To answer some of the as yet unresolved questions about the formation, metabolism, and release of purine catabolites in hypoxic myocardium, we compared their release from isolated rabbit hearts during hypoperfusion, anoxia, and after ischemia, with and without nucleoside-transport inhibition. Results provide evidence to suggest the following. Besides the supply-to-demand ratio for O2, other factors may affect the formation of adenosine. The myocyte is the major source of purine catabolites. Adenosine is not produced within the myocyte. Once in the interstitium, adenosine is (largely) taken up in the endothelial cells, where it is catabolized to inosine and hypoxanthine and released that way into the lumen. Some of the adenosine can reach the lumen unchanged through clefts. Nucleoside transport inhibition prevents the escape through the endothelial cells and thus the formation and release of inosine and hypoxanthine. As a consequence, more adenosine will accumulate in the interstitium and more will reach the lumen through the clefts. The pathway, as proposed, explains the long known paradox of increased extracellular levels of adenosine after inhibition of nucleoside transport.

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