Unveiling the Multifaceted Problems Associated with Dysrhythmia

Abstract

Dysrhythmia is a term referring to the occurrence of spontaneous and repetitive changes in potentials with parameters deviating from those considered normal. The term refers to heart anomalies but has a broader meaning. Dysrhythmias may concern the heart, neurological system, digestive system, and sensory organs. Ion currents conducted through ion channels are a universal phenomenon. The occurrence of channel abnormalities will therefore result in disorders with clinical manifestations depending on the affected tissue, but phenomena from other tissues and organs may also manifest themselves. A similar problem concerns the implementation of pharmacotherapy, the mechanism of which is related to the impact on various ion currents. Treatment in this case may cause unfavorable effects on other tissues and organs. Drugs acting through the modulation of ion currents are characterized by relatively low tissue specificity. To assess a therapy's efficacy and safety, the risk of occurrences in other tissues with similar mechanisms of action must be considered. In the present review, the focus is shifted prominently onto a comparison of abnormal electrical activity within different tissues and organs. This review includes an overview of the types of dysrhythmias and the basic techniques of clinical examination of electrophysiological disorders. It also presents a concise overview of the available pharmacotherapy in particular diseases. In addition, the authors review the relevant ion channels and their research technique based on patch clumping.

Keywords: dysrhythmia; electrobiological techniques; patch clamp; pharmacotherapy.

Figure 1

Division of the rhythm of propagation of electrical waves in different organs of the body: (a) heart, (b) brain, (c) stomach.

Figure 2

Diagram of the distributions of action potentials in individual cells of the cardiac stimulus–conduction systems. Summary changes in cardiac action potential are recorded in the form of an electrocardiographic curve (ECG). ECG showing the course of electrical phenomena during normal cardiac activity (healthy heart). The ECG obtained from the surface of the skin is the sum of the potentials conducted in the working heart. It is possible to record potentials in individual structures of the conduction system of the heart during electrophysiological examination. The QT interval includes the duration of depolarization (QRS complex) and repolarization (ST segment and T-wave) of heart muscle cells. A normal QT interval is defined as less than 450 [ms] in men and less than 460 [ms] in women [9]. Prolongation of the QT interval (LQTS syndrome) is indicative of a slowing of the repolarization process, meaning that the return to the resting membrane potential value after the depolarization of cardiomyocytes is delayed. This favors the occurrence of polymorphic ventricular tachycardia of the torsade de pointes type clinically referred to as torsade de pointes ventricular arrhythmia (TdP), which can cause syncope and sudden cardiac death in healthy, young individuals [9].

Figure 3

Main channelopathies associated with epilepsy and arrhythmias [35].

Figure 4

Classification scheme of antiarrhythmic drugs according to Vaughan Williams. Part (A) shows action potential in Purkinje fiber and SA node (where DE is depolarization, RE is repolarization, PP stands for pacemaker potential, RR is relative refractory period, AR is absolute refractory period, ↑↓ denotes flow of ions across membrane, and (0), (1), (2), (3), and (4) indicate phases of the cardiac action potential). Normally, the rate of discharge of the SA node maintains a heart rate between 60–100 bpm. Slower rates of discharge occur in the atrioventricular node (40 and 60 bpm) or Purkinje system (20–40 bpm); however, these slower rates are normally controlled by the dominant pacemaker, which has a higher intrinsic rate of discharge. Greater automaticity results in a higher rate of action potential discharge [80]. Part (B) presents classes and examples of antiarrhythmic drugs according to Vaughan Williams; Part (C) displays the clinical use of antiarrhythmic drugs.