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 using high-resolution optical mapping (n=9). Sinus cycle length (SCL) and sinoatrial conduction time (SACT) were measured during adenosine (1–100μM) and 1μM DPCPX (A1 receptor antagonist, n=7) perfusion. Sinoatrial node recovery time was measured after one minute of “slow” pacing (3.3Hz) or tachypacing (7–9Hz). Results Adenosine significantly increased SCL (477±62 vs. 778±114 ms, p<0.01), and SACT during sinus rhythm (41±11 vs. 86±16 ms, p<0.01) dose-dependently. Adenosine dramatically affected SACT of the first SAN beat after tachypacing (41±5 vs. 221±98ms, p<0.01). Moreover, at high concentrations of adenosine (10–100μM), termination of tachypacing or atrial flutter/fibrillation produced atrial pauses of 4.2±3.4 seconds (n=5) due to conduction block between the SAN and atria, despite a stable SAN intrinsic rate. Conduction block was preferentially related to depressed excitability in SAN conduction pathways. Adenosine-induced changes were reversible upon 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.

Upregulation of Adenosine A1 Receptors Facilitates Sinoatrial Node Dysfunction in Chronic Canine Heart Failure by Exacerbating Nodal Conduction Abnormalities Revealed by Novel Dual-Sided Intramural Optical Mapping

“…Coronary-perfused canine SAN-atrial preparations 14-17 (n=10 HF, Figure 1A) were immobilized by 10-20μM blebbistatin, 18 and stained by di-4-ANBDQBS (10-40μM). 15, 17 Adenosine (1, 10 and 100μM), non-selective adenosine receptor blocker theophylline (50μM, n=4), and a selective A1R blocker DPCPX 19 (1μM, n=4) were applied to the perfusate.…”

“…15, 17 Adenosine (1, 10 and 100μM), non-selective adenosine receptor blocker theophylline (50μM, n=4), and a selective A1R blocker DPCPX 19 (1μM, n=4) were applied to the perfusate. The detailed sequential drug treatments for each canine SAN preparation are illustrated in Supplemental Table 2.…”

“…17 SAN conduction time (SACT) was measured during sinus rhythm (SACT sr , Figure 2A) as well as the first post-pacing SAN beat (SACT ppb , Figure 3A). Indirect SNRT (SNRT i ) and direct SNRT (or SNRT d ) 21 were measured (Figure 3A).…”

“…Functional results from HF preparations were compared with the results from seven control SAN experiments, which were conducted in our previous study with the same protocols. 17 For more details, please see the online Data Supplement.…”

Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice

“…We next measured corrected SAN recovery times (cSNRTs) (26) in response to different pacing rates in WT and KO SANs. cSNRT is a common clinical test to investigate SAN dysfunction (27) and is defined as the period of quiescence after rapid pacing, normalized to the pacing rate (11,26). In both WT and KO, we found that cSNRT was directly proportional to the rate of stimulation (Fig.…”