ACADESINE - PROTOTYPE ADENOSINE REGULATING AGENT FOR TREATING MYOCARDIAL ISCHEMIA-REPERFUSION INJURY

Acadesine is an adenosine regulating agent currently being developed for treatment of ischemia-reperfusion injury in the setting of cardiac surgery. While the cardioprotective effects of adenosine are well recognized, the intrinsic hemodynamic and cardiac effects of adenosine limit its potential usefulness as a therapeutic agent. In contrast, acadesine has been shown to elevate endogenous levels of adenosine during periods of ischemia without exhibiting systemic hemodynamic actions. The site-specific and event-specific mechanism of action thus provides cardioprotection without the adverse sequelae commonly observed with adenosine. This review describes the pertinent literature which establishes acadesine's action as an adenosine regulating agent, and discusses past and recent studies which focus on the cardioprotective actions of acadesine. These studies include in vitro and in vivo models of regional and global ischemia, and models of cardiac surgery. Aspects of dose-response, timing of administration, and pharmacokinetics of acadesine are described which reconcile prior controversy regarding acadesine's cardioprotective actions. These studies, taken together, demonstrate that acadesine is the prototype of a new class of adenosine regulating agents useful as therapy for cardiac ischemia.