Abstract 9272: Tachy-Brady Syndrome: The Critical Role of Adenosine-induced Sino-Atrial Conduction Block in Post-Tachycardia Pauses

Abstract

Introduction: In patients with sino-atrial nodal (SAN) dysfunction, long pauses lasting several seconds are often observed after rapid atrial pacing or paroxysmal tachycardia. Clinical studies suggest that adenosine may play an important role in the SAN dysfunction observed during metabolically compromised myocardial states, but the mechanism is unclear. Methods: We studied SAN dysfunction produced by a combination of adenosine and fast atrial pacing in an isolated coronary-perfused canine SAN preparation using high resolution optical mapping (n=7). Sinus cycle length (SCL) and direct SA conduction time (SACT) were measured during perfusion of Adenosine (1-100 µM, n=6), selective A1 receptor agonist CCPA (1-3 µM, n=3), and A1 antagonist DPCPX (1-3 µM, n=4). Corrected SAN recovery time (cSNRT) was measured after 1 minute of slow atrial pacing (3.3 Hz) and tachypacing (7-8 Hz). Results: Adenosine and CCPA significantly increased the SCL (469±66 vs. 674±175 ms, p=0.03), and SACT (44±11 vs. 94±15 ms, p<0.001) dose-dependently, as well as increasing cSNRT after slow atrial pacing (from 70±28 ms to 232±63 ms, p<0.001). Moreover, at high drug concentrations, termination of atrial tachypacing produced pauses up to 3.3±4.4 sec in 5 out 7 preparations due to complete conduction block between the SAN and atria, despite a stable SAN intrinsic rate (figure). Conduction block was preferentially related to depressed excitability in SAN conduction pathways. DPCPX restored the adenosine-induced changes of SCL, SACT and cSNRT back to control. Conclusion: These data directly demonstrate that post-tachycardia atrial pauses during adenosine perfusion resulted from depressed conduction between the SAN and atria (exit block) rather than from slowed pacemaker automaticity. Thus, these data suggest an important modulatory role for adenosine in tachy-brady syndrome: particularly in patients with ischemia or heart failure, conditions known to increase adenosine production.