Abstract 12426: Long-term Inhibition of A2B Adenosine Receptor is Critical in Reducing Left Ventricular Remodeling and Dysfunction after Myocardial Infarction in Rat
We previously reported that GS-6201, an A2B adenosine receptor (ADOR) antagonist,effectively reduced MI-induced LV remodeling and dysfunction in a rat model suggesting that adenosine released during ischemia contributes to post-MI LV remodeling via activating A2B ADOR. The objective of the present study was to determine the role of adenosine on LV remodeling at different phases of post-ischemia/MI which was accomplished by a cross-over study design. One week after MI, animals were treated with either vehicle (Veh) or GS-6201 (GS, 30 mg/kg) via oral gavage once daily. At week 3 post-MI, 10 out of 18 rats in vehicle group were switched to GS (Veh→GS); similarly, 10 out of 20 rats receiving GS were switched to Veh (GS→Veh) and the treatments were continued for another 7 weeks. Sham group (n=10) was not subjected to MI or any treatment. The changes in LV geometry and function were assessed by serial echocardiography for 10 weeks. As shown in Figure 1, LV dysfunction developed in Veh treated animals. Treatment with GS throughout the study period significantly increased LV ejection fraction and fractional shortening, improved cardiac output and reduced LV volume as well as LV diameter in systole. However, when GS treatment was withdrawn at wk 3 post-MI, its beneficial effect was gradually reduced (Fig 1. A). On the other hand, a delayed treatment with GS, i.e. starting at 3 wk post-MI, prevented further deterioration of LV function (Fig 1. B) and remodeling in the subsequent weeks. In summary, a long-term inhibition of A2B adenosine receptor is required to maintain a sustained protection on MI-induced LV dysfunction and remodeling. In addition, GS was still efficacious when the treatment was initiated at a relatively advanced stage of LV remodeling following MI suggesting that adenosine plays an important role in all phases of post-MI remodeling.
- © 2013 by American Heart Association, Inc.