Nucleoside transport inhibition for cardioprotection: New perspectives for the clinic

In this review the role of adenosine, produced in the myocardium in response to ischemia, as a “natural defense” system is briefly summarized. In contrast with exogenous adenosine or adenosine agonists, interference with adenosine metabolism will restrict the action of endogenous adenosine to when and where it is produced (site and event specificity). In this respect, Nucleoside transport inhibition seems to be the preferred strategy because of a dual effect, namely, attenuation of catabolism during ischemia and delay of the washout upon reperfusion. In a variety of experimental studies in animals, nucleoside transport inhibition has been documented to afford marked cardioprotection. Failure in humans thus far may be due to the shortcomings of the few existing drugs. The development of draflazine, a new transport inhibitor with a more appropriate pharmacokinetic profile may open new perspectives for therapy based on this concept. © 1993 Wiley-Liss, Inc.