Effects of adenosine and adenosine 5'-triphosphate on ventricular escape rhythm in the canine heart

The effects of adenosine and adenosine 5'-triphosphate (ATP) on ventricular escape rhythms were studied in 16 closed chest dogs after electroablation of the His bundle region. All dogs exhibited complete atrioventricular (AV) block and stable ventricular escape rhythm with a mean cycle length of 1,210 +/- 80 ms and a QRS width of 91 +/- 5 ms. Physiologic AV sequential pacing was operative during experiments and was interrupted for rapid (less than or equal to 1 second) administration of either adenosine or ATP (3 mumol/kg) into the right atrium. Adenosine and ATP effectively depressed ventricular escape rhythms in a similar manner both qualitatively and quantitatively (cycle length from 1,210 +/- 80 to 1,764 +/- 132 ms and from 1,274 +/- 84 to 2,000 +/- 150 ms, respectively; each p less than 0.01). These effects were not significantly altered by either physostigmine (an acetylcholinesterase inhibitor) or atropine (a muscarinic cholinergic blocker), but were slightly attenuated by propranolol (a beta-adrenoceptor blocker). In the presence of autonomic blockade, the adenosine transport blocker dipyridamole markedly enhanced the depressant effects of adenosine and ATP. The adenosine competitive antagonist aminophylline reversed the action of dipyridamole. Thus, both adenosine and ATP depress ventricular escape rhythms in vivo, independent of the autonomic nervous system. Moreover, the effects of ATP can be accounted for in large part by its rapid breakdown to adenosine.