A Comparison of the Effects of Halothane and Tetrodotoxin on the Regional Repolarization Characteristics of Canine Purkinje Fibers

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Abstract
The effects of halothane, tetrodotoxin (TTX), veratridine (VTD), and alterations of extracellular calcium ion concentration ([Ca++]o) on regional differences of canine Purkinje fiber action potential duration (APD50 and APD90) were investigated in vitro at a paced rate of 75 beats per min. Under control conditions (n = 15 hearts) APD90 of proximal (false tendon) fibers (289 .+-. 6 ms) always exceeded (P .ltoreq. 0.01) that of distal (apical) fibers (213 .+-. 4 ms). Halothane (0.35-1.07 mM) reduced regional differences of APD90 by producing dose-dependent decreases of proximal APD90 without decreases of distal APD90. The regional actions of halothane were similar to those of low (0.33-1.0 .mu.M) concentrations of the Na+ channel antagonist TTX, which also decreased proximal APD90 more than distal APD90. The actions of halothane in combination with TTX further decreased proximal APD90, whereas the Na+ channel agonist VTD, which increased proximal APD90 more than distal APD90, reversed the regional actions of halothane. Decreasing Ca++ influx by reducing [Ca++]o from 1.8 to 0.6 mM increased proximal APD90 more than distal APD90 in a manner opposite to the regional actions of halothane. Although there was no difference between the values of APD90 obtained for each region in the presence of halothane at 0.6, 1.8, and 3.6 mM [Ca++]o, the action of halothane decreasing APD90 of proximal fibers was more prominent at 0.6 mM [Ca++]o because of the increased APD90 of fibers under this condition. The findings are consistent with, but do not definitively prove, the hypothesis that halothane may decrease APD90 of proximal Purkinje fibers by a mechanism similar to that of TTX involving inhibition of plateau-phase inward Na+ current.