Effective Refractory Period Dispersion Research Articles

Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways.

Can the spinal cord stimulation (SCS) regulate the autonomic nerves through the endothelin-1 (ET-1) and nerve growth factor (NGF)/p75NTR pathways and thus inhibit the occurrence of atrial fibrillation (AF)? In our research, 16 beagles were randomly divided into a rapid atrial pacing (RAP) group (n = 8) and a RAP + SCS group (n = 8), and the effective refractory period (ERP), ERP dispersion, AF induction rate, and AF vulnerability window (WOV) at baseline, 6 h of RAP, 6 h of RAP + SCS were measured. The atrial tissue was then taken for immunohistochemical analysis to determine the localization of ET-1, NGF, p75NTR, NF-kB p65, and other genes. Our results showed that SCS attenuated the shortening of ERP in all parts caused by RAP, and after 6 h of SCS, the probability of AF in dogs was reduced compared with that in the RAP group. Moreover, the expression of ET-1, NGF, and p75NTR in the atrial tissues of dogs in the RAP + SCS group was significantly increased, but the expression of NF-kB p65 was reduced. In conclusion, SCS promotes the positive remodeling of cardiac autonomic nerves by weakening NFκB p65-dependent pathways to interfere with the ET-1 and NGF/p75NTR pathways to resist the original negative remodeling and inhibit the occurrence of AF.

Temporal and Spatial Changes of Proarrhythmic Substrate in Premature Ventricular Contraction–Induced Cardiomyopathy

BackgroundThe changes in proarrhythmic substrates and malignant ventricular arrhythmia mechanisms caused by premature ventricular contraction–induced cardiomyopathy (PVCCM) remain unclear. ObjectivesThe goal of this study was to establish the electrophysiological mechanism of how high-load PVC causes malignant arrhythmia. MethodsThirteen swine were exposed to 50% paced PVC from the right ventricular apex for 12 weeks (PVCCM, n = 6) and no pacing for 12 weeks (control, n = 7). Cardiac function was quantified biweekly with echocardiography. Computed tomography scans and electrophysiological examinations were performed monthly to dynamically evaluate the changes in the cardiac structure and the arrhythmogenic substrate. ResultsThe decreases in the cardiac function and ventricular enlargement in the PVCCM group were significant after 12 weeks of PVC stimulation compared with the control group (P < 0.001). Electrophysiological examination found that the ventricular effective refractory period dispersion (0.071 ± 0.008), area of the low-voltage zone (9.41 ± 1.55 cm2), and malignant ventricular arrhythmia inducibility (33.3%) of the PVCCM group increased significantly at week 8 after pacing (P < 0.001 vs the control group); these changes slowed down after 8 weeks. Moreover, the distribution of the low-voltage zone presented obvious spatial heterogeneity, especially in the anterior wall of the right ventricle, accompanied by delayed activation in the sinus rhythm (67 ± 13 milliseconds). Consistently, the proportion of ventricular fibrosis– and expression-related proteins were significantly increased in the PVCCM group (P < 0.001), especially in the right ventricle. Moreover, proteomic analysis confirmed the spatial profile of these fibrotic changes in the PVCCM group. ConclusionsHigh-burden PVC can cause significant temporal and spatial heterogeneity changes in proarrhythmic substrates, which are potentially related to the upregulation of calcium signaling caused by asynchronous activation.

LL-VNS attenuates SK2 expression and incidence of arrhythmias following acute myocardial infarction in rats.

Our previous study has demonstrated that low-level vagus nerve stimulation (LL-VNS) protects the heart against ventricular arrhythmias (VAs) induced by acute myocardial infarction (AMI). However, the potential mechanisms by which it influences ventricular electrophysiology remain unknown. Forty-five rats were divided into three groups: a Control group (sham AMI followed by sham LL-VNS, n = 15), an AMI group (AMI followed by sham LL-VSN for 60 mins, n = 15), and an AMI + LL-VNS group (AMI followed by LL-VSN for 60 mins, n = 15). Heart rate variability (HRV), ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and left stellate ganglion (LSG) activity were measured at baseline and during AMI. Finally, myocardial tissues were collected for tissue analysis. AMI directly induced hyperactivity in the LSG and reduced vagal tone as indexed by HRV. AMI also decreased VFT, and shortened ERP but increased ERP dispersion. AMI resulted in an increase in expression of ventricular small-conductance Ca2+-activated K+ (SK2). However, LL-VNS significantly mitigated or eliminated the effects of AMI. LL-VNS altered the electrophysiological properties of the ventricles through inhibition of cardiac sympathetic nervous activity and reduction in SK2 expression.

