Purine Nucleotide Precursors in Preventing Myocardial Ischemia-Reperfusion Injury

Changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage are caused by disruptions in ATP supply and/or demand in the heart. These disruptions may affect myocardial energetics and, consequently, cardiac function and mechanics. Increased cardiac inorganic phosphate levels and decreased myocardial ATP levels are the outcomes of this decrease in purine nucleotide levels. Both modifications can immediately affect cellular mechanical work and tension development. Depletion of cardiac nucleotides and compromised myocardial mechanical function are linked to both acute myocardial ischemia and decompensatory remodelling of the myocardium in heart failure. Theoretically, in both acute ischemia and chronic high-demand situations associated with the development of heart failure, an imbalance in the breakdown, salvage, and synthesis of purine nucleotides results in a net loss of purine nucleotides. It was found that the use of nucleotide precursors can be a potentially effective approach to diminishing ischemia-reperfusion damage. The scope of this article is to review knowledge of the effect of purine nucleotide precursors such as D-ribose, AICAR, inosine, hypoxanthine, and adenine on myocardial ischemia-reperfusion injury and highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with ischemia-reperfusion injury by these molecules.