Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome

Abstract

Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β (7-fold), TNF-α (84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold). Heart function ex vivo in MS group showed a decreased mechanical performance response to isoproterenol challenge (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum displayed impaired contractile function and Ca2+ handling during ISO treatment, showing slightly decreased cell shortening and Ca2+ transient amplitude (23%), slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+ release events (7.5-fold). As spontaneous Ca2+ releases provide a substrate for ventricular arrhythmias, our study highlights the possible role of serum proinflammatory mediators in the development of arrhythmic events during MS.

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

“…Intense physical endurance induced atrial arrhythmia susceptibility in rats, via a TNFα-dependent mechanism [71]. IL-17, another pro-inflammatory cytokine, contributes to ischemia-induced arrhythmias in rabbits [72], and IL-1β, TNFα and IL-6 contribute to arrhythmias in rats [73].…”

The Role of Cardiac Macrophage and Cytokines on Ventricular Arrhythmias

“…Clinical studies have revealed that the levels of IL-1β in both tissue and plasma are significantly increased in patients with VAs. These results suggest that in addition to the above biological functions, IL-1β might be an important mediator of ion channel remodeling, thereby producing Vas (Fernández-Sada et al, 2017;Abbate et al, 2020).…”

Shensong Yangxin Protects Against Metabolic Syndrome-Induced Ventricular Arrhythmias by Inhibiting Electrical Remodeling

“…Patients with MetS showed significantly risk of atrial fibrillation ( Nyström et al., 2015 ; Kim et al., 2018 ). It has been demonstrated that MetS increase the risk of ventricular arrhythmia (VA) ( Fernández-Sada et al., 2017 ; Liptak et al., 2017 ). Furthermore, MetS was reported to contribute to higher recurrence rate of outflow tract VA after catheter ablation ( Sardu et al., 2014 ).…”