EFFECTS OF ADENOSINE ON ATRIAL REFRACTORINESS AND ARRHYTHMIAS

Objective: Transient atrial fibrillation is sometimes observed following adenosine administration and adenosine is known to shorten atrial action potential duration and refractory period. This study was designed to characterise the dose-response relationship of adenosine on these variables relative to arrhythmia induction with single atrial premature stimuli. The effects of adenosine during sustained atrial flutter were also determined. Methods: Intravenous bolus doses of adenosine were given to pentobarbitone anaesthetised dogs following cervical vagotomy and autonomic blockade with atropine and nadolol. Monophasic action potential catheter recordings were obtained from the right atrium and a programmable stimulator was used for pacing. Results: Placebo had no effect on monophasic action potential duration (MAPD) or atrial effective refractory period (ERP) and no arrhythmias were observed. Adenosine (0.1-1.0 mg.kg(-1)) produced dose related decreases in MAPD and ERP and transient atrial fibrillation (5-122 s) was repeatedly and reproducibly induced in 12 dogs. In six dogs, intravenous dipyridamole (0.25 mg.kg(-1)) enhanced the effects of adenosine on MAPD and ERP and increased the incidence of atrial fibrillation. In another six dogs, 8-sulphophenyltheophylline (5.0 mg.kg(-1), intravenously) markedly blunted the effects of adenosine, and atrial fibrillation could no longer be induced by premature stimuli. In a separate series of experiments the effects of adenosine were evaluated in seven dogs in which sustained atrial flutter could reproducibly be induced by rapid atrial pacing. Administration of placebo never caused termination of the arrhythmia, whereas intravenous boluses of adenosine (0.1-1.0 mg.kg(-1)) decreased and produced variation in atrial flutter cycle length, and then terminated the arrhythmia in all cases. These effects of adenosine were also enhanced by dipyridamole and antagonised by 8-sulphophenyltheophylline. Conclusions: Adenosine produces a receptor mediated shortening of monophasic action potential duration and refractoriness which increases vulnerability to transient atrial arrhythmias. During sustained atrial flutter, these effects may also contribute to destabilisation and termination of the arrhythmia.