Beta3-Adrenergic Receptor (β3-AR) Modulation Prior to and / or at the end of Sustained Ischaemia and / or Early Reperfusion May Prove to be a Valuable Cardioprotective Strategy

Abstract β3-AR activation contributes partly or may be solely responsible for ensuing cardiac damage in myocardial ischaemia or heart failure. This would largely depend on disease stage, severity, experimental model as well as drug specificities which should be considered when investigating β3-AR pharmacology for potential therapeutic applications. These conceptions largely contribute to the discrepancies of the subsequent role of β3-AR activation in the cardiovascular disease process. The β3-AR delivers a sustained intracellular signal because of its resistance to short term agonist promoted desensitization, making this receptor an ideal target for therapeutic intervention and in this manner protecting the heart from catecholamine overstimulation. The current communication highlights the importance of the cumulative effect of BRL (PerT) treatment, at the end stage of ischaemia as well as BRL (PostT) treatment, at the onset of reperfusion. This undoubtedly illustrate the significance of the end stage of ischaemia as well as the onset of reperfusion in the concept of ischaemia- reperfusion damage and the importance of the application of cardioprotective interventions at these time periods. Subsequently, if cardioprotective regimens are initiated during the late phase of ischaemia and continued into early reperfusion, it is likely that they will enhance protection, especially with longer durations of ischaemia.