Production of slow responses in canine cardiac Purkinje fibers exposed to reduced pH

Abstract

Isolated canine papillary muscle-false tendon tissue preparations were exposed to reduced pH at a level of 6.0 or 5.2. Effects on the transmembrane potential of Purkinje fibers and ventricular muscle fibers were recorded. Ventricular fibers were not significantly altered by these levels of pH relative to the changes observed in Purkinje fibers. In Purkinje fibers acid perfusion initially caused decreases in maximum diastolic potential, rising velocity and overshoot and an increase in duration of the action potential. Subsequently in many fibers these effects progressed and resulted in an action potential with all of the characteristics of what has been termed the “slow response.” The maximum diastolic potential was 50 ± .9 mV, the overshoot was 20 ± 1.1 mV and the action potential duration was 322 ± 11 ms. Phase 4 depolarization of variable degree usually became evident with the onset of slow responses. In a number of experiments the preparation escaped from the drivestimulus and discharged spontaneously at a more rapidrate. In other experiments suspension of drive stimulation resulted in spontaneous discharge of action potentials generated by the mechanism of phase 4 depolarization. Such excitation propagated and caused excitation of other Purkinje fibers as well as ventricular muscle fibers. At times disturbances of conduction were noted and ranged from simple slowing in conduction of excitation to partial or complete block of conduction between regions of the preparation. Agents known to block the slow response were tested for their ability to block pH-induced responses. MnC1 2 or verapamil depressed the upstroke and overshoot of the slow response and slowed or stopped the spontaneous discharge of action potentials in acid medium. The possible role of pH-induced slow responses in causing cardiac arrhythmias, especially those arising secondary to cardiac ischemia, was considered.