Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility

Abstract

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery ( n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, β-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with β1/2 (isoproterenol) or β3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and β1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute β3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific β3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the β3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on β3-adrenergic rather than β1/2-adrenergic stimulation of EAT.

Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium

“…Although recombinant resistin did not enhance the propensity for spontaneous trabeculae contractions, previous research has found that resistin overexpressed within the rat heart significantly depresses in vitro and in vivo contractility (8,17). Furthermore, we and others have shown that cardiac contraction and relaxation kinetics are altered by EAT and subcutaneous 24-h cultured secretomes (1,19,22). Therefore, for the present study, we also assessed the effect of exogenous resistin (7, 12, 20 ng/mL) on human atrial trabeculae developed force, +dF/dt max and ÀdF/dt max .…”

“…b-Adrenergic stimulation is a trigger for in vivo autonomous atrial muscle activity. We have previously validated this in ex vivo human atrial trabeculae, whereby ISO treatment acutely increased the proportion of spontaneously contracting trabeculae as well as the average number of spontaneous contractions exhibited by each trabecula (1). Therefore, we next tested whether resistin treatment enhanced spontaneous trabecula contractions in the presence of an arrhythmogenic ISO trigger (10 À5 M).…”

“…Resistin levels in fresh human EAT. We have previously reported that fresh human EAT enhances myocardial automaticity when placed upstream of the atrial trabeculae and stimulated with the b 3 -adrenergic agonist, BRL37344 (BRL) (1). Therefore, to determine if resistin is released by the fresh EAT and whether this is modulated by BRL stimulation (10 À6 M), the concentration of resistin in the superfusion media before and after BRL addition was measured.…”

“…In CVD, however, the unique proximity and activity of EAT is hypothesized to become detrimental to cardiac health due to an augmented release of proinflammatory EATderived factors (2,20,23). We have recently shown that superfusion of human atrial myocardium with secretome derived from human EAT stimulated with b-adrenergic triggers promotes arrhythmia-like behavior and alters contractility kinetics (1). From our previous work, it was not possible to determine the role of specific EAT-derived adipocytokines.…”

Left Ventricular Summit—Concept, Anatomical Structure and Clinical Significance

“…This distance might impact ventricular potential amplitude recorded from the great cardiac vein if the epicardial adipose tissue is sufficiently thick. Moreover, the thick adipose tissue layer may have a pro-arrhythmogenic activity and negatively influence the success rate of electrophysiological procedures performed within the LVS [40][41][42].…”