Adenosine and the Cardiovascular System

Allison B. Reiss; David Grossfeld; Lora J. Kasselman; Heather A. Renna; Nicholas A. Vernice; Wendy Drewes; Justin Konig; Steven E. Carsons; Joshua DeLeon


Am J Cardiovasc Drugs. 2019;19(5):449-464. 

In This Article


Adenosine is an endogenous purine nucleoside with an extremely short half-life that functions as an extracellular signaling molecule. Under physiological conditions, adenosine is present at very low concentrations. However, conditions of hypoxia, inflammation and cellular stress lead to generation of this molecule and a consequent rise in interstitial levels, conferring protection against tissue damage. Among its cardioprotective effects are induction of coronary artery vasodilation, reduction of myocardial oxygen demand and anti-platelet activity.

Adenosine and related compounds are commonly used vasodilators for determination of coronary fractional flow reserve in myocardial perfusion imaging for the detection of obstructive coronary artery disease. It has potent negative chronotropic (slows sinus rate) and dromotropic (slows AV node conduction) effects on the heart. It decreases peripheral resistance and arterial pressure. It is eliminated by cellular uptake and metabolism (deamination and phosphorylation).

In rodents and other animal models, adenosine enhances post-ischemic functional recovery of the myocardium with decreased infarct size. While highly effective in these models of reperfusion, it has failed to achieve dramatic clinical benefits in human studies. Further, the exact pathways and receptors involved in cardioprotection remain unresolved even though selective agonists and antagonists have been developed for each adenosine receptor subtype. Although the adenosine receptors and particularly the A2A receptor are still considered promising drug targets for the heart, results thus far have been disappointing. UK-432,097, an A2A agonist developed by Pfizer, was tested for use in asthma and chronic obstructive pulmonary disease, but failed in clinical trials due to lack of efficacy and is not available for use in humans.[202,207,208] While new compounds and delivery techniques are in development, the future is uncertain.[209–212]