Purine metabolism in the heart. Strategies for protection against myocardial ischaemia.

Adenosine has recently received much attention for the protection it provides against the deleterious effects of ischaemia reperfusion. Whenever the demand for oxygen exceeds its supply, adenosine triphosphate in myocytes is rapidly dephosphorylated to adenosine. Adenosine may then protect the myocardium against ischaemia-reperfusion damage. However, the accumulation of adenosine is limited by its rapid uptake and catabolism in the endothelium and in red blood cells. The strict compartmentalization of the enzyme pathways involved in the metabolism of adenosine, e.g. adenosine production by myocytes, its pharmacological action in the interstitium, its catabolism in the endothelium and in red blood cells, and its carrier-mediated transport across membranes, provides a unique target for pharmacological interventions. Blockade of adenosine uptake may indeed result in prolonged adenosine accumulation specifically in those regions of the heart where it is produced. In recent years considerable evidence has been gathered on the adenosine-mediated cardioprotective actions of nucleoside transport inhibitors.