Electrically-Induced Ventricular Fibrillation Alters Cardiovascular Function and Expression of Apoptotic and Autophagic Proteins in Rat Hearts

Abstract

Background: The pathological heart contractions, called arrhythmias, especially ventricular fibrillation (VF), are a prominent feature of many cardiovascular diseases leading to sudden cardiac death. The present investigation evaluates the effect of electrically stimulated VF on cardiac functions related to autophagy and apoptotic mechanisms in isolated working rat hearts. Methods: Each group of hearts was subjected to 0 (Control), 1, 3, or 10 min of spacing-induced VF, followed by 120 min of recovery period and evaluated for cardiac functions, including aortic flow (AF), coronary flow (CF), cardiac output (CO), stroke volume (SV), and heart rate (HR). Hearts were also evaluated for VF effects on infarcted zone magnitude and Western blot analysis was conducted on heart tissue for expression of the apoptotic biomarker cleaved-caspase-3 and the autophagy proteins: p62, P-mTOR/mTOR, LC3BII/LC3BI ratio, and Atg5-12 complexes. Results: Data revealed that VF induced degradation in AF, CF, CO, and SV, which prominently included-variable post-VF capacity for recovery of normal heart rhythm; increased extent of infarcted heart tissue; altered expression of cleaved-caspase-3 suggesting potential for VF-mediated amplification of apoptosis. VF influence on expression of p62, LC3BII/LC3BI, and Atg5-12 proteins was complex, possibly due to differential effects of VF-induced expression on proteins comprising the autophagic program. Conclusions: VF was observed to cause time-dependent changes in autophagy processes, which with additional analysis under ongoing investigations, likely to yield novel therapeutic targets for the prevention of VF and sudden cardiac death.

ArrhythmoGenoPharmacoTherapy

“…Potential mechanisms depicted in Figure 3 show that reperfusion of the ischemic myocardium intensifies the incidence of reperfusion-induced arrhythmias, which are followed by necrosis-, apoptosis-, and autophagy-induced cell deaths (Osipov et al, 2009;Zhang et al, 2012;Chang et al, 2013;Czegledi et al, 2019;Gyongyosi et al, 2019;Yasuda et al, 2019). From a different point of view, autophagic processes may be even beneficial, depending on their intensity in reversible injured myocardial cells.…”

“…From a different point of view, autophagic processes may be even beneficial, depending on their intensity in reversible injured myocardial cells. However, necrosis-induced cell death could dominate and mask autophagic signal transduction processes and autophagyinduced cell death in myocardial tissues (Czegledi et al, 2019;Gyongyosi et al, 2019). Cellular biology and genetics have a real value and significant impact to try better to define the generation of cardiovascular diseases, including life threatening cardiac arrhythmias.…”

The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy

“…The autophagic, apoptotic, and necrotic cell death pathways play important roles not only in skeletal muscle but also in cardiac tissues [37][38][39]. Impaired autophagy can lead to the premature death of cardiomyopathy and myocardium [40].…”

Correlation between increased atrial expression of genes related to fatty acid metabolism and autophagy in patients with chronic atrial fibrillation

“…In addition, animal studies have shown that onset of ventricular fibrillation increases autophagy-associated proteins in the ventricle accompanied by myocardial damage [24][25][26], suggesting that arrhythmia itself may directly cause altered cardiac autophagy.…”