Blockade of A2B adenosine receptor reduces left ventricular dysfunction and ventricular arrhythmias 1 week after myocardial infarction in the rat model

Background Remodeling occurs after myocardial infarction (MI), leading to fibrosis, dysfunction, and ventricular tachycardias (VTs). Adenosine via the A 2B adenosine receptor (A 2B AdoR) has been implicated in promoting fibrosis. Objective To determine the effects of GS-6201, a potent antagonist of the A 2B AdoR, on arrhythmogenic and functional cardiac remodeling after MI. Methods Rats underwent ischemia-reperfusion MI and were randomized into 4 groups: control (treated with vehicle), angiotensin-converting enzyme inhibitor (treated with enalapril 1 day after MI), GS-6201-1d (treated with GS-6201 1 day after MI), GS-6201-1w (treated with GS-6201 administered 1 week after MI) . Echocardiography was performed at baseline and 1 and 5 weeks after MI. Optical mapping, VT inducibility, and histologic analysis were conducted at follow-up. Results Treatment with the angiotensin-converting enzyme inhibitor improved ejection fraction (57.8% ± 2.5% vs 43.3% ± 1.7% in control; P P P Conclusions Treatment with an A 2B AdoR antagonist at 1 week results in the improvement in cardiac function and decreased substrate for VT. The inhibition of fibrogenesis by A 2B AdoR antagonists may be a new target for the prevention of adverse remodeling after MI.