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The antiarrhythmic and antifibrillatory effects of calcium antagonists
1Department of Physiology, Ohio State University, Columbus 43210.
Insights
Calcium-channel antagonists can prevent dangerous ventricular arrhythmias by regulating calcium levels in heart cells. These drugs offer potential cardioprotection against sudden cardiac death, independent of blood vessel effects.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Ventricular arrhythmias stem from abnormal impulse generation and conduction.
- Calcium ions play a crucial role in both arrhythmogenic mechanisms.
- Myocardial ischemia and sympathetic activation increase cytosolic calcium, provoking arrhythmias.
Purpose of the Study:
- To explore the underappreciated benefits of calcium-channel antagonists in managing ventricular arrhythmias.
- To elucidate the role of calcium ions in the pathophysiology of ventricular arrhythmias.
- To highlight the potential of calcium antagonists in preventing sudden cardiac death.
Main Methods:
- Review of existing literature on calcium-channel antagonists and ventricular arrhythmias.
- Analysis of the mechanisms by which calcium ions influence cardiac impulse generation and conduction.
- Examination of studies investigating the effects of calcium antagonists on myocardial ischemia-induced arrhythmias.
Main Results:
- Elevated cytosolic calcium can trigger oscillatory depolarizations and sustained action potentials, leading to ventricular arrhythmias.
- Myocardial ischemia causes dispersion of refractory periods, creating re-entrant circuits and ventricular fibrillation.
- Calcium-channel antagonists have demonstrated the ability to prevent afterdepolarizations and reduce refractory period dispersion during ischemia.
Conclusions:
- Calcium-channel antagonists may prevent malignant ventricular arrhythmias by stabilizing cardiac membrane potential and reducing refractory period dispersion.
- A slow inward calcium current appears necessary for the initiation and maintenance of ventricular fibrillation.
- Cardioprotection by calcium antagonists is independent of vascular smooth muscle effects, suggesting direct myocardial actions are key for preventing sudden cardiac death.
Abstract:
Calcium-channel antagonists are widely used in the treatment of supraventricular tachyarrhythmias. The potential benefits of these agents in the management of ventricular arrhythmias, however, are not widely appreciated. Ventricular arrhythmias result from abnormalities of impulse generation and/or impulse conduction. The calcium ion has been implicated in both mechanisms. Myocardial cytosolic calcium increases during ischemia and sympathetic nervous system activation. Elevations in cytosolic calcium provoke oscillatory depolarizations of the cardiac membrane, triggering sustained action potential generation and extrasystoles. Myocardial ischemia also results in a dispersion of refractory period, producing random re-entrant circuits and ventricular fibrillation. Alterations in action potential duration that produce this dispersion of refractory period are associated with spatial and temporal nonuniformities of intracellular calcium transients. Calcium-channel antagonists have been shown to prevent afterdepolarizations and to reduce the endocardial to epicardial dispersion of the refractory period during myocardial ischemia, and therefore could prevent malignant arrhythmias. A slow inward calcium current may, in fact, be required for the initiation and maintenance of ventricular fibrillation. Calcium antagonists reduce, whereas calcium agonists enhance, the susceptibility to ventricular fibrillation induced by the combination of exercise and acute myocardial ischemia. The cardioprotection occurs independently of actions on vascular smooth muscle. Thus, calcium antagonists that exert direct myocardial actions may prove to be particularly effective in the prevention of sudden cardiac death in patients. The challenge remains to develop calcium antagonists that selectively modulate myocardial calcium entry without compromising cardiac mechanical function.