Innovative therapeutic approaches for the treatment of myocardial ischemia and angina

Abstract

Cardiac energy metabolism is complex and has three main components: 1. Substrate utilisation, 2 Oxydative phosphorilation and 3. Transfer of high energy phosphates. Substrate utilization involves the cellular uptake of free fatty acids, glucose and amino acids, their breakdown by beta-oxidation and glycolysis, and the entry of Acetyl Coenzyme A into the Krebs cycle. Oxidative phosphorylation involves the production of energy by the mitochondrial respiratory chain and the production of high-energy phosphates. Until recent it was not known that it was possible to delimitate the infarct size through therapeutic interventions. Likely, the improvement to understand the mechanisms of cellular survivor occurs in that year, when Murry et al. discovered an intrinsic mechanism of myocardial protection, which they denominated as ischemic preconditioning. In that experiment, it was observed that four cycles of five minutes of ischemia, with intermittent reperfusion, before 40 min of ischemia period, resulted in reduction of 75% of the infarct size. Also, it was demonstrated by these researches that this protection it was not resulted by collateral overture and that protective effect of the ischemic preconditioning was abolished in the presence of prolonged ischemia, with duration of 3 h. Two phenomenons, the walk-through angina and the warm up phenomenon could represent a clinical manifestation of preconditioning. The phenomenon of walk-through angina was first related in the end of century XVIII in a patient that developed angina during the effort, but experimented the paradox disappearing of the pain with the exercise continuation. The exact molecular mechanisms involved in ischemic preconditioning are not fully elucidated. Therefore, due to the high prevalence of risk factors to cardiovascular diseases and the high morbidity and mortality associated with coronary artery disease, there is a needed to understand even better the cardiac metabolism during ischemia and the strategies to reduce the consequences of the ischemia, to preserve the viability of the ischemic myocardium.