Electrophysiological effects of tocainide on canine subendocardial Purkinje fibers surviving infarction
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Abstract:
The effects of 10 and 20 mg/l of tocainide on transmembrane action potential characteristics were examined in Purkinje fibers surviving infarction. Infarcted tissue was obtained from canine hearts 24 h after coronary artery ligation. The preparation was stimulated at basic cycle lengths (BCL) of 1000-300 ms. Tocainide reduced the overshoot and amplitude of Purkinje fibers surviving infarction. The maximum upstroke velocity (Vmax) was decreased by tocainide in a dose dependent manner. This effect was more prominent at the shorter BCL. Statistical analysis revealed a significant interaction of the BCL with the drug effect on overshoot, amplitude, Vmax and action potential durations (APD50% and APD90%). Tocainide reduced the effective refractory period (ERP) at the BCL of 1000 ms, but had no significant effect at the BCL of 300 ms. Membrane responsiveness and steady state characteristics of Vmax were shifted significantly to more negative membrane potentials by tocainide. Investigation of the recovery kinetics of Vmax in the presence of tocainide showed an exponential recovery of Vmax with a time constant of 514 ms. These results support the finding that the effect of tocainide on Vmax and conductions is enhanced at faster rates of stimulation. Thus tocainide may be able to depress conduction to produce bidirectional block in the termination of ventricular tachycardia caused by reentry, while having minimal effect on conduction at normal heart rates.
Insights
Tocainide effectively reduces conduction in Purkinje fibers after heart attack, especially at faster rates. This antiarrhythmic effect may help terminate ventricular tachycardia by blocking reentry pathways.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Pharmacology
Background:
- Myocardial infarction can lead to life-threatening arrhythmias.
- Purkinje fibers play a crucial role in cardiac conduction and are affected by infarction.
- Antiarrhythmic drugs are essential for managing post-infarction cardiac electrical instability.
Purpose of the Study:
- To investigate the effects of tocainide on the electrophysiological properties of Purkinje fibers in infarcted canine hearts.
- To determine the dose-dependent and rate-dependent effects of tocainide on action potential characteristics.
- To assess tocainide's potential to modulate conduction and terminate reentry arrhythmias.
Main Methods:
- Electrophysiological recordings of transmembrane action potentials in canine Purkinje fibers surviving infarction.
- Application of tocainide at concentrations of 10 and 20 mg/l.
- Stimulation at various basic cycle lengths (BCLs) from 1000 ms to 300 ms.
- Analysis of action potential parameters including overshoot, amplitude, maximum upstroke velocity (Vmax), action potential durations (APD50%, APD90%), and effective refractory period (ERP).
Main Results:
- Tocainide significantly reduced action potential overshoot, amplitude, and Vmax in a dose-dependent manner.
- The effects of tocainide on electrophysiological parameters were more pronounced at shorter BCLs (faster heart rates).
- Tocainide decreased the effective refractory period at a BCL of 1000 ms but not at 300 ms, indicating rate-dependent effects on refractoriness.
Conclusions:
- Tocainide's antiarrhythmic effects, particularly on conduction velocity (Vmax), are enhanced at faster heart rates.
- These findings suggest tocainide can depress conduction, potentially inducing bidirectional block to terminate reentry-induced ventricular tachycardia.
- Tocainide demonstrates a favorable profile with minimal impact on conduction at normal heart rates, while effectively targeting abnormal conduction during tachycardia.