The role of alcohol consumption on echocardiographic and electrophysiologic changes in atrial fibrillation.

A wealth of evidence suggests that alcohol consumption is a risk factor for atrial fibrillation (AF); however, the mechanisms underlying this association are unclear. This makes it challenging to develop therapeutic strategies in patients with AF attributed to alcohol consumption. To investigate the echocardiographic and electrophysiologic changes caused by alcohol consumption in patients with AF. The study was registered in Chinese Clinical Trial Registry (Registration number ChiCTR2000041575). Data on 134 consecutive non-valvular AF patients who underwent radiofrequency catheter ablation in our center was collected from April 1, 2019 to June 30, 2020. Patients were divided into no-alcohol (72) and alcohol groups [categorized into light (34), moderate (11) and heavy (17) alcohol consumption]. All patients underwent echocardiographic and electrophysiologic examinations for the assessment of left atrial (LA) strain, inter-atrial conduction, intra-atrial conduction, and atrial effective refractory period (ERP). Overall, the mean age was 61 ± 11 years and 87 (65%) were males. Compared with the no-alcohol group, impaired peak LA longitudinal strain, obvious inter-atrial conduction delay and increasing ERP dispersion were observed in the alcohol group. Intra-atrial conduction delay and ERP dispersion increased with increasing amounts of alcohol consumption. Alcohol consumption was associated with substantial abnormal echocardiographic and electrophysiologic changes in AF patients. These changes may contribute to the occurrence and progression of AF attributed to alcohol consumption, which may help in the development of new strategies for the prevention and management of AF. However further investigation is required.

Location and coupling interval of an ectopic excitation determine the initiation of atrial fibrillation from the pulmonary veins.

IntroductionEctopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs.MethodsPacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior PVs (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP), and conduction properties within the PVs were analyzed.ResultsA single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI‐dependent anisotropic conduction at the AF onset was visualized in a three‐dimensional mapping. Onset of AF was site‐specific with reproducibility in each individual. Mean ERP in LSPV in the AF‐inducible group was shorter than that in the AF‐noninducible group (182 ± 55 vs. 254 ± 51 ms, p < .0001). LSPV ERP dispersion was greater in the AF‐inducible group than in the AF‐noninducible group (45 ± 28 vs. 27 ± 19 ms, p < .01). Circumferential intra‐PV conduction time (IPVCT) exhibited decremental properties in response to shortening of CI and the prolongation of IPVCT in the AF‐inducible site was greater than that in the AF‐noninducible site (p < .05) in each individual.ConclusionsLocation and CI of an ectopic excitation ultimately determine the initiation of AF from the PVs. ERP dispersion and circumferential conduction delay may lead to anisotropic conduction and reentry within the PVs that initiate AF.

The Role of α7nAChR-Mediated Cholinergic Anti-Inflammatory Pathway in Vagal Nerve Regulated Atrial Fibrillation.

The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.

Low-Level Stimulation and Ethanol Ablation of the Vein of Marshall Prevent the Vagal-Mediated AF.

Background: The mechanisms for the vein of Marshall (VOM) mediated atrial fibrillation (AF) are not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in VOM mediated AF.Method: Seven mongrel dogs were administered propranolol and continuously exposed to left superior ganglionated plexi (LSGP) stimulation, LSGP + low-level VOM stimulation, LSGP + atropine administration, LSGP + VOM filling with ethanol separately. The effective refractory period (ERP) and window of vulnerability (WOV) at the left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV) and left atrial appendage (LAA) were measured.Result: LSGP stimulation significantly shortens the ERP and prolonged the ERP dispersion and WOV in LSPV, LIPV, and LAA. Interestingly, low-level VOM stimulation, atropine administration, or VOM filling with ethanol were able to attenuate the effects of LSGP in all sites.Conclusion: VOM as an inter-communication pathway of ganglionated plexis plays an important role in the development of vagal-related AF.

Ganglionated Plexi Ablation Suppresses Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Inhibiting Cardiac Autonomic Hyperactivation.

