Synergistic action of atrial dilation and sodium channel blockade on conduction in rabbit atria.
BACKGROUND
The aim of this study was to investigate the interaction of atrial dilation and blockade of the rapid sodium channel on atrial conduction and degree of anisotropy.


RESULTS
The right atrium was acutely dilated by increasing intra-atrial pressure from 2 to 9 cm H2O in 14 isolated rabbit hearts. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium during pacing from four different directions at intervals of 240 and 140 msec. In nondilated atria, 0.5 and 1.0 mg/L of the use-dependent INa blocker flecainide prolonged the total conduction time under the mapping electrode by 15% to 75%. In dilated atria, flecainide depressed conduction by 24% to 89% (P < 0.05). The incidence of intra-atrial conduction block increased from 0.6%-0.8% to 3.3%-7.2% in nondilated atria and from 3.9%-4.6% to 13%-21% in dilated atria (P < 0.05). The direction of activation relative to the crista terminalis and major pectinate muscles was of major importance for occurrence of conduction block. During rapid pacing, the degree of anisotropy in conduction increased by the combination of atrial dilation and flecainide (1.0 mg/L) from 1.7 +/- 0.1 to 2.2 +/- 0.4 (P < 0.05). The effects of dilation and flecainide on conduction were clearly synergistic. The effect of flecainide on the atrial refractory period also was enhanced by atrial dilation.


CONCLUSIONS
In dilated atria, blockade of the rapid sodium channels caused a higher degree of local conduction delay and intra-atrial conduction block than in nondilated atria.
Eijsbouts
Sabine C M
SC
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Houben
Richard P M
RP
Blaauw
Yuri
Y
Schotten
Ulrich
U
Allessie
Maurits A
MA
D000704:Analysis of Variance; D000818:Animals; D016880:Anisotropy; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004108:Dilatation, Pathologic; D022062:Electrophysiologic Techniques, Cardiac; D005424:Flecainide / Q000494:pharmacology*; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D011817:Rabbits; D015222:Sodium Channels
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D005424:Flecainide