Abstract
The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M2) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M 2 receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 ± 1, 3.2 ± 2.5, and 0.17 ± 0.3/cm2 in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M 2 distribution was also most pronounced in the PLA (17.8 ± 8.3, 14.3 ± 7.3, and 14.5 ± 8 M2-stained cells/cm 2 in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% (P < 0.001). We conclude that 1) P fibers and M2 receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 294 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2008 |
| Externally published | Yes |
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Keywords
- Autonomic
- Immunohistochemistry
- Nervous system
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Neural substrate for atrial fibrillation : Implications for targeted parasympathetic blockade in the posterior left atrium. / Arora, Rishi; Ulphani, Joseph S.; Villuendas, Roger; Ng, Jason; Harvey, Laura; Thordson, Sarah; Inderyas, Firdous; Lu, Yi; Gordon, David; Denes, Pablo; Greene, Rodney; Crawford, Susan; Decker, Robert; Morris, Alexander; Goldberger, Jeffrey; Kadish, Alan H.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 1, 01.01.2008.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neural substrate for atrial fibrillation
T2 - Implications for targeted parasympathetic blockade in the posterior left atrium
AU - Arora, Rishi
AU - Ulphani, Joseph S.
AU - Villuendas, Roger
AU - Ng, Jason
AU - Harvey, Laura
AU - Thordson, Sarah
AU - Inderyas, Firdous
AU - Lu, Yi
AU - Gordon, David
AU - Denes, Pablo
AU - Greene, Rodney
AU - Crawford, Susan
AU - Decker, Robert
AU - Morris, Alexander
AU - Goldberger, Jeffrey
AU - Kadish, Alan H.
PY - 2008/1/1
Y1 - 2008/1/1
N2 - The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M2) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M 2 receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 ± 1, 3.2 ± 2.5, and 0.17 ± 0.3/cm2 in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M 2 distribution was also most pronounced in the PLA (17.8 ± 8.3, 14.3 ± 7.3, and 14.5 ± 8 M2-stained cells/cm 2 in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% (P < 0.001). We conclude that 1) P fibers and M2 receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.
AB - The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M2) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M 2 receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 ± 1, 3.2 ± 2.5, and 0.17 ± 0.3/cm2 in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M 2 distribution was also most pronounced in the PLA (17.8 ± 8.3, 14.3 ± 7.3, and 14.5 ± 8 M2-stained cells/cm 2 in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% (P < 0.001). We conclude that 1) P fibers and M2 receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.
KW - Autonomic
KW - Immunohistochemistry
KW - Nervous system
UR - http://www.scopus.com/inward/record.url?scp=38149122798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38149122798&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00732.2007
DO - 10.1152/ajpheart.00732.2007
M3 - Article
C2 - 17982017
AN - SCOPUS:38149122798
VL - 294
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 1
ER -