TY - JOUR
T1 - Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea
T2 - Implications for Atrial Fibrillation
AU - Tavares, Liliana
AU - Rodríguez-Mañero, Moisés
AU - Kreidieh, Bahij
AU - Ibarra-Cortez, Sergio H.
AU - Chen, Jiexiao
AU - Wang, Sufen
AU - Markovits, Judit
AU - Barrios, Roberto
AU - Valderrábano, Miguel
N1 - Funding Information:
This study was supported by National Institutes of Health/National Heart, Lung, and Blood Institute R01 HL115003 (United States) and the Charles Burnett III and the Lois and Carl Davis Centennial Chair endowments (Houston, TX).
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Background: The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods: Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPS underwent immunohistochemical staining for TRPV1. Results: Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms (P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms (P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions: Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.
AB - Background: The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods: Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPS underwent immunohistochemical staining for TRPV1. Results: Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms (P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms (P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions: Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.
KW - TRPV
KW - atrial fibrillation
KW - autonomic nervous system
KW - obstructive sleep apnea
KW - sensory neurons
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U2 - 10.1161/CIRCEP.118.006942
DO - 10.1161/CIRCEP.118.006942
M3 - Article
C2 - 31164004
AN - SCOPUS:85067443058
SN - 1941-3149
VL - 12
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
IS - 6
M1 - e006942
ER -