ARA Technology
ARAs show promise of becoming the first class of “preconditioning mimetic” agents. ARAs work in a highly site- and event-specific manner, enhancing the localized release of adenosine exclusively in ischemic tissue while avoiding the systemic complications of adenosine.
Adenosine is a naturally occurring, physiologically active molecule that is produced throughout the body in response to multiple types of cellular stress that include but are not limited to ischemia and tissue hypoxia. Endogenous acts locally to regulate a variety of cell functions and/or physiological responses (e.g. heart rhythm, blood vessel tone, wakefulness, urine production etc.). Adenosine mediates its varied effects by activating specific subtypes of adenosine receptors that are constituents of the cell membrane. Currently adenosine is used intravenously in cardiology settings to reduce the normal flow of the electrical impulses through the atrio-ventricular (AV) node of the heart to treat certain types of arrhythmias. There continues to be an increasing appreciation of endogenous adenosine-mediated cardioprotection:
- Adenosine targets a very broad spectrum of the pathophysiology of ischemia/reperfusion injury. It not only targets broad spectrum of cell types and inflammatory mediators, but important cell signaling pathways as well.
- New knowledge of the phenomena of ischemic preconditioning and postconditioning define an extended range of clinical relevance of adenosine mediated cardioprotection.
Adenosine regulating agents exploit the growing scientific appreciation of adenosine’s natural role in mitigating ischemia/reperfusion injury. ARAs possess advantages over systemic adenosine in that they amplify the body’s own broad-spectrum response to ischemia/reperfusion through the localized release of adenosine exclusively in ischemic tissue. Preclinical studies show that ARAs reduce granulocyte content in ischemic myocardium, improve both epicardial and endocardial blood flow selectively in ischemic tissue, and improve ventricular function during coronary artery occlusion. Numerous preclinical studies show that ARAs increase endogenous adenosine concentrations in an event-specific and site-specific fashion, remaining pharmacologically silent in the absence of net ATP breakdown with no disturbances in heart rate or blood pressure.
The protection that ARAs convey is not limited to heart tissue during CABG and provides the protective benefits of ARA technology in other organs and conditions such as lung, intestine, sepsis, CAD, brain and heart transplants when affected tissues are confronted with ischemia/reperfusion insult.