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Ionic mechanisms of ischemia-related ventricular arrhythmias
V Ducceschi1, G Di Micco, B Sarubbi
1Cardiology Department, Faculty of Medicine and Surgery, Second University of Naples, Italy.
Insights
This review simplifies the cellular electrophysiology of ischemia-related arrhythmias, detailing therapeutic strategies targeting abnormal impulse generation and conduction for better arrhythmia management.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Myocardial infarction can lead to arrhythmias due to abnormal impulse generation (automaticity, triggered activity) or conduction (reentry).
- Early and delayed afterdepolarizations (EADs and DADs) contribute to triggered activity, influenced by calcium currents.
- Reentry, a common cause of arrhythmias in acute and chronic ischemia, is often dependent on sodium channels.
Purpose of the Study:
- To simplify the cellular electrophysiologic basis of ischemia-related arrhythmias.
- To outline therapeutic interventions for arrhythmias arising from abnormal automaticity and conduction abnormalities.
- To provide a simplified overview of antiarrhythmic drug mechanisms in ischemic conditions.
Main Methods:
- Review of cellular electrophysiologic mechanisms underlying ischemia-related arrhythmias.
- Analysis of therapeutic targets including ion channels (calcium, potassium, sodium) and action potential characteristics.
- Categorization of antiarrhythmic strategies based on arrhythmia type (automaticity vs. reentry) and electrophysiologic parameters (refractory period, excitable gap).
Main Results:
- Arrhythmias from abnormal automaticity can be managed by counteracting calcium influx (calcium antagonists) or increasing potassium efflux (potassium-channel openers).
- Triggered activity therapies focus on shortening repolarization or suppressing inward currents using potassium-channel openers, calcium antagonists, or magnesium.
- Reentrant arrhythmias are treated based on the excitable gap: prolonging refractory period (potassium-channel blockers) for short gaps, and depressing excitability/conduction (sodium-channel blockers) for long gaps.
Conclusions:
- Understanding the electrophysiologic basis of ischemia-related arrhythmias guides targeted therapeutic interventions.
- Pharmacologic strategies involve modulating ion channel activity to correct abnormal automaticity and conduction.
- Specific drug classes, like sodium-channel and potassium-channel blockers, are chosen based on the electrophysiologic characteristics of the reentrant circuit.
Abstract:
The aim of this review is the utmost simplification of the cellular electrophysiologic background of ischemia-related arrhythmias. In the acute and subacute phase of myocardial infarction, arrhythmias can be caused by an abnormal impulse generation, abnormal automaticity or triggered activity caused by early or delayed afterdepolarizations (EAD and DAD), or by abnormalities of impulse conduction (i.e., reentry). This paper addresses therapeutic intervention aimed at preventing the depolarization of "pathologic" slow fibers, counteracting the inward calcium (Ca) influx that takes place through the L-type channels (Ca antagonists), or hyperpolarizing the diastolic membrane action potential, increasing potassium (K) efflux (K-channel openers) in arrhythmias generated by an abnormal automaticity (ectopic tachycardias or accelerated idioventricular rhythms). If the cause enhanced impulse generation is related to triggered activity, and since both EAD and DAD are dependent on calcium currents that can appear during a delayed repolarization, the therapeutic options are to shorten the repolarization phase through K-channel openers or Ca antagonists, or to suppress the inward currents directly responsible for the afterdepolarization with Ca blockers. Magnesium seems to represent a reasonable choice, as it is able to shorten the action potential duration and to function as a Ca antagonist. Abnormalities of impulse conduction (re-entry) account for the remainder of arrhythmias that occur in the acute and subacute phase of ischemia and for most dysrhythmias that develop during the chronic phase. Reentrant circuits due to ischemia are usually Na channel-dependent. Drug choice will depend on the length of the excitable gap: in case of a short gap (ventricular fibrillation, polymorphic ventricular tachycardia, etc.), the refractory period has been identified as the most vulnerable parameter, and therefore a correct therapeutic approach will be based on drugs able to prolong the effective refractory period (K-channel blockers, such as class III antiarrhythmic drugs); on the other hand, for those arrhythmias characterized by a long excitable gap (most of the monomorphic ventricular tachycardias), the most appropriate therapeutic intervention consists of depressing ventricular excit-ability and conduction by use of sodium-channel blockers such as mexiletine and lidocaine. Compared with other class I antiarrhythmic agents, these drugs minimally affect refractoriness and exhibit a use-dependent effect and a voltage dependent action (i.e., more pronounced on the ischemic tissue because of its partial depolarization).