Background: Previous studies have reported that right pulmonary artery ganglionated plexi (GP) ablation could suppress the onset of atrial fibrillation (AF) associated with obstructive sleep apnea (OSA) within 1 h.Objective: This study aimed to investigate the effect of superior left GP (SLGP) ablation on AF in a chronic OSA canine model.Methods and Results: Fifteen beagles were randomly divided into three groups: control group (CTRL), OSA group (OSA), and OSA + GP ablation group (OSA + GP). All animals were intubated under general anesthesia, and ventilation-apnea events were subsequently repeated 4 h/day and 6 days/week for 12 weeks to establish a chronic OSA model. SLGP were ablated at the end of 8 weeks. SLGP ablation could attenuate the atrial effective refractory period (ERP) reduction and decrease ERP dispersion, the window of vulnerability, and AF inducibility. In addition, chronic OSA leads to left atrial (LA) enlargement, decreased left ventricular (LV) ejection fraction, glycogen deposition, increased necrosis, and myocardial fibrosis. SLGP ablation reduced the LA size and ameliorated LV dysfunction, while myocardial fibrosis could not be reversed. Additionally, SLGP ablation mainly reduced sympathovagal hyperactivity and post-apnea blood pressure and heart rate increases and decreased the expression of neural growth factor (NGF), tyrosine hydroxylase (TH), and choline acetyltransferase (CHAT) in the LA and SLGP. After SLGP ablation, the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, cholesterol metabolism pathway, and ferroptosis pathway were notably downregulated compared with OSA.Conclusions: SLGP ablation suppressed AF in a chronic OSA model by sympathovagal hyperactivity inhibition. However, there were no significant changes in myocardial fibrosis.

Role of Ganglionated Plexus Ablation in Atrial Fibrillation on the Basis of Supporting Evidence.

The role of the autonomic nervous system (ANS) in the onset and maintenance of atrial fibrillation (AF) may be related to autonomic imbalance. The ANS may cause specific cellular electrophysiological phenomena, such as, shortening of the atrial effective refractory periods (ERPs) and ectopy based on firing activity in pulmonary vein myocytes. High frequency stimulation of atrial ganglionated plexi (GPs) may cause an increase in ERP dispersion and induce AF. Autonomic modification strategies by targeting GPs with catheter ablation have emerged as new targets. Various strategies have been used to detect location of GPs.However, it is still not clear which is the best method to localize GPs, how many GPs should be targeted, and what are the long-term consequences of these therapies. In this review, we discuss available evidence on the clinical impact of GP ablation to treat AF.

Metformin regulates adiponectin signalling in epicardial adipose tissue and reduces atrial fibrillation vulnerability

Epicardial adipose tissue (EAT) remodelling is closely related to the pathogenesis of atrial fibrillation (AF). We investigated whether metformin (MET) prevents AF‐dependent EAT remodelling and AF vulnerability in dogs. A canine AF model was developed by 6‐week rapid atrial pacing (RAP), and electrophysiological parameters were measured. Effective refractory periods (ERP) were decreased in the left and right atrial appendages as well as in the left atrium (LA) and right atrium (RA). MET attenuated the RAP‐induced increase in ERP dispersion, cumulative window of vulnerability, AF inducibility and AF duration. RAP increased reactive oxygen species (ROS) production and nuclear factor kappa‐B (NF‐κB) phosphorylation; up‐regulated interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in LA and EAT; decreased peroxisome proliferator‐activated receptor gamma (PPARγ) and adiponectin (APN) expression in EAT and was accompanied by atrial fibrosis and adipose infiltration. MET reversed these alterations. In vitro, lipopolysaccharide (LPS) exposure increased IL‐6, TNF‐α and TGF‐β1 expression and decreased PPARγ/APN expression in 3T3‐L1 adipocytes, which were all reversed after MET administration. Indirect coculture of HL‐1 cells with LPS‐stimulated 3T3‐L1 conditioned medium (CM) significantly increased IL‐6, TNF‐α and TGF‐β1 expression and decreased SERCA2a and p‐PLN expression, while LPS + MET CM and APN treatment alleviated the inflammatory response and sarcoplasmic reticulum Ca2+ handling dysfunction. MET attenuated the RAP‐induced increase in AF vulnerability, remodelling of atria and EAT adipokines production profiles. APN may play a key role in the prevention of AF‐dependent EAT remodelling and AF vulnerability by MET.

