INTERPLAY BETWEEN MILRINONE AND ADENOSINE IN THE INHIBITION OF HUMAN PLATELET RESPONSE

1. In this study, we investigated the influence of the inotropic agent and coronary vasodilator milrinone on platelet aggregation and intrac ellular levels of 3',5' cyclic adenosine monophosphate (cAMP) in human platelet-rich plasma (PRP) and whole blood (WB). Furthermore, we eval uated the influence of milrinone on the effects of adenosine, which re duces the platelet aggregation through an elevation of intraplatelet c AMP levels. 2. Milrinone decreased the platelet aggregation in respons e to agonists in both PRP and WB. A dose-dependent increase of intrapl atelet cAMP levels was demonstrated: this result is in accordance with an effect on platelet phosphodiesterases. 3. Milrinone at low concent ration and adenosine exerted additive effects on platelet aggregation and intraplatelet cAMP levels. 4. An interplay between milrinone and a denosine was shown in WB. Furthermore, dipyridamole, which prevents th e uptake of endogenous adenosine, markedly enhanced the milrinone anti aggregating effect, whereas the adenosine receptor blocker, theophylli ne, decreased it. 5. The present data provide evidence that milrinone modulates the platelet function through an influence on intraplatelet levels of cAMP and it is able to interplay with substances stimulating adenylyl cyclase. 6. The interplay between milrinone and adenosine in the inhibition of the human platelet function could be effective duri ng milrinone administration in the treatment of heart failure, when bl ood adenosine levels are significantly increased. These milrinone effe cts could be advantageous from a therapeutic point of view, since pati ents with heart failure are at risk of thrombosis and ischemic heart d isease. Copyright (C) 1996 Elsevier Science Inc.