Zixuan Dai

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

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.

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.

Median nerve stimulation prevents atrial electrical remodelling and inflammation in a canine model with rapid atrial pacing.

Aims Studies have shown that stellate ganglion nerve activity has association with atrial electrical remodelling and atrial fibrillation (AF) inducibility, while median nerve stimulation (MNS) decreases cardiac sympathetic drive. In this study, we tested the hypothesis that MNS suppresses atrial electrical remodelling and AF vulnerability. Methods and results The atrial effective refractory period (AERP) and AF inducibility at baseline and after 3 h of rapid atrial pacing were determined in dogs undergoing MNS (n = 7), MNS+ application of methyllycaconitine (n = 7) or sham procedure (n = 6). Then, the levels of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and acetylcholine (Ach) in the plasma and atrial tissues were measured. The control dogs (n = 4) were assigned to measure atrial inflammation cytokines. Short-term rapid atrial pacing induced shortening of the AERP, an increase in AERP dispersion, and an increase AF vulnerability in the sham dogs, which were all suppressed by MNS. Levels of TNF-a and IL-6 were higher, and Ach levels were lower in the left and the right atrium in the sham dogs than in the MNS dogs. Methyllycaconitine blunted the effects of MNS on the AERP, AERP dispersion, the AF vulnerability, and TNF-a and IL-6 levels in the atrium, but had no impact on the levels of Ach. Conclusions The effects of MNS on atrial electrical remodelling and AF inducibility might be associated with the cholinergic anti-inflammatory pathway.

Effects of extrinsic cardiac nerve stimulation on atrial fibrillation inducibility: The regulatory role of the spinal cord: DAI et al.

To investigate the effect of the mutual regulation of the extrinsic cardiac nerves on atrial electrophysiology and atrial fibrillation (AF) vulnerability.

Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity.

Background: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. Methods: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. Results: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms2, P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and &agr;7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. Conclusions: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.

ASSA13-03-7 Renal Sympathetic Denervation Changes the Distribution of Atrial Substrate and Inhibites the Inducibility of Atrial Fibrillation

Objective Whether renal sympathetic denervation has effect on changes of atrial substrate and inducilibity of atrial fibrillation is unknown. The purpose of this study was to determine the effect of renal denervation on the inducibility atrial fibrillation. Methods Thirteen dogs were randomly divided into control group (7 dogs) and renal artery ablation group (6 dogs). In control group, at first, atrial fibrillation was induced by anterior right ganglionated plexi stimulation. Then, rapid atrial pacing was performed for 7 hours. Atrial effective refractory period and atrial fibrillation were measured each hour. In renal artery ablation group, after renal artery ablation, dogs were raised for 6 weeks. After that, the procedure of pacing and electrophysiological measurement was same as in the control group. Results The voltage in the sinus rate slowing response and the threshold of inducilibity atrial fibrillation increased during ganglionated plexi stimulation after renal artery ablation (3.5 ± 1.6V vs 1.6 ± 0.3V; 5.1V ± 1.0V vs 2.1V ± 0.7V, P = 0.03). Induced number of times and duration of atrial fibrillation was higher in control group than that in renal artery ablation group after cessation of pacing. Levels of ANP in right atrium and densities of Cx43 were lower in renal artery ablation group than that in control group (ANP: 220.5 ± 37.6 pg/mg vs 164.4 ± 22.0 pg/mg, P = 0.02; Cx43: 0.52, 0.63, 0.87 vs 1, 1.02, 1.91, P < 0.01). Conclusions Renal sympathetic denervation results in changes of atrial substrate and markedly decrease the inducilibity of atrial fibrillation by inhibiting activity of renin-angiotensin-aldosterone system.

ASSA13-03-6 Effects of Renal Sympathetic Denervation on the Development of Atrial Fibrillation Substrates in Dogs with Pacing-Induced Heart Failure

Objective We examined the role of renal denervation on the inducibility of AF in dogs with pacing-induced HF. Background Atrial fibrillation (AF) and heart failure (HF) are common interrelated conditions that are associated with renin-angiotensin-aldosterone system activity. Methods and Results Nineteen dogs were randomised into sham-operated (7 dogs), HF (6 dogs) and HF+renal artery ablation (RAA, 6 dogs) groups. Sham-operated dogs were implanted with transvenous cardiac pacemakers without pacing. Dogs in the HF group were implanted with pacemakers and underwent right ventricular pacing for 3 weeks at 240 bpm to induce HF. The dogs in the HF+RAA group received double renal artery ablation. The dogs recovered for 8 weeks and underwent the same HF-inducing procedure. Compared to the baseline, the atrial dimensions increased and the right atrial ERP (131 ± 14 ms to 112 ± 12 ms, p = 0.02) decreased significantly after 3 weeks in the HF dogs but not the HF+RAA dogs. A greater number of AFs were induced in the HF dogs than the HF+RAA dogs (2.2 ± 0.6 vs. 0.3 ± 0.3, p = 0.03). The atrium from HF hearts revealed a large amount of fibrosis, whereas control and HF+RAA dogs showed minimal fibrous tissue. The levels of BNP, Ang II, TNF-α and expression of TGF-β and Cx43 in atrial tissue were increased in the HF dogs compared to the sham-operated and HF+RAA dogs. Conclusion RAA suppressed the atrial substrate remodelling and the AF vulnerability that was induced by long-term rapid ventricular pacing.