Interaction of adenosine and prostacyclin in coronary flow regulation after myocardial ischemia

The role of adenosine and prostacyclin in post-ischemic vasodilation was in vestigated using a model of sequential perfusion of two isolated hearts. Tw o guinea pig hearts were sequentially perfused (10 ml/min) without (control , n = 4) or with preceding 10-min ischemia (n = 6) of Heart I. Under contro l conditions no hemodynamic changes were observed in Heart II during sequen tial perfusion. After 10 min of ischemia of Heart I coronary perfusion pres sure decreased by 23% in Heart IT at the onset of sequential perfusion. Ade nosine A(1) and A(2) receptor antagonists 1,3-dipropyl-8-cyclopentylxanthin e (DPCPX) (2 mu M) and 3,7-dimethyl-1-propargylxanthine (DMPX) (20 mu M) in fused simultaneously inhibited this decrease in coronary perfusion pressure by 74%, whereas indomethacin (5 mu M) had no effect. DPCPX, DMPX and indom ethacin in combination induced a significant increase in coronary perfusion pressure. Adenosine release (HPLC) into the coronary effluent after ischem ia was significantly enhanced in the presence of indomethacin. These result s suggest that after myocardial ischemia prostacyclin has an inhibitory eff ect on adenosine release. (C) 1999 Elsevier Science B.V. All rights reserve d.