title: 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.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210-1218, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lou
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Glukhov
authors.forename: Brian
authors.initials: B
authors.lastname: Hansen
authors.forename: Lori
authors.initials: L
authors.lastname: Hage
authors.forename: Pedro
authors.initials: P
authors.lastname: Vargas-Pinto
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001919:Bradycardia / Q000188:drug therapy* / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006327:Heart Block / Q000139:chemically induced* / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D012849:Sinoatrial Node / Q000187:drug effects* / Q000503:physiopathology*; D019265:Spectroscopy, Near-Infrared; D013610:Tachycardia / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000241:Adenosine