Transient increase in release of adenosine during rapid cardiac pacing; transient effects on overdrive suppression of...

A study was designed to test the hypothesis that endogenous adenosine concentration may increase during episodes of rapid ventricular pacing and, by virtue of its negative chronotropic effects, contribute to the transient suppression of automaticity that follows the period of overdrive. Isolated, perfused, rat ventricular preparations were subjected to periods of 6.0 Hz overdrive stimulation while adenosine release, oxygen consumption, and subsequent suppression of automaticity were measured. At the end of a 1 min episode of overdrive oxygen consumption and adenosine release were significantly increased, and the initial beating rate after 1 min overdrive was suppressed. At the end of 10 min overdrive oxygen consumption was still increased but adenosine release had returned to control values. Suppression of automaticity after 10 min overdrive was similar to that after 1 min overdrive. The relative magnitude of suppression after 1 min overdrive was decreased by theophylline (10(-4) mol.litre-1), and increased by the adenosine deaminase inhibitor, EHNA (10(-5) mol.litre-1). Neither theophylline nor EHNA had any discernible influence on suppression after 10 min overdrive. It its therefore concluded that endogenous adenosine may contribute to the suppression of ventricular automaticity that follows a 1 min episode of overdrive, but because of the transient nature of the increase in adenosine during overdrive endogenous adenosine does not contribute to the suppression that follows prolonged overdrive.