Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs

Abstract

Background: Little is known about the relationship between intrinsic cardiac nerve activity (ICNA) and spontaneous arrhythmias in ambulatory animals.

Methods and results: We implanted radiotransmitters to record extrinsic cardiac nerve activity (ECNA; including stellate ganglion nerve activity and vagal nerve activity) and ICNA (including superior left ganglionated plexi nerve activity and ligament of Marshall nerve activity) in 6 ambulatory dogs. Intermittent rapid left atrial pacing was performed to induce paroxysmal atrial fibrillation or atrial tachycardia. The vast majority (94%) of ligament of Marshall nerve activity were preceded by or coactivated with ECNA (stellate ganglion nerve activity or vagal nerve activity), whereas 6% of episodes were activated alone without concomitant stellate ganglion nerve activity or vagal nerve activity. Paroxysmal atrial fibrillation and atrial tachycardia were invariably (100%) preceded (<5 seconds) by ICNA. Most paroxysmal atrial tachycardia events (89%) were preceded by ICNA and sympathovagal coactivation, whereas 11% were preceded by ICNA and stellate ganglion nerve activity-only activation. Most paroxysmal atrial fibrillation events were preceded only by ICNA (72%); the remaining 28% were preceded by ECNA and ICNA together. Complex fractionated atrial electrograms were observed during ICNA discharges that preceded the onset of paroxysmal atrial tachycardia and atrial fibrillation. Immunostaining confirmed the presence of both adrenergic and cholinergic nerve at ICNA sites.

Conclusions: There is a significant temporal relationship between ECNA and ICNA. However, ICNA can also activate alone. All paroxysmal atrial tachycardia and atrial fibrillation episodes were invariably preceded by ICNA. These findings suggest that ICNA (either alone or in collaboration with ECNA) is an invariable trigger of paroxysmal atrial tachyarrhythmias. ICNA might contaminate local atrial electrograms, resulting in complex fractionated atrial electrogram-like activity.

Figure 1

Recording sites and the study protocol. A, Ligament of Marshall (LOM) and superior left ganglionated plexi (SLGP). The LOM originates from coronary sinus and connects to left superior pulmonary vein (LSPV). SLGP is located between left atrial appendage (LAA) and LSPV. B, Left stellate ganglion. C, Superior cardiac branch of the left vagal nerve. D, Diagram of study protocol. LOM, ligament of Marshall; LSPV, left superior pulmonary vein; LIPV, left inferior pulmonary vein; SLGP, superior left ganglionated plexi; PA, pulmonary artery; LAA, left atrial appendage

Figure 2

Examples of intrinsic and extrinsic cardiac nerve activity recorded simultaneously. A, Simultaneous ECG, SGNA, LOMNA and VNA recordings showing burst SGNA (arrows on SGNA) occurred alternatively with burst discharges on LOMNA. B, LOMNA preceded (within 1 s) by or co-activated with SGNA discharges suggesting that LOMNA were sympathetic. C, LOMNA activated alternatively with SGNA, leading to a reduction and an increase of HR suggesting that LOMNA contains parasympathetic nerve activity. D, Continuous activation patterns of LOMNA. After SGNA withdrawal, LOMNA started to fire continuously for 81 s during which there was persistent heart rate reduction. Without SGNA and VNA discharges, cyclic pattern of ICNA alone may be associated with either HR acceleration (E) or deceleration (F).

Figure 3

Relationship between intrinsic and extrinsic cardiac nerve activities. A shows that most (94%) of the LOMNA occurred in association with either SGNA or VNA, but occasionally (6%) the LOMNA occurred in the absence of either SGNA or VNA. B, Examples of LOMNA preceded by sympathovagal and SLGPNA co-activation. C shows that SLGPNA always occurs with the ECNA. We found no incidence in which SLGPNA acted alone. D shows an example in which SLGPNA, SGNA and VNA occurred together, while LOMNA was not observed. Arrows indicate the nerve activity.

Figure 4

Induction of PAT by extrinsic and intrinsic cardiac nerve activities. A shows an example in which ICNA occurred before ECNA and a PAT episode. The magnified pseudo ECG shows the different P wave morphologies during sinus rhythm (Aa) and during PAT (Ab). B shows simultaneous ICNA and SGNA leading to the onset of PAT.

Figure 5

ICNA and heart rate acceleration during pre-existing sinus tachycardia. A shows sinus tachycardia following SGNA (dashed arrows). ICNA (downward arrows) induced further shortening of R-R intervals. Panel B shows LOMNA (downward arrow) during pre-existing atrial tachycardia resulted in shortening of atrial cycle length and paradoxical decrement of atrioventricular (AV) conduction. The arrowheads indicate the conducted QRS complexes.

Figure 6

Cardiac nerve activities and conversion from PAT to PAF. Although 28% of PAF was preceded by co-activation of ECNA and ICNA (A), the vast majority of PAF events (72%) were preceded only by ICNA (B). Arrows indicate the nerve activities

Figure 7

ICNA and CFAE at the onset of PAT. A, Local LOM electrograms showed CFAE like signals (dashed arrows) before the onset of PAT episode. The time segments B and C are shown in greater detail in panels B and C, respectively. D, SLGP electrograms show CFAE like signals (dashed arrows) before the onset of a PAT episode. CFAE signals at SLGP occurred simultaneously with SLGPNA (arrows). The time segments E and F are shown in greater detail in panels E and F, respectively.

Figure 8

Histological sections of the LOM recording sites. A shows the hematoxylin and eosin staining. There are nerves and Marshall bundles (MB) in this section. The area marked by a square contains two large nerve bundles. TH staining (B) and ChAT staining (C) showed that these nerve bundles were adrenergic and cholinergic, respectively. Both nerve bundles stained positive with GAP43 staining (D), suggesting active nerve sprouting. Bar, 100 μm.