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

Autor: Martin K. Stiles, Isabelle van Hout, Richard W. Bunton, Peter P. Jones, Regis R. Lamberts, Ingrid C. Fomison-Nurse, Ramanen Sugunesegran, Philip Davis, Sean Coffey, Hamish M. Aitken-Buck, Aram A. Babakr, Michael J.A. Williams
Rok vydání: 2019
Předmět:
Zdroj: American journal of physiology. Endocrinology and metabolism. 318(2)
ISSN: 1522-1555
Popis: 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.
Databáze: OpenAIRE