C-type natriuretic peptide suppresses ventricular arrhythmias in rats with acute myocardial ischemia

This study aimed to investigate the effects of C-type natriuretic peptide (CNP) on ventricular arrhythmias in rats with acute myocardial ischemia (AMI). Forty male Sprague-Dawley rats were randomly divided into sham group (n = 10), AMI group (n = 15) and AMI + CNP group (n = 15). AMI model was induced by ligating the left anterior descending branch of the coronary artery, and CNP was pumped through the femoral vein starting 30 min before ischemia and continuing until 1 h after AMI. The occurrence of ventricular arrhythmias after ischemia and heart rate variability (HRV) were recorded and analyzed. The plasma norepinephrine level was detected at 15 min after AMI. Ventricular electrophysiological parameters including ventricular effective refractory period (ERP), ERP dispersion, ventricular action potential duration (APD) alternans and ventricular fibrillation threshold (VFT) were measured one hour after AMI. Then, the expressions of cyclic guanosine monophosphate in myocardial tissue and left stellate ganglion were examined. Compared to sham group, AMI significantly shortened the ERP, augmented ERP dispersion, elevated APD alternans cycle length, reduced VFT, and increased the incidence of ventricular arrhythmias. Moreover, AMI increased the sympathetic component of HRV, raised plasma norepinephrine levels, and decreased the cyclic guanosine monophosphate levels in myocardium and left stellate ganglion. All those changes were attenuated by CNP treatment. These findings suggest that CNP protected against ventricular arrhythmias in rats with AMI, potentially by inhibiting ischemia-induced cardiac sympathetic hyperactivity and cardiac electrophysiology instability.

Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats

Even though ethanol consumption has been associated with risk of atrial fibrillation (AF), little is known about how ethanol affects atrial electrophysiology. The purpose of this study was to study the electrophysiological effect of ethanol on rat AF. Atrial optical mapping was performed on male Long Evans rat hearts with escalating concentrations of ethanol (0, 1, 2, and 3 mM). In addition, patch-clamp recordings on isolated atrial myocytes were performed. In chronic ethanol study, rats were divided into control and chronic ethanol groups (20% ethanol in drinking water for 6 months). Atrial optical mapping, histology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were performed in chronic rats. Acute ethanol perfusion increased AF vulnerability (0% at 0 mM, 0% at 1 mM, 57.1% at 2 mM, and 100% at 3 mM) in a dose-related response. Ethanol infusion decreased conduction velocities (CVs) in both atria and shortened effective refractory periods (ERP) only in the right atria with increased in dispersion of refractoriness. Action potential duration at 50% and 90% repolarization from right atrial myocytes were shortened, with corresponding increase of sustained potassium current. Chronic ethanol consumption increased AF inducibility (10% control vs 95.2% chronic ethanol). CVs in both atria were significantly decreased. ERP of the right atrium was shortened, and dispersion of ERP was increased. Expression (mRNA) of KCNQ1 and connexin40 were increased, but KCNA5 was decreased in the right atrium of rats exposed to chronic ethanol. Acute and chronic exposure to ethanol increases AF vulnerability by slowing CV, shortening right atrial ERP, and increasing dispersion of ERP.

Electrophysiological Cardiac Parameters and Results of Antiarrhythmic Treatment in Patients with Paroxysmal Atrial Fibrillation (Lone and Associated with Arterial Hypertension)

