Interaction between autonomic tone and the negative chronotropic effect of adenosine in humans

Prior studies have demonstrated that sympathetic tone may influence the effects of adenosine on His-Purkinje automaticity, and that enhanced vagal tone may influence its effects on the sinus node. However, the interaction between autonomic tone and the effects of adenosine on the sinus node in humans remains unknown. Therefore, this study was designed to investigate the interaction between different states of autonomic tone and the bradycardiac response of the sinus node to adenosine. In 11 patients without structural heart disease who underwent a clinically indicated electrophysiology procedure, the sinus cycle length was measured before and after a 12-mg bolus of adenosine in the baseline state, during an infusion of 2 mcg/min of isoproterenol, after the administration of 0.2 mg/kg of propranolol, and again after the administration of 0.04 mg/kg of atropine. Adenosine significantly lengthened the sinus cycle length in the baseline state (760 +/- 165 vs 909 +/- 188 ms, P < 0.05), during isoproterenol infusion (516 +/- 67 vs 766 +/- 146 ms, P < 0.05), after propranolol (850 +/- 153 vs 914 +/- 143 ms, P < 0.05) and after the combination of propranolol and atropine (662 +/- 76 vs 801 +/- 121 ms, P < 0.05). The degree of lengthening in sinus cycle length was significantly greater (P < 0.05) during isoproterenol infusion (253 +/- 157 ms, or 51% +/- 40%) than in the baseline state (149 +/- 85 ms, or 20% +/- 12%), after propranolol (68 +/- 53 ms, or 8% +/- 8%), and after propranolol and atropine (140 +/- 110 ms, or 21% +/- 18%). The negative chronotropic effect of adenosine is influenced by autonomic tone. The effect of adenosine on the sinus node is accentuated by beta-adrenergic stimulation and unaffected by beta-adrenergic blockade or combined beta-adrenergic and cholinergic blockade.