Pharmacologic management of arrhythmias.
Year: 2011
Type: article
Abstract: Understanding the mechanisms by which individual antiarrhythmic agents work requires a detailed understanding of the cardiac action potential (AP). The AP of the ventricular myocyte has 5 phases (0 to 4) and is the standard model of the cardiac AP. At baseline (phase 4, also known as the resting membrane potential), the intracellular environment is negatively charged, compared with that of the extracellular space (−96 mV). This phase is associated with cardiac diastole. The AP is the result of synchronized influx and efflux of multiple cations and anions. Briefly, this gradient is the sum of 3 main factors: 1) an ATPase sodium/potassium (Na/K) pump; 2) the plasma membrane's impermeability to negatively charged intracellular proteins, which prevents their efflux; and 3) chemical properties (best described by the Nernst equation) that are a consequence of various ion channel permeabilities. For simplicity's sake and the purposes of this discussion, we will mention only those ion channel activities that are relevant to the drugs discussed in this review.
During phase 0 (rapid depolarization), fast sodium (Na+) channels open, which results in rapid inward conductance of Na+ and a rapid influx of Na+ ions into the cell, rendering the intracellular space positive relative to the extracellular milieu. Recovery of the resting membrane starts during phase 1 but is most pronounced during phase 3, when positive currents, primarily in the form of K ions, leave the cell through the delayed rectifier K+ channels (rapid repolarization). The most important reminder about antiarrhythmic treatments can be summarized as follows: Activation of the myocardial cells is due to the rapid inward sodium current, while relaxation or repolarization is mainly due to potassium efflux from the cell.
Figures 1 and and22 demonstrate the correlation between these currents and the surface measurements of these activations as shown by the P, QRS, and T waves. The sodium-dependent (inward current) depolarization of ventricular cells can best be thought of as the QRS complex on the surface electrocardiogram. For this reason, any drug that affects this inward sodium current can also affect the QRS. If it delays the influx of Na+, the QRS is widened; conversely, any agent that delays potassium efflux (and a return to the baseline state) delays the recovery phase or repolarization. For ventricular cells, this delay manifests itself electrocardiographically as a longer QT interval.
Fig. 1 The phases of the cardiac action potential.
Fig. 2 The electrocardiogram and relative ion flow in cardiac cells.
According to the Singh and Vaughan Williams classification of antiarrhythmic agents,1 there are 5 main classes: class I agents, which are Na+-channel blockers; class II agents, which are antisympathetic nervous system agents, most of which are β-blockers; class III agents, which affect the K+ channels; class IV agents, which affect the calcium (Ca2) current and the atrioventricular (AV) node; and class V agents, which work by other (or unknown) mechanisms of action. Our emphasis will be on the class I and III agents and on some of the class V agents.
Source: PubMed
Institution: Baylor St. Luke's Medical Center
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1517880398