to assess cardiac electrophysiological parameters in patients with paroxysmal atrial fibrillation (AF), lone or with concomitant arterial hypertension (AH), and their prognostic significance relative to treatment effectiveness. We included in this study 184 patients with paroxysmal AF (84 with concomitant AH and 100 with presumed lone AF). Cardiac electrophysiological study was performed in accordance with standardized protocol that included assessment of sinus node recovery time, sinoatrial, intraatrial and interatrial conduction time, and effective refractory periods (ERP) of right and left atria and atrioventricular node. Patients with inducible supraventricular reentrant arrhythmias that could potentially trigger AF underwent catheter radiofrequency ablation of those arrhythmias. Other patients received either antiarrhythmic drug therapy (AAD; n=79) or catheter cryo-ablation (CBA; n=81). Treatment was considered ineffective in case of any symptomatic or asymptomatic AF episode documented by ECG or Holter ECG within 12 months of follow-up. Patients with lone AF compared with those with AH had shorter ERP of the right atrium (219±21 ms vs. 253±44 ms, respectively, p&lt;0.05) and more prominent dispersion of ERP of right and left atria (median 40 ms, interquartile range 10-50 ms vs. median 20 ms, interquartile range 10-22.5 ms, respectively, p&lt;0.05). There was no statistically significant difference in other electrophysiology parameters between the groups. Sustained supraventricular reentrant arrhythmias were induced in 9% (9 of 100) patients with presumed lone AF and in 1.2% (1 of 84) patients with AH (p&lt;0.05). All these arrhythmias were successfully ablated, and patients had no AF recurrence during 12-month follow-up. Among other patient treatment (CBA n=81, AAD n=79) was effective in 64% of those with lone AFib and in 34% - with AH (p&lt;0.05). In multivariate multiple regression analysis, none of electrophysiological parameters could be assumed as a factor associated with the efficacy of CBA or AAD. Patients with lone AF had more prominent atrial electrophysiological inhomogeneity compared with patients with concomitant AH. Cardiac electrophysiological parameters had no influence on effectiveness of antiarrhythmic treatment.

Effect of remote ischemic preconditioning on electrophysiological parameters in nonvalvular paroxysmal atrial fibrillation: The RIPPAF Randomized Clinical Trial

Atrial fibrillation (AF) remains the most relevant arrhythmia with a prevalence of 2%. The treatment options are either highly invasive and cost-intensive or limited by potential side effects or insufficient efficacy. However, no direct means of prevention that could reduce the burden of AF have been tested. The purpose of this study was to determine whether remote ischemic preconditioning (RIPC) has an impact on inducibility and sustainability of AF. A total of 146 patients with paroxysmal AF undergoing electrophysiology study were randomized to receive either RIPC, performed by short episodes of forearm ischemia, or sham intervention (clinicaltrials.gov identifier: NCT02779660). Effective refractory periods, conduction times, velocities, and conduction delays measured were analyzed by pacing from the coronary sinus (CS). End points of the study were the inducibility and sustainability of AF after prespecified rapid pacing sequences. RIPC significantly reduces the inducibility (odds ratio 0.35; 95% confidence interval 0.17-0.71; P = .003) and sustainability (odds ratio 0.36; 95% confidence interval 0.16-0.81; P=.01) of AF. Furthermore, it decreased dispersion of atrial refractory periods (16.0 ± 14.0 ms vs 22.7 ± 19.0 ms; P = .021) as well as atrial conduction delays (49.2 ± 19.6 ms vs 56.2 ± 22.5 ms; P =.049 for proximal CS and 42.4 ± 16.6 ms vs 49.8 ± 22.2 ms; P = .029 for distal CS). In the whole cohort, longer atrial conduction delay (57.6 ± 22.2 ms vs 50.0 ± 20.5 ms; P = .044) and slower conduction velocity (1.74 ± 0.3 mm/ms vs 1.93 ± 0.5 mm/ms; P =.006) were associated with inducibility of AF whereas a wider dispersion of effective refractory periods (25.9 ± 18.3 ms vs 15.7 ± 11.6 ms; P = .028) maintained AF episodes. RIPC reduces the inducibility and sustainability of AF, which is possibly mediated by changes in electrophysiological properties of the atria. It may be used as a simple noninvasive procedure to reduce AF burden.

Epicardial ganglionated plexi ablation increases the inducibility of ventricular tachyarrhythmias in a canine postmyocardial infarction model.

Previous studies have shown that epicardial ganglionated plexi ablation (EGPA) could increase the risk of ventricular arrhythmias induced by acute myocardial ischemia. However, the long-term effect of EGPA in a canine postmyocardial infarction (MI) model is not well established. Twenty mongrel dogs were randomly divided into two groups: an MI group (n = 10) and an EGPA group (EGPA plus MI, n = 10). EGPA was achieved by ablation of four major ganglion plexi and the ligament of Marshall. The electrocardiograph (ECG) parameters, ventricular effective refractory period (ERP), inducibility of tachyarrhythmias, and ventricular fibrillation threshold (VFT) were measured at baseline and after 8 weeks. Tyrosine hydroxylase (TH) and nerve growth factor (NGF) expression levels in the peri-infarcted zone were also determined by immunohistochemistry in both groups at the end of the study. No significant differences were found in electrophysiological parameters at the baseline between the two groups. At the end of the 8-week follow-up, however, the EGPA group was associated with a longer QT interval, corrected QT (QTc) interval and ventricular ERP, larger dispersion of QT, QTc, and ERP, and higher inducibility of tachyarrhythmia and VFT when compared to the MI group. In addition, the density of TH and NGF in the peri-infarcted zone was also significantly increased in the EGPA group in comparison to the MI group. After the 8-week follow-up, EGPA increased the ventricular arrhythmia inducibility in the canine post-MI model, likely by increasing ventricular electrophysiological instability and promoting ventricular sympathetic remodeling.

