Mechanisms Underlying Antiarrhythmic Properties of Cardioprotective Agents Impacting Inflammation and Oxidative Stress

Abstract

The prevention of cardiac life-threatening ventricular fibrillation and stroke-provoking atrial fibrillation remains a serious global clinical issue, with ongoing need for novel approaches. Numerous experimental and clinical studies suggest that oxidative stress and inflammation are deleterious to cardiovascular health, and can increase heart susceptibility to arrhythmias. It is quite interesting, however, that various cardio-protective compounds with antiarrhythmic properties are potent anti-oxidative and anti-inflammatory agents. These most likely target the pro-arrhythmia primary mechanisms. This review and literature-based analysis presents a realistic view of antiarrhythmic efficacy and the molecular mechanisms of current pharmaceuticals in clinical use. These include the sodium‑glucose cotransporter-2 inhibitors used in diabetes treatment, statins in dyslipidemia and naturally protective omega-3 fatty acids. This approach supports the hypothesis that prevention or attenuation of oxidative and inflammatory stress can abolish pro-arrhythmic factors and the development of an arrhythmia substrate. This could prove a powerful tool of reducing cardiac arrhythmia burden.

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

“…Evidence shows that inflammation and myocardial fibrosis can increase the risk of developing arrhythmias ( 85 , 86 ). Several anti-fibrotic and anti-inflammatory agents were shown to have antiarrhythmic action through limiting pro-arrhythmia substrates such as post-infarct myocardial fibrosis and remodeling ( 87 , 88 ). These drugs mostly have other cardioprotective effects, and though their antiarrhythmic efficacy has not been approved yet, they might be considered as potential therapeutic choices ( 88 ).…”

“…Several anti-fibrotic and anti-inflammatory agents were shown to have antiarrhythmic action through limiting pro-arrhythmia substrates such as post-infarct myocardial fibrosis and remodeling ( 87 , 88 ). These drugs mostly have other cardioprotective effects, and though their antiarrhythmic efficacy has not been approved yet, they might be considered as potential therapeutic choices ( 88 ). Such cardioprotective non-antiarrhythmic drugs with potential antiarrhythmic action are classified as upstream target modulators in the modernized AADs classification ( 7 ).…”

Cardiac Cx43 Signaling Is Enhanced and TGF-β1/SMAD2/3 Suppressed in Response to Cold Acclimation and Modulated by Thyroid Status in Hairless SHRM

“…In contrast to AP, the activity of dipeptidyl peptidase-4 (DPP4), confined to the venous part of heart capillaries, was significantly reduced in hairless SHR M , regardless of the sex, but not in wild type SHR when compared to WKY rat hearts. Vascular DPP4 is a transmembrane serine protease that degrades vasoactive peptides and hormones and is also involved in collagen metabolism [ 30 ] and proinflammatory processes [ 31 ], while the inflammation deteriorates the Cx43 channel function [ 32 ]. Lower DPP4 activity attenuated capillary rarefaction and myocardial inflammation and contributed to a favorable metabolism in an ischemic heart [ 33 ].…”

Distress-Mediated Remodeling of Cardiac Connexin-43 in a Novel Cell Model for Arrhythmogenic Heart Diseases

“…Besides a multitude of mutations affecting different ion channels and their functions, there are many more reasons and acquired conditions that can lead to the development of arrhythmias, comprising systemic diseases such as diabetes, hypertension or the natural process of ageing. However, in principle, the diverse diseases converge at the cellular level and lead to dysfunction of the cell-to-cell junctions, and as a consequence, to alterations of electrical signal propagation across the cardiac muscle [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

“…Stressful stimuli can be of different characters, e.g., prolonged periods of tachycardia as observed in patients with high blood pressure or mental stress. At the cellular level, chronic stress is associated with inflammation and elevated levels of reactive oxygen species (ROS) [ 6 ].…”