A2 Adenosine Receptor Subtypes Overproduction in Atria of Perioperative Atrial Fibrillation Patients Undergoing Cardiac Surgery: A Pilot Study

Abstract

Objective: Although atrial fibrillation is a common cardiac arrhythmia in humans, the mechanism that leads to the onset of this condition is poorly elucidated. Adenosine is suspected to be implicated in the trigger of atrial fibrillation (AF) through the activation of its membrane receptors, mainly adenosine receptor (AR) subtypes A1R and A2R. In this study, we compared blood adenosine concentration (BAC), and A1R, A2AR, and A2BR production in right (RA) and left atrium (LA), and on peripheral blood mononuclear cells (PBMCs) in patients with underlying structural heart disease undergoing cardiac surgery with or without peri-operative AF (PeOpAF).Methods: The study group consisted of 39 patients (30 men and 9 women, mean age, range 65 [40–82] years) undergoing cardiac surgery and 20 healthy patients (8 women and 12 men; mean age, range 60 [39–72] years) as controls were included. Among patients, 15 exhibited PeOpAF.Results: Blood adenosine concentration was higher in patients with PeOpAF than others. A2AR and A2BR production was higher in PBMCs of patients compared with controls and was higher in PeOpAF patients than other patients. In LA and RA, the production of A2AR and A2BR was higher in patients with PeOpAF than in other patients. Both A2AR and A2BR production were higher in LA vs. RA. A1R production was unchanged in all situations. Finally, we observed a correlation between A1R, A2AR, and A2BR production evaluated on PBMCs and those evaluated in LA and RA.Conclusions: Perioperative AF was associated with high BAC and high A2AR and A2BR expression, especially in the LA, after cardiac surgery in patients with underlying structural heart disease. Whether these increases the favor in triggering the AF in this patient population needs further investigation.

Adenosine Receptors Profile in Fibromuscular Dysplasia

“…Interestingly, while high A 2A R and high ABL in VVS seem to participate in the cause of the disease, since high A 2A production and a specific polymorphism in A 2A R gene are associated with VVS suggesting a genetic predisposition [ 35 ], the increase in these parameters in CCF or in cardiogenic shock seems rather an adaptive mechanism. Both high ABL and A 2B R overproduction have been reported in patients with atrial fibrillation (AF) [ 36 ]. However, if the increase in A 2B production participates in the AF process or if conversely it is an adaptive mechanism that remains unknown.…”

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

“…A 2B Rs are expressed in coronary arteries and mediates coronary vasodilation, with a minor and supportive role compared to A 2A R [ 50 ]. The expression of A 2B Rs has also been reported in atrial and ventricular cardiomyocytes [ 35 , 47 ]. A 2B Rs’ activation on cardiac fibroblasts reduces collagen and total protein synthesis suggesting that adenosine may protect against cardiac fibrosis [ 51 ].…”

“…This is especially useful as a cardioprotection in ischemia-reperfusion injury [ 41 , 42 ]. A 2A Rs are particularly expressed in vessels and coronary arteries with a vasodilator effect [ 43 , 44 ], whereas their density is moderate in ventricular and atrial tissues, leading to the contraction of cardiomyocytes [ 45 , 46 , 47 ]. Opposite to A 1 R, A 2A R directly enhanced the inotropic effect of cardiomyocyte by increasing the cytosolic Ca 2+ level and the Ca 2+ sensitivity of the myofilaments [ 48 ].…”

“…The expression of adenosine receptors is modified in AF. Our team recently described the upregulation of A 2A R and A 2B R expressions in the left and right atrium in postoperative AF [ 47 ]. This overexpression was significantly higher in the left atrium than in the right atrium [ 47 ].…”

“…Our team recently described the upregulation of A 2A R and A 2B R expressions in the left and right atrium in postoperative AF [ 47 ]. This overexpression was significantly higher in the left atrium than in the right atrium [ 47 ]. Li et al also showed the upregulation of A 1 R in AF, especially in the right atrium [ 72 ].…”