Multidrug prevention or therapy of ischemia-reperfusion injury of the heart-Mini-review

Restoration of blood flow to myocardium previously subjected to ischemia leads to ischemia/reperfusion injury due to oxidative stress. An increased production of toxic peroxynitrite, an enhanced phosphorylation and nitration/nitrosylation of myocyte contractile proteins and overactivation of matrix metalloproteinases −are only one of the several causes of heart damage. Multifactorial basis of ischemia/reperfusion injury demands the use of multiple pharmacological agents, inhibiting several pathways of cardiac injury. Nevertheless, the use of these drugs in their therapeutic doses, apart from their role in the treatment of pathological events, may also disturb physiological processes leading to numerous side-effects. Therefore current preclinical studies focuses on multidrug therapies in their low concentration. Synergistic or additive effect of low multidrug therapy inhibit pathological processes while maintaining the proper cell function and avoid alteration of physiological role of important functional proteins. This study provides information about multidrug strategies for the prevention/treatment of cardiac injury induced by oxidative stress.