Metabolic therapy involves the administration of a substance normally found in the human body to enhance cellular reactions involved in the pathogenesis of disease. Myocardial ischaemia/reperfusion injury represents a leading cause of morbidity and mortality, also in cardiovascular disease. Therapeutic strategies aimed at limiting cardiomyocyte death during the postischaemic reperfusion and in the perioperative settings are nowadays extensively studied. Conceived originally as a dietary constituent (known as vitamin B13) only, it is now apparent that most orotic acid is synthesized in the human body where it arises as an intermediate in the biosynthetic pathway of pyrimidine nucleotides. Previous investigations in the heart suggest that orotate and its derivatives could be of significant clinical benefit in the treatment of heart disease. The present brief review is concerned with the current knowledge of the major effects of these compounds in both experimental and clinical cardiology. The potential mechanisms and biochemical pathways responsible for cardioprotection are highlighted.

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