Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs
Oleg F. Sharifov, MD, PhD* ,*,
Vadim V. Fedorov, PhD*,
Galina G. Beloshapko, PhD*,
Alexey V. Glukhov, MS*,
Anna V. Yushmanova, PhD* and
Leonid V. Rosenshtraukh, PhD*
* Laboratory of Heart Electrophysiology, Cardiology Research Center, Moscow, Russia
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Figure 1 Tracings of the electrode array with main anatomic landmarks. Numbers indicate sites of unipolar electrodes. FWRA = free wall of right atrium; IVC = inferior vena cava; RAA = right atrial appendage; RPV = right pulmonary vein; SVC = superior vena cava.
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Figure 2 (A) Effects of sinus node artery perfusion with 1 to 2, 10, and 100 µmol/l (µmol/l) catecholamines at a flow rate of 1.2 ml/min for 3 min (left) and 9 ml/min for 1 min (right) on heart rate. "n" indicates the number of perfusions. All curves differ substantially from baseline. p < 0.05 for all individual comparisons. (B) Percentage of perfusions that induced at least one atrial tachyarrhythmia. *p < 0.05 vs. Tyrode's solution. **p < 0.05 vs. 1.2 ml/min.
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Figure 3 Catecholamine-mediated atrial fibrillation (A) and its prevention by atropine (B). The sinus node artery perfusion at 9 ml/min with 10 µmol/l (µm) adrenaline repeatedly induced atrial fibrillation in  25 s after the start of perfusion. With atropine, no tachyarrhythmic events were induced by adrenaline perfusion, despite the enhanced effect on heart rate. E1 and E2 = atrial bipolar electrograms; P2 = blood pressure recording; II = standard electrocardiographic lead II.
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Figure 4 Atrial fibrillation induced by 1 µmol/l acetylcholine (ACh) (A) and 0.1 µmol/l ACh and 2 µmol/l isoproterenol (B). In the control experiment, an ACh concentration of 1 µmol/l was the threshold that repeatedly induced atrial fibrillation (AF) in that dog. The perfusion onset led to sinus rhythm slowing. Seven seconds after the start of perfusion, the atrial premature beat triggered AF. The perfusion was immediately stopped, and the paroxysm lasted for 12 s. Perfusion with ACh and isoproterenol resulted in less sinus rhythm slowing, and the paroxysm arose from a stable and faster rhythm than that before perfusion. Notably, the ACh concentration used to induce AF was 10 times less than that without isoproterenol. This paroxysm started with some delay and lasted for 90 s (not shown). CL = cycle length; E1 and E2 = atrial bipolar electrograms; P2 = blood pressure recording; II = standard electrocardiographic lead II.
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Figure 5 Atrial fibrillation induced by 1 µmol/l acetylcholine. On the atrial unipolar electrogram at the top, A indicates atrial signal and V indicates ventricular signal. The impulses A to A5 are those in the subsequent maps. The impulses A and A1 are shown as isolated beats, and the impulses A2 to A5 are shown as consecutive cycles. Small squares indicate sites of unipolar electrodes; numbers indicate the activation time. Lines show isochrones. Arrows show the spread of excitation over the right atrium. This paroxysm started from a stable sinus rhythm with a cycle length (CL) of 384 ms. Beats A and A1 had a normal activation sequence similar to that in control (not shown). The earliest activation site was in the sinoatrial node region. The right atrium was activated for 45 ms. An atrial premature beat (A2) following beat A1 at a CL of 138 ms arose from the crista terminalis. In the free wall of right atrium, the conduction was blocked, and the impulse turned around an area of block counterclockwise. The area distal to the initial block was then activated retrogradely, and the impulse A3 re-entered the sites proximal to the initial block. Beats A4 and A5 were also re-entrant with a shortening revolution time. PV = pulmonary vein. Other abbreviations as in Figure 1.
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Figure 6 (A) The atrial fibrillation cycle length (AFCL) during the first 10 cycles of atrial fibrillation (AF) induced by acetylcholine (ACh) alone and ACh with isoproterenol (Iso). (B) The AFCL in different regions of the right atrium. *p < 0.05 vs. SVC, RPV, and IVC. **p < 0.001 vs. all regions. (C) The standard deviation (SD)-AFCL in different regions of the right atrium. Abbreviations as in Figure 1.
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