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Electrophysiological effects of left ventricular hypertrophy. Effect of calcium and potassium channel blockade
P R Kowey1, T D Friechling, J Sewter
1Cardiovascular Research Laboratory, Medical College of Pennsylvania, Philadelphia.
Insights
Left ventricular hypertrophy (LVH) increases vulnerability to ventricular fibrillation by altering electrical recovery. Blocking potassium channels, but not calcium channels, protects against this arrhythmia.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Left ventricular hypertrophy (LVH) can lead to cardiac arrhythmias.
- The arrhythmogenic effects of LVH require detailed electrophysiological investigation.
Purpose of the Study:
- To define the arrhythmogenic effects of LVH in an intact heart model.
- To assess the impact of calcium and potassium channel blockade on LVH-induced arrhythmias.
Main Methods:
- Electrophysiological assessment in a feline aortic-banding model of LVH.
- Measurement of conduction times, excitability, refractoriness, and action potential duration.
- Evaluation of ventricular fibrillation (VF) vulnerability and thresholds.
Main Results:
- LVH cats exhibited increased vulnerability to VF, spontaneous VF, and lower VF thresholds compared to controls.
- LVH caused greater dispersion of effective refractory period and action potential duration.
- Risotilide (potassium channel blocker) reduced dispersion and ventricular vulnerability; verapamil (calcium channel blocker) had no significant effect.
Conclusions:
- LVH significantly increases ventricular vulnerability to fibrillation by promoting dispersion of refractoriness and repolarization.
- Voltage-dependent potassium channel blockade mitigates LVH-induced arrhythmogenesis.
- Slow inward calcium channel blockade does not protect against LVH-related ventricular fibrillation.
Background:
To define the arrhythmogenic effects of left ventricular hypertrophy (LVH) in the intact heart, we carried out a detailed electrophysiological assessment in our previously validated feline aortic-banding model and then tested the effects of agents that blocked either the slow inward calcium or voltage-dependent potassium channel.
Methods And Results:
We measured intraventricular and interventricular conduction times, excitability thresholds, ventricular effective refractory periods, and monophasic action potential duration at several sites in cats with LVH as well as in concurrent control (sham-operated) cats. In addition, we assessed vulnerability to ventricular arrhythmia using direct measurement of ventricular fibrillation (VF) thresholds and by standard techniques of programmed stimulation. Despite finding no difference between LVH and sham-operated cats in mean values for several electrophysiological parameters, the former group was significantly more vulnerable to VF, with more spontaneous VF and lower VF thresholds. Compared with the sham controls, LVH cats also had a greater dispersion of effective refractory period (35 +/- 11 versus 12 +/- 4 msec, p less than 0.01) and monophasic action potential duration at 90% repolarization (69 +/- 25 versus 39 +/- 7 msec, p less than 0.02). Verapamil had no significant effect on these electrophysiological parameters, nor did it affect VF threshold. However, risotilide, an inhibitor of the voltage-dependent potassium channel, narrowed dispersion of the effective refractory period and monophasic action potential duration concomitant with a marked reduction in ventricular vulnerability.
Conclusions:
LVH has a pronounced effect on dispersion of refractoriness and repolarization and renders the ventricle more vulnerable to fibrillation. Blockade of the voltage-dependent potassium channel, but not the slow inward calcium channel, narrows the dispersion of recovery of excitability and protects against VF.
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