Qingyan Zhao

Effect of renal sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged atrial pacing.

We have previously demonstrated that catheter-based renal sympathetic denervation (RSD) could suppress atrial fibrillation (AF) in canines with short-time rapid right atrial pacing (RAP). However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6), the chronic RAP (CRAP) group (n = 7), and the CRAP+RSD group (n = 7). In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05). Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05). RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05). Picric acid–sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05). Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after prolonged RAP in ambulatory canines.

Effects of renal sympathetic denervation on the development of atrial fibrillation substrates in dogs with pacing-induced heart failure.

The present study examined the effect of catheter-based renal sympathetic denervation (RSD) on atrial fibrillation (AF) vulnerability and atrial substrate remodeling in a canine high-rate ventricular pacing model. Animal handling was performed in accordance with theWuhan Directive for Animal Research and the current Guidelines for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH publication no. 85-23, revised 1996). The ethics committee at Wuhan University approved the study protocol. Nineteen adult mongrel dogs were divided into three groups. The pacemakers in the sham-operated group were implanted in a subcutaneous pocket and attached to a pacing lead (Medtronic, Inc., Capture Sense, 4574, USA) in the right ventricular apex. All of the animals recovered for 3 weeks without pacing. The pacemakers were implanted in the heart failure (HF) group, and the dogs underwent ventricular rapid pacing at 240 beats per minute (bpm) for 3 weeks. The dogs in the HF+ RSD group underwent renal artery ablation (RAA) prior to ventricular rapid pacing [1]. After 8 weeks, pacemakers were implanted, and the dogs underwent ventricular rapid pacing for 3 weeks. The femoral artery blood pressure, electrophysiological measurements, echocardiography, left ventricular end-systolic pressure (LVESP), and left ventricular end-diastolic pressure (LVEDP) were measured in all of the animals at baseline and after 3 weeks of pacing. The BNP, Ang II and TNF-α levels were measured in the atrial tissue samples using ELISA and TGF-β was measured using the Western blot. Massons trichrome staining was used to identify increased concentration of interstitial fibrosis.

Renal sympathetic denervation attenuates the ventricular substrate and electrophysiological remodeling in dogs with pacing-induced heart failure

electrophysiological remodeling in dogs with pacing-induced heart failure Zongwen Guo , Qingyan Zhao ⁎, Hongping Deng , Yanhong Tang , Xiaozhan Wang , Zixuan Dai , Jinping Xiao , Peixing Wan , Xule Wang , He Huang , Congxin Huang a,⁎ a Cardiovascular Research Institute of Wuhan University, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan City, 430060, PR China b Department of Thoracic and Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan City, PR China

Differential Densities of Muscarinic Acetylcholine Receptor and IK,ACh in Canine Supraventricular Tissues and the Effect of Amiodarone on Cholinergic Atrial Fibrillation and IK,ACh

Background: Vagal nerve plays an important role in the induction and maintenance of atrial fibrillation (AF). This study investigated the differential densities of M2 receptor and acetylcholine-induced inward rectifier K+ current (IK,ACh) in atrial appendage, atrium, pulmonary vein (PV) and super vena cava (SVC) to discuss the role of atrial appendage and PV in cholinergic AF. Methods and Results: In 10 dogs, action potential duration was determined at 24 sites during bilateral cervical vagal stimulation and amiodarone administration. AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Amiodarone decreased the initiation of AF in vivo. Western blot and patch clamp were used to determine M2 receptor and IK,ACh in RAA, LAA, RA, LA, PV and SVC. The densities of M2 receptor and IK,ACh in LAA, RAA and LA were higher than that in RA, PV and SVC (21.34 ± 0.92 vs. 8.24 ± 0.45 pA/pF, p < 0.05). Furthermore, the densities of the M2 receptor and IK,ACh in LAA and RAA were higher than that in LA (21.34 ± 0.92 vs. 14.17 ± 0.65 pA/pF, p < 0.05). After amiodarone administration, densities of IK,ACh in LA and RA were not different, but densities of IK,ACh were also less in atrium than in atrial appendage. Conclusions: Densities of the M2 receptor and IK,ACh are higher in atrial appendage than other sites. Atrial appendage perhaps plays an important role in initiation of cholinergic AF. However, PV and SVC less often play an important role in vagotonic paroxysmal AF. Reduced dispersion of IK,ACh is the mechanism for amiodarone to therapy AF.

Atrial autonomic innervation remodelling and atrial fibrillation inducibility after epicardial ganglionic plexi ablation

AIMS The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated. METHODS AND RESULTS Thirteen dogs were randomly divided into sham-operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/- 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase-positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively). CONCLUSION Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation.

Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing

AIMS The aim of the present study was to explore the effect of renal sympathetic denervation (RSD) on the progression of paroxysmal atrial fibrillation (AF) in canines with long-term intermittent atrial pacing. METHODS AND RESULTS Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (six dogs), and RSD group (seven dogs). Sham-operated group were implanted with pacemakers without pacing; control group were implanted with pacemakers with long-term intermittent atrial pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Atrial pacing was maintained for 8 h a day and a total of 12 weeks in the control group and RSD group. Echocardiography showed that the left atrial structure and function were significantly improved in the RSD group compared with the control group (P < 0.05). Compared with the control group, the RSD group had fewer incidences of AF and a shorter duration of AF (P < 0.05) after long-term intermittent atrial pacing. In addition to increased atrial effective refractory period (AERP) and AF cycle length, AERP dispersion and P-wave duration and dispersion were significantly decreased in the RSD group compared with the control group (P < 0.05). Atrial morphological evaluation suggested that fibrosis and ultrastructural changes induced by long-term intermittent atrial pacing were markedly suppressed in the RSD dogs compared with controls (P < 0.05). Immunohistochemistry results showed that connexin 43 distribution in RSD mid-myocardial was significantly fewer heterogeneous than that in control mid-myocardial (P < 0.05). CONCLUSION Renal denervation inhibits the progression of paroxysmal AF, which might be related to the suppression of atrial electrophysiology and structural heterogeneity.

Relationship between Autonomic Innervation in Crista Terminalis and Atrial Arrhythmia

Background : The crista terminalis (CT) is known to initiate and maintain atrial arrhythmia, and is affected by autonomic tone, but the underlying mechanisms are poorly understood. This study sought to study the relation between autonomic innervation in CT and atrial arrhythmia.

Effect of anxiety and depression on the recurrence of paroxysmal atrial fibrillation after circumferential pulmonary vein ablation.

Effect of Anxiety and Depression on the Recurrence of Paroxysmal Atrial Fibrillation. Introduction: Whether circumferential pulmonary vein ablation (CPVA) can alleviate anxiety and depression symptoms is unknown and the effect of anxiety and depression on the recurrence of atrial fibrillation (AF) after CPVA is not clear.

Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in Experimental Pulmonary Artery Hypertension.

Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter (AFL), is common in patients with pulmonary arterial hypertension (PAH), who often have increased sympathetic nerve activity. Here, we tested the hypothesis that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The atrial effective refractory period and AF/AFL inducibility at baseline and after anterior right ganglionated plexi ablation were determined during left stellate ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs with or without PAH. Then, sympathetic nerve, &bgr;-adrenergic receptor densities and connexin 43 expression in atrial tissues were assessed. The sum of the window of vulnerability to AF/AFL was increased in the right atrium compared with the left atrium at baseline in the PAH dogs but not in the controls. The atrial effective refractory period dispersion was increased in the control dogs, but not in the PAH dogs, during left stellate ganglion stimulation. The voltage thresholds for inducing AF/AFL during anterior right ganglionated plexi stimulation were lower in the PAH dogs than in the controls. The AF/AFL inducibility was suppressed after ablation of the anterior right ganglionated plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and &bgr;1-adrenergic receptor densities, increased levels of nonphosphorylated connexin 43, and heterogeneous connexin 43 expression in the right atrium when compared with the control dogs. The anterior right ganglionated plexi play important roles in the induction of AF/AFL. AF/AFL induction was associated with right atrium substrate remodeling in dogs with PAH.

Changes in Atrial Effective Refractory Period and I KACh After Vagal Stimulation Plus Rapid Pacing in the Pulmonary Vein

INTRODUCTION AND OBJECTIVES Recent studies have shown that rapid atrial pacing causes atrial electrical remodeling. However, the influence of the vagus nerve on atrial electrical remodeling is not clear. METHODS This study involved 24 dogs divided into three groups. In the control group, the inducibility of atrial fibrillation (AF) during vagal stimulation (VS(1)) was investigated. In the pacing group, the atrial effective refractory period (AERP) was determined before and after pacing in the left superior pulmonary vein (LSPV). In the vagal stimulation (VS) plus pacing group, the LSPV was subjected to rapid electrical pacing after vagal stimulation (VS(2)), and the AERP was measured both before VS(2) and after pacing. The I(KACh) density was measured in LSPV and atrial myocardial cells in the three groups using the patch-clamp technique. RESULTS The duration of induced AF was greater in the pacing group than in the control or VS-plus-pacing group. In the pacing group, the AERP was markedly shortened and the AERP dispersion (dAERP) was significantly increased (P< .05). However, there was no significant change in AERP in the VS-plus-pacing group, though the dAERP increased significantly (P< .05). The I(KACh) density was increased in LSPV and atrial myocardial cells after pacing. However, there was no significant change in I(KACh) density after VS(2) plus pacing. CONCLUSIONS Although shortening of the AERP may play a fundamental role, it is not in itself responsible for cholinergically induced AF. Rapid pacing in the LSPV increased the I(KACh). However, VS before rapid pacing partly protected the atria against electrical remodeling.