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On the mechanisms underlying digitalis toxicity in cardiac Purkinje fibers
Abstract:
The different mechanisms by which digitalis enhances pacemaker automaticity in canine Purkinje fibers has been studied under different conditions. Transmembrane potentials of quiescent, spontaneously active, or electrically driven fibers were recorded in the presence and absence of strophanthidin (10(-5)-10(-7) M). In quiescent fibers, strophanthidin caused the membrane potential to depolarize and to develop oscillations of progressively larger magnitude which were followed by spontaneous activity. In spontaneously active preparations strophanthidin enhanced the slope of diastolic depolarization and therefore the rate of discharge. In both cases, there was no evidence of oscillations during diastolic depolarization. A steepening of diastolic depolarizations without superimposed oscillations (and eventually also followed by spontaneous activity) was observed in preparations driven electrically at very slow rates. However, in fibers driven at faster rates (30/min or more) in the presence of ouabain, oscillations developed during diastolic depolarization. These oscillations were frequency dependent in two respects: 1) at slower rates the oscillations remained constant during the drive, the actual magnitude being proportional to the driving rate; 2) at rate of 60/min or more, the oscillations increased in size with each successive beat. Fast rhythms were initiated by a progressive acceleration of the pacemaker potential or abruptly by an extrasystole. When spontaneous activity ceased, the membrane increased slowly toward the control value. We conclude that digitalis increases the frequency of discharge of Purkinje fibers 1) by enhancing diastolic depolarization when the rate of discharge is slow; 2) by developing a new current which modifies diastolic depolarization when diastole is sufficiently short; and 3) by means of the potassium plateau current when the rate of spontaneous discharge is fast. Whether one or more of these mechanisms are operational in affecting Purkinje fiber automaticity depends critically on the rate of discharge of the fibers.
Insights
Digitalis increases Purkinje fiber automaticity by enhancing diastolic depolarization at slow rates, developing new currents at short diastoles, and utilizing potassium plateau currents at fast rates. These mechanisms depend on fiber discharge rate.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Digitalis glycosides are known to affect cardiac automaticity.
- Purkinje fibers possess inherent pacemaker automaticity.
- Understanding the precise mechanisms of digitalis action on Purkinje fibers is crucial for cardiac electrophysiology.
Purpose of the Study:
- To elucidate the distinct mechanisms by which digitalis enhances pacemaker automaticity in canine Purkinje fibers under varying conditions.
- To investigate the role of strophanthidin and ouabain in modulating Purkinje fiber electrical activity.
- To determine the rate-dependent effects of digitalis on Purkinje fiber discharge frequency.
Main Methods:
- Recording transmembrane potentials of canine Purkinje fibers (quiescent, spontaneously active, or electrically driven).
- Administering strophanthidin (10(-5)-10(-7) M) and ouabain to assess their effects on fiber activity.
- Analyzing changes in membrane potential, depolarization slopes, and oscillatory behavior.
Main Results:
- In quiescent fibers, digitalis induced depolarization and oscillations, leading to spontaneous activity.
- In spontaneously active fibers, digitalis enhanced diastolic depolarization slope, increasing discharge rate without oscillations.
- At faster driven rates, digitalis induced frequency-dependent oscillations during diastolic depolarization, with magnitude related to driving rate.
Conclusions:
- Digitalis enhances Purkinje fiber automaticity through multiple, rate-dependent mechanisms.
- These include enhanced diastolic depolarization at slow rates, a novel current at short diastoles, and the potassium plateau current at fast rates.
- The specific operational mechanism is critically dependent on the fiber's intrinsic discharge rate.