Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus each drug alone, in terms of ventricular function, infarct size reduction and angiogenesis. Myocardial ischemia was created in rodents and treated with adenosine, inosine or their combination. Results of experiments showed that the combination of both drugs significantly reduced infarct size and improved myocardial angiogenesis and ventricular function. The two compounds, while chemically similar, use different intracellular pathways, allowing for complementary biological activities without overlapping. The drug combination at specific 1？:？5 adenosine？:？inosine dose ratio demonstrated positive cardiologic effects, deserving further evaluation as an adjunct to reperfusion techniques during and after acute coronary syndrome. The association of adenosine and inosine may contribute to reduce myocardial infarction morbidity and mortality rates. 1. Introduction Adenosine has demonstrated cell-protective activity in animal and human models of ischemia reperfusion that involves the participation of all adenosine receptor subtypes [1, 2]. Adenosine also stimulates the production of vascular endothelial growth factor (VEGF) which promotes angiogenesis, especially during and immediately after acute ischemia [3–5]. Inosine is an inotropic agent without chronotropic effect that does not increase myocardial oxygen consumption [6–9]. It has also been demonstrated in experimental models cell-protective activities [10, 11]. Whereas the effects of adenosine are mediated by the combined function of the entire adenosine receptor family (A1, A2a, A2b, A3), no specific inosine receptor has been identified to date at the level of vascular and cardiac cells. Therefore, pathways supporting its effects remain uncertain and most of them are presumed to be energy restoration mechanisms [11]. A combination (mixture) of the two nucleosides adenosine and inosine at a specific 1？:？5 dose ratio has been found to synergistically enhance arterial vasodilation and be haemodynamically equivalent to adenosine optimal dose alone, using a dose of adenosine cut by 50%. Given, firstly, that ATP and energy nucleoside substrates depletion is a rapid process and the major cause of death in myocardial cells submitted to acute ischemic conditions, and,
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