EFFECTS OF ADENOSINE ON ATRIAL REFRACTORINESS AND ARRHYTHMIAS

Objective: Transient atrial fibrillation is sometimes observed followi ng adenosine administration and adenosine is known to shorten atrial a ction potential duration and refractory period. This study was designe d to characterise the dose-response relationship of adenosine on these variables relative to arrhythmia induction with single atrial prematu re stimuli. The effects of adenosine during sustained atrial flutter w ere also determined. Methods: Intravenous bolus doses of adenosine wer e given to pentobarbitone anaesthetised dogs following cervical vagoto my 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 n o effect on monophasic action potential duration (MAPD) or atrial effe ctive refractory period (ERP) and no arrhythmias were observed. Adenos ine (0.1-1.0 mg.kg(-1)) produced dose related decreases in MAPD and ER P and transient atrial fibrillation (5-122 s) was repeatedly and repro ducibly induced in 12 dogs. In six dogs, intravenous dipyridamole (0.2 5 mg.kg(-1)) enhanced the effects of adenosine on MAPD and ERP and inc reased the incidence of atrial fibrillation. In another six dogs, 8-su lphophenyltheophylline (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 a trial flutter could reproducibly be induced by rapid atrial pacing. Ad ministration of placebo never caused termination of the arrhythmia, wh ereas intravenous boluses of adenosine (0.1-1.0 mg.kg(-1)) decreased a nd produced variation in atrial flutter cycle length, and then termina ted 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 mo nophasic action potential duration and refractoriness which increases vulnerability to transient atrial arrhythmias. During sustained atrial flutter, these effects may also contribute to destabilisation and ter mination of the arrhythmia.