979-31 Intravenous Infusion of ATP Increases Coronary Blood Flow and Improves Ischemia via Elevation of Myocardial Adenosine Levels due to Degradation of ATP

Abstract

Adenosine is known to be cardioprotective for the ischemic heart, however, an intravenous administration of adenosine can not increase coronary blood flow (CBF) because of its rapid degradation. To test if an intravenous ATP administration is timely degraded to adenosine at the heart, we measured CBF of the left anterior descending coronary artery and coronary arteriovenous differences of adenosine concentration (Ado) in the canine hearts. Infusions of ATP (5, 10, 20, and 40 μg/kg/min) into the systemic vein increased Ado from 7 ± 4 to 19 ± 7, 38 ± 7, 68 ± 11 and 112 ± 15 pmol/ml, although ATP, ADP and AMP concentrations in the coronary venous blood were not increased. An intravenous infusions of ATP increased CBF from 93 ± 5 to 127 ± 6, 149 ± 5, 168 ± 78 and 195 ± 6 ml/100 g/min, which was blunted by 8-sulfophenyltheophylline. Aortic pressure was decreased by 12 ± 5 mmHg from 107 ± 5 mmHg during 40 μg/kg/min of ATP infusion. During ischemia due to reduction of perfusion pressure by 56 ± 4%, an intravenous infusion of 40 μg/kg/min of ATP increased CSF (56 ± 3 to 66 ± 5 ml/100 g/min) with increased fractional shortening (9 ± 2 vs 14 ± 3) and lactate extraction ratio (-34 ± 5 vs. -17 ± 6%). We conclude that an intravenous administration of ATP can elevate myocardial adenosine levels, and improve myocardial contractile and metabolic function in the ischemic heart. Intravenous ATP administration may be promising for cardioprotection in the patients with acute ischemic heart diseases.