Effects of adenosine on electrical activity of isolated guinea pig hearts

Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.