Tachy-brady arrhythmias: the critical role of adenosine-induced sinoatrial conduction block in post-tachycardia pauses.

Abstract

BACKGROUND:

In patients with sinoatrial nodal (SAN) dysfunction, atrial pauses lasting several seconds may follow rapid atrial pacing or paroxysmal tachycardia (tachy-brady arrhythmias). Clinical studies suggest that adenosine may play an important role in SAN dysfunction, but the mechanism remains unclear.

OBJECTIVE:

To define the mechanism of SAN dysfunction induced by the combination of adenosine and tachycardia.

METHODS:

We studied the mechanism of SAN dysfunction produced by a combination of adenosine and rapid atrial pacing in isolated coronary-perfused canine atrial preparations by using high-resolution optical mapping (n = 9). Sinus cycle length and sinoatrial conduction time (SACT) were measured during adenosine (1-100 μM) and DPCPX (1 μM; A1 receptor antagonist; n = 7) perfusion. Sinoatrial node recovery time was measured after 1 minute of "slow" pacing (3.3 Hz) or tachypacing (7-9 Hz).

RESULTS:

Adenosine significantly increased sinus cycle length (477 ± 62 ms vs 778 ± 114 ms; P<.01) and SACT during sinus rhythm (41 ± 11 ms vs 86 ± 16 ms; P<.01) in a dose-dependent manner. Adenosine dramatically affected SACT of the first SAN beat after tachypacing (41 ± 5 ms vs 221 ± 98 ms; P<.01). Moreover, at high concentrations of adenosine (10-100 μM), termination of tachypacing or atrial flutter/fibrillation produced atrial pauses of 4.2 ± 3.4 seconds (n = 5) owing to conduction block between the SAN and the atria, despite a stable SAN intrinsic rate. Conduction block was preferentially related to depressed excitability in SAN conduction pathways. Adenosine-induced changes were reversible on washout or DPCPX treatment.

CONCLUSIONS:

These data directly demonstrate that adenosine contributes to post-tachycardia atrial pauses through SAN exit block rather than slowed pacemaker automaticity. Thus, these data suggest an important modulatory role of adenosine in tachy-brady syndrome.

• Authors: Qing Lou, Alexey V Glukhov, Brian Hansen, Lori Hage, Pedro Vargas-Pinto, George E Billman, Cynthia A Carnes, Vadim V Fedorov
• Journal: Heart rhythm (Heart Rhythm) Vol. 10 Issue 1 Pg. 110-8 (Jan 2013) ISSN: 1556-3871 [Electronic] United States
• PMID: 22985657 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adenosine

Topics

• Action Potentials (drug effects)
• Adenosine (pharmacology)
• Analysis of Variance
• Animals
• Bradycardia (drug therapy, physiopathology)
• Cardiac Pacing, Artificial
• Dogs
• Dose-Response Relationship, Drug
• Heart Block (chemically induced, physiopathology)
• Heart Conduction System (drug effects, physiopathology)
• Sinoatrial Node (drug effects, physiopathology)
• Spectroscopy, Near-Infrared
• Tachycardia (drug therapy, physiopathology)