Cardiac Sympathetic Afferent Denervation Protects Against Ventricular Arrhythmias by Modulating Cardiac Sympathetic Nerve Activity During Acute Myocardial Infarction.

BackgroundAugmented cardiac sympathetic afferent reflex (CSAR) plays a role in enhanced sympathetic activity. Given that a strategy for abolishing augmented CSAR-induced sympathetic activation may be beneficial for protecting against ventricular arrhythmias (VAs) triggered by acute myocardial infarction (AMI), we investigated whether cardiac sympathetic afferent denervation (CSAD) could protect against VAs by modulating cardiac sympathetic nerve activity in an AMI dog model.Material/MethodsTwenty-two anesthetized dogs were assigned to the CSAD group (n=9) and the sham group (n=13) randomly. CSAD was produced by epicardial application of resiniferatoxin. Heart rate variability (HRV), ventricular action potential duration (APD), APD dispersion, beat-to-beat variability of repolarization (BVR), effective refractory period (ERP) of ventricles, ERP dispersion, plasma norepinephrine (NE) concentration, and left stellate ganglion (LSG) neural activity were determined at baseline and after CSAD. We designed an AMI model by occluding the left anterior coronary artery, and performed analysis of VAs for 60 minutes using electrocardiography. Then, levels of c-fos and nerve growth factor (NGF) were determined.ResultsRelative to baseline values, CSAD prolonged ERP and APD of ventricles, increased HRV, decreased APD dispersion, BVR, ERP dispersion and serum NE concentration, and attenuated LSG activity in the CSAD group. AMI triggered a remarkable increase in LSG activity and function but decreased the HRV of the sham group animals relative to the CSAD group. Moreover, the CSAD group had higher levels of VAs relative to the sham group. This was accompanied by a corresponding decrease in proteins quantities of NGF and c-fos in the CSAD group in the LSG after AMI compared to the sham group.ConclusionsCSAD can suppress LSG neural activity, hence enhance the electrophysiological stability and protect the heart from AMI-triggered VAs.

Electrophysiological Measurement of Rat Atrial Epicardium Using a Novel Stereotaxic Apparatus.

Flexible, in vivo maneuverable electrophysiology mapping techniques are not available in rat models. A novel cardiac stereotactic electrophysiology epicardial mapping system (CREAMS) allows for various measurements, including: (1) recording unipolar electrograms at multiple sites; (2) positioning of mapped sites and precision testing (Distance between the two "centers" = 297 ± 54 μm, n = 15); (3) evaluation of electrophysiology in an in vivo Sprague-Dawley rat model with high-frequency stimulation (HFS)-induced Atrial fibrillation (AF) at high right atrium (HRA) sites. We found that of the right atrium dispersion of effective refractory period (P < 0.05) and the window of vulnerability (P < 0.01) were significantly increased (P < 0.05) after HRA HFS. CREAMS has the potential for convenient electrophysiology assessment in a rat AF model through stereo-positioning, and flexible operating manipulation.

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability.

Transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) is a potentially noninvasive, inexpensive, and safe approach for vagus nerve stimulation that suppresses the induction and duration of atrial fibrillation and reduces sympathetic nerve outflow in healthy humans. Researchers have not determined whether AB-VNS affects ventricular arrhythmias. To evaluate the antiarrhythmic effects of noninvasive AB-VNS on ventricular arrhythmias induced by myocardial infarction (MI). Twelve beagle dogs were randomly divided into the following two groups: a AB-VNS group (coronary artery occlusion and noninvasive AB-VNS) and a control group (coronary artery occlusion but without AB-VNS). We examined spontaneous ventricular arrhythmias, ventricular electrophysiological properties, and cardiac function in conscious dogs. Morphology, fibrosis, and ultrastructures were also assessed. AB-VNS significantly reduced the occurrence of spontaneous ventricular arrhythmias, including isolated premature ventricular complexes, ventricular couplets, ventricular bigeminy, ventricular trigeminy, and ventricular tachycardia. AB-VNS effectively increased ventricular electrical stability, including significantly prolonged ventricular effective refractory periods, decreased the dispersion of effective refractory period, enhanced the ventricular fibrillation threshold, and decreased the maximum slope of the monophasic action potential duration restitution curve. AB-VNS treatments alleviate ventricular interstitial fibrosis after MI. However, cardiac function was not improved, and MI-induced ultrastructural changes in the myocardium were not reversed by 4weeks of AB-VNS. In addition, AB-VNS for 4weeks resulted in mild mitochondrial swelling within the neuronal axons of the auricular vagus fiber. Noninvasive AB-VNS reduces the occurrence of spontaneous ventricular arrhythmias in conscious dogs with MI. AB-VNS increases ventricular electrical stability and alleviates ventricular interstitial fibrosis induced by MI.

Selective ablation of the ligament of Marshall attenuates atrial electrical remodeling in a short-term rapid atrial pacing canine model.

Cardiac sympathetic activation facilitates atrial electrical remodeling during atrial fibrillation (AF). Selective ablation of the distal part of the ligament of Marshall (LOMLSPV ) could decrease cardiac sympathetic innervation. This study aimed to investigate the effects of LOMLSPV ablation on atrial electrical remodeling in a short-term rapid atrial pacing (RAP) model. In 16 anesthetized dogs, 6hours of RAP (20Hz, 2 × threshold) was delivered before LOMLSPV ablation (group 1, N=8) or after (group 2, N=8). Heart rate variability (HRV), serum norepinephrine (NE), atrial electrophysiological indices were analyzed. Six times of burst pacing (20Hz, 2 × threshold, lasting for 5 seconds, were performed to induce AF, the number of episodes and the duration of AF were compared. LOMLSPV ablation decreased sympathetic indices of HRV and serum NE. Atrial effective refractory period (ERP) was shortened during RAP in both groups with higher reduction degrees in group 1. In group 1, the shortening of atrial ERP, elevating of ERP dispersion and sum of window of vulnerability (ΣWOV), facilitating of AF induced by RAP were subsequently reversed by LOMLSPV ablation. In group 2, LOMLSPV ablation prolonged atrial ERP, decreased ΣWOV, eliminated AF induction. The subsequent RAP failed to alter these indices. Histological studies showed abundant sympathetic nerve fibers in LOMLSPV . LOMLSPV ablation could inhibit atrial electrical remodeling during short-term RAP by reducing the cardiac sympathetic activity. LOMLSPV may be a potential target in AF ablation, especially in patients with highly cardiac sympathetic activation or atrial electrical remodeling.

Time-dependent cervical vagus nerve stimulation and frequency-dependent right atrial pacing mediates induction of atrial fibrillation.

Objective:This study aimed to investigate the effects of right cervical vagus trunk simulation (RVTS) and/or right atrial pacing (RAP) on the induction of atrial fibrillation (AF).Methods:Twenty-four healthy adult dogs were randomly divided into four groups: RAP groups comprising RAP500 (RAP with 500 beats/min) and RAP1000 (RAP with 1000 beats/min) and RVTS groups comprising RVTS and RAP500+RVTS. All dogs underwent 12-h intermittent RAP and/or RVTS once every 2 h. The AF induction rate, AF duration, atrial effective refractory period (ERP), and dispersion of ERP (dERP) were compared after every 2 h of RAP or/and RVTS.Results:All groups had successful AF induction. The RAP1000 group had the highest AF induction rate and the longest AF duration. The RAP1000 group also had a shortened ERP in comparison to the other groups as well as the maximum dERP. Compared to the RAP500 group, RAP500+RVTS had an increased capacity to induce AF as measured by the AF induction rates, AF duration, ERP, and dERP.Conclusion:Increased tension in the vagus nerve and the intrinsic cardiac autonomic nervous system plays an important role in AF induction through different potential mechanisms. Interventions involving the vagus nerve and/or intrinsic cardiac autonomic nervous system can be a future potential therapy for AF.