Abstract 18400: Intravenous Ranolazine Relieves Ischemia by Increasing Myocardial Adenosine Levels

Background: The mechanism by which ranolazine (RAN) reduces stress-induced myocardial ischemia is not fully understood. Hypothesis: RAN relieves myocardial ischemia through the cardioprotective effects of adenosine(ADEN). Methods: Non-flow limiting stenosis was created in the LAD in 17 open-chest dogs. We compared regional myocardial function (echo radial strain) and perfusion (myocardial blood volume), and regional ADEN level in the absence and presence of intravenous RAN at rest and during dobutamine stress. ADEN level from the supernatant of murine cardiac endothelial cells subjected to oxygen glucose deprivation to stimulate ischemia before and after addition of RAN was also measured alone (n=5) and in the presence of the cytosolic-5’-nucleotidase inhibitor thymidine 5’ monophosphate (TMP) (n=6) and the ecto-adenosine deaminase inhibitor pentostatin (n=4). ADEN is produced from 5’AMP via cytosolic-5’-nucleotidase and is converted to inosine via ecto-adenosine deaminase. Results: In the presence of RAN...