Rate-dependent changes in excitability of depressed cardiac Purkinje fibers as a mechanism of intermittent bundle branch block.

Author:

Jalife J,Antzelevitch C,Lamanna V,Moe G K

Abstract

When the heart rate is accelerated, rate-dependent intraventricular block may occur. This block has been attributed to abnormal action potential prolongation in a diseased conducting pathway. Less often, intraventricular block develops during slowing of the heart rate and has been explained in terms of phase 4 depolarization in potentially automatic cells within the diseased fascicle. We tested these hypotheses in isolated bundles of Purkinje fibers placed in a three-chambered tissue bath. In one group of experiments, conditions of localized injury and depressed excitability were mimicked by superfusing the central segment with sucrose solution. Action potentials were initiated in the proximal segment while the slope of phase 4 of cells in the distal end was controlled by intracellular ramps of current of either polarity. In these preparations, phase 4 depolarization facilitated rather than retarded propagation across the depressed segment, even at takeoff potentials as low as -45 mV. In a second group, depressed excitability was induced by exposing the three fiber segments to Tyrode's solution that contained high concentrations of KCl and CaCl2 or isoproterenol (0.1 microgram/ml). Under these conditions, Purkinje fibers did not undergo phase 4 depolarization and did not generate abnormally prolonged action potentials. These preparations showed a biphasic time dependence of conduction during premature stimulation or in response to changes in the basic cycle length. Conduction impairment and block were manifest at either side of an optimal interval or cycle length. Our results suggest that phase 4 depolarization and abnormally prolonged action potentials are not necessary conditions for intermittent block. Both tachycardia and bradycardia-dependent intraventricular conduction abnormalities may be associated with time-dependent variations in the excitability of depolarized conducting fibers as well as in the amplitude of the slow responses generated by these fibers. These alterations can be explained in terms of regulation of slow inward current by the intracellular calcium concentration.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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