.5 mM K+). The preparation was paced at 0.2 Hz before and after drives, and at 2 Hz during drives. Under control conditions, drives of 2 min produced a PDH of 5.5 +/- 0.2 mV. Enflurane (1.5-5%) significantly reduced the PDH. At 4 to 5%, enflurane reduced the PDH to a mean value of 42% of the control. Methoxyflurane was more potent than enflurane in affecting the PDH. At 0.5 to 0.75%, methoxyflurane reduced the PDH to 5% of the control. At higher (1-1.5%) concentrations of methoxyflurane, the PDH was converted to a depolarization, which varied between 0.5 and 8.0 mV. The PDH was restored to control levels within 10 to 20 min after washout of either anesthetic agent. Methoxyflurane (0.5 or 1%) enhanced the automaticity of spontaneously firing cells (2.35 mM K+ Tyrode's solution used). This positive chronotropic action coincided with a depolarization of 2 to 8 mV. Enflurane, at concentrations of 3 to 5%, gave similar results. On the action potential, methoxyflurane, at 1%, reduced the amplitude and duration (measured at 50% repolarization) of the plateau, and also the maximal upstroke velocity (+Vmax) of the rising phase.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008733:Methoxyflurane / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D008733:Methoxyflurane; D004737:Enflurane; D012964:Sodium; D011188:Potassium; D004837:Epinephrine