Electrophysiologic Properties and Antiarrhythmic Effects of Adenosine and Adenosine Triphosphate

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Adenosine and its related compound, adenosine 54′-triphosphate (ATP), are endogenous nucleosides with very short half-life, found in human cells. They are known to have both proarrhythmic and antiarrhythmic effects on the electrophysiologic properties of cardiac tissue. In 1929, Drury and Szent-Gyorgyi were the first to report specific electrophysiologic effects of adenosine on cardiomyocytes and its relaxing effects on smooth muscle cells of coronary arteries [1]. It was not until the last decade, when several valuable studies considerably increased our understanding of the effects of endogenous and exogenous adenosine and its related compound, ATP on the heart. The coronary vasodilatory effect of adenosine led to its rapidly growing clinical utility to assess coronary reserve during myocardial perfusion imaging. By its coronary vasodilatory effect, adenosine increases myocardial oxygen supply and by decreasing myocardial contractility, antagonizing effects of catecholamines, and depressing automaticity and conduction within the sinus and atrioventricular nodes [2], it reduces myocardial oxygen demand. The electrophysiologic effects of adenosine include depression of sinus node and Purkinje fiber automaticity, slowing of atrioventricular nodal (AV) conduction, shortening and hyperpolarization of the atrial action potential, and antagonism of the effects of beta-adrenergic agonists on atrial and ventricular myocardium [3-5]. Because of safety, short half-life and its potent electrophysiologic effects it has been increasingly used in clinical practice for diagnosis and treatment of a variety of cardiac arrhythmias. The ability of adenosine to cause transient AV nodal block in patients with paroxysmal supraventricular tachycardia has led to the suggestion that, in addition to its therapeutic role, it may be useful for distinguishing supraventricular tachycardias dependant upon AV nodal conduction (AV nodal reentrant and AV reciprocating tachycardias) from those that are not [6-9]. It is generally thought that atrial tachycardias typically to not termiante with administration of adenosine, but recent reports indicate that adenosine transiently suppresses automatic atrial tachycardia, may terminate sinus node reentrant tachycardia, atrial tachycardia related to triggered activity and may or may not terminate intra-atrial reentry [6,9-15]. As expected, because adenosine shortens atrial action potential and perhaps atrial refractory period [16], it may shorten atrial flutter cycle length [17], and may even facilitate degenration of atrial flutter to fibrillation. Through the last decade, adenosine, has been found to be very useful in differentiating the broad complex tachycardias by either terminating supraventricular tachycardias or inducing a transient high degree AV nodal block, thereby, unmasking atrial arrhythmias. It has also been used to detect sinus node dysfunction in patients with sick sinus syndrome. Because of its transient potent AV nodal blockade, and little or no effect on typical accessory pathway function, latent pre-excitation may be identified. This has been used to identify functioning latent pre-excitation and to evaluate success of surgical or radio-frequency catheter ablation of accessory pathways. By and large, adenosine has no effect on ventricular tachycardia with the exception of a rare form called “adenosine-sensitive ventricular tachycardia” which is seen in structurally normal hearts and is thought to be related to cAMP mediated triggered activity [18].