Metabolic and functional effects of purines in the heart

This thesis discusses metabolism and functional effects of purine nucleosides and oxypurines in the heart. The study is mainly limited to the nucleosides adenosine and inosine and the oxypurines: hypoxanthine, xanthine and urate, all adenine-nucleotide catabolites. It is confined to effects in mammals, especially rats, pigs, and humans. Within certain disciplines, various aspects of the purines have been explored extensively. Neuropharmacologists have researched the adenosine receptors. Purine analogues have been synthesized for the treatment of neoplasms and virus infections. The erythrocyte membrane has been used to evaluate the transport across membranes. The study of some metabolic diseases and renal calculus formation provided knowledge of normal purine metabolism. There are several reasons why an important part of this thesis is devoted to adenosine. The knowledge of adenosine-induced effects is the most detailed. Adenosine has stronger effects than, for example, inosine. There are indications for the involvement of adenosine in the effects of other nucleosides. Purines are important in cardiac research. Ischemia rapidly elevates purine concentrations. This elevation may serve as a diagnostic tool for the quantification of ischemia. The difference in enzyme activities between various species causes concentration differences. Both endogenous and exogenous nucleosides affect hemodynamics and metabolism. Several drugs modify purine metabolism or purine induced effects. Purinergic receptors mediate effects of the nucleosides. The effects in vivo and in isolated organs are different, as nucleosides have both direct effects on cardiac cells, and indirect through the autonomic system. The objective of this thesis is the evaluation of purine function and metabolism in the heart, in the hope that this knowledge is useful for extended basic research and for the treatment of the cardiological patient. Transport and metabolism are discussed to demonstrate what concentrations may be expected and which conditions alter purine levels. The functional effects of the nucleosides in the heart are shown and their modification by the autonomic system. Finally, effects in pathological hearts, interaction with drugs, and some clinical applications are presented