[Cardiac effects of adenosine. Mechanism of action, pathophysiologic and clinical significance].

Adenosine has a negative inotropic effect in cardiac atrial preparations ("direct" negative inotropic effect). This effect is probably due to an activation of a potassium outward current which shortens the action potential duration and hence reduces the force of contraction. A pertussis toxin-sensitive N-protein is involved in the signal transduction from the adenosine receptor to atrial potassium channels. In ventricular cardiac preparations adenosine has no negative or even a weak positive inotropic effect, but it reduces the force of contraction in the presence of cAMP-increasing agents such as isoprenaline ("indirect" negative intropic effect). This effect is due to an inhibition of the slow Ca2+ inward current which has previously been enhanced by an increase in the cellular cAMP content. This "indirect" negative inotropic effect of adenosine is also present in the human heart. Since increased amounts of adenosine are released during cardiac stimulation via beta-adrenoceptors, the "indirect" effect might protect the heart against excessive stimulation by catecholamines. In addition, adenosine has negative chronotropic actions and prolongs AV conduction by an activation of potassium channels or an inhibition of the slow Ca2+ inward current (AV node). Cardiac bradyarrhythmias in hypoxia have been attributed to an increased formation and release of adenosine. Furthermore, adenosine has been shown to terminate supraventricular tachycardias involving the AV node. Since it has a very short duration of action it might prove safe and hence advantageous to conventional therapy in the treatment of supraventricular tachycardias.