Abstract Background Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines. Objectives This study examined the antiarrhythmic and ...anti-inflammatory effects of LLTS in humans. Methods Patients with paroxysmal AF who presented for AF ablation were randomized to either 1 h of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 h of LLTS or sham treatment. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor alpha and C-reactive protein, using a multiplex immunoassay. Results There were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared with baseline in the LLTS group, but not in the control subjects (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in control subjects (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus tumor necrosis factor (TNF)-alpha and C-reactive protein levels decreased significantly only in the LLTS group. Conclusions LLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF.
Objectives We hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS). Background Previously, we showed that VNS can be ...antiarrhythmogenic. Methods Thirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9). Results Group 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms both p < 0.001; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms both p < 0.001). Conclusions LL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results.
Objectives This study was conducted to simulate sleep apnea-induced atrial fibrillation (AF) in an experimental model and to determine whether neural ablation will prevent AF. Background An ...increasing number of clinical reports have associated sleep apnea and AF, and many possible mechanisms responsible for this relationship have been proposed. Methods Thirty dogs anesthetized with Na-pentobarbital were ventilated by a positive pressure respirator. Protocol 1 (n = 14): After a right thoracotomy, atrial and pulmonary vein programmed pacing at 2× and 4× threshold determined the shortest atrial refractory period. Obstructive apnea was induced by turning off the respirator during end expiration for 2 min. During apnea, programmed pacing was performed with S1-S2 = 5 to 10 ms earlier than the atrial refractory period. Neural activity was monitored from the ganglionated plexi (GP) adjacent to the right pulmonary veins. Protocol 2 (n = 16): Electrical stimulation identified the GP at the right pulmonary artery (RPA). Programmed pacing was again instituted, below atrial refractory period, during 2 min of apnea. After radiofrequency ablation of the RPA GP, continuous programmed pacing was again repeated during 2 min of apnea. In 5 dogs, blood gases were determined at baseline and at 2 min of apnea. Results Protocol 1: During apnea, S1-S2 induced AF within 85 ± 38 s (9 of 10). In 1 case, AF occurred spontaneously at 1 min 36 s of apnea. Recorded GP neural activity progressively increased before AF onset. Systolic but not diastolic blood pressure rose significantly before AF (149 ± 26 mm Hg to 193 ± 38 mm Hg, p < 0.05). In 4 dogs, autonomic blockade prevented apnea-induced AF. Protocol 2: AF induced by pacing occurred in 8 of 11 dogs within the 2-min period of apnea, before neural ablation. After ablation, 0 of 6 showed AF during 2 min of apnea (p = 0.009). Conclusions This experimental model of apnea shows a reproducible incidence of AF. After neural ablation of the RPA GP or autonomic blockade, AF inducibility was significantly inhibited.
The mechanism(s) underlying the maintenance of atrial fibrillation (AF) during the first few hours after AF was initiated remains poorly understood.
To investigate the roles of the intrinsic cardiac ...autonomic nervous system in the maintenance of AF at the early stage.
In 10 anesthetized dogs, we attached multielectrode catheters on atria and pulmonary veins. Microelectrodes inserted into the anterior right ganglionated plexi recorded neural activity. At baseline, programmed stimulation determined the effective refractory period (ERP) and window of vulnerability (WOV), a measure of AF inducibility. For the next 6 hours, AF was simulated by rapid atrial pacing (RAP) and the same parameters were measured hourly during sinus rhythm. A circular catheter was positioned in the superior vena cava for high-frequency stimulation (20 Hz) of the adjacent vagal preganglionics. During 4-6 hours of RAP, we delivered low-level vagal stimulation in the superior vena cava (LL-SVCS), 50% below that which induced slowing of the sinus rate.
During the 6-hour RAP, there was a progressive decrease in the ERP and an increase in ERP dispersion, WOV, and neural activity. With LL-SVCS during 4-6-hour RAP, ERP, WOV, and neural activity returned toward baseline levels (all P <.05, compared with the third-hour RAP values).
RAP not only induces atrial electrical remodeling but also promotes autonomic remodeling. These 2 remodeling processes may form a vicious cycle and each may perpetuate the other. These findings may help to explain how AF maintains itself in its very early stage. LL-SVCS both reversed remodeling processes and can potentially break the vicious cycle of "AF begets AF" in the first few hours of AF.
Background.
The intrinsic cardiac autonomic nervous system (ICANS), which forms a neural network, has been shown to be a critical element responsible for the initiation and maintenance of atrial ...fibrillation (AF). We developed a technique to localize and ablate the ganglionated plexi (GP), which serves as the “integration centers” of the ICANS.
Method.
The four major atrial GP are localized by delivering high frequency stimulation (HFS; 20 Hz, 10–150 V, 1–10 ms pulse width) to atrial tissue where GP are presumed to be located. Sites showing a parasympathetic response, which is arbitrarily defined as ≥50% increase in mean R‐R interval during AF, was assigned as a GP site. Radiofrequency current is then applied to that site to eliminate the parasympathetic response. All patients received ablation of the four major atrial GP, followed by pulmonary vein antrum ablation.
Results.
Our preliminary results showed that all the four major atrial GP can be identified in the vast majority of patients. The parasympathetic response can be eliminated by applying radiofrequency current. In the first 83 patients, the percent of patients free of symptomatic AF or atrial tachycardia after a single ablation procedure was 80% at 12 months and 86% at a mean follow‐up of 22 months.
Conclusion.
These results indicate additional benefits of GP ablation to PV antrum ablation and improvement with time, particularly ≥ 12 months after ablation. We postulate that this late benefit may result from destruction of the autonomic neurons in the GP that cannot regenerate.
An open-irrigated radiofrequency (RF) ablation catheter was developed to measure contact force (CF). Three optical fibers measure microdeformation of the catheter tip. The purpose of this study was ...to (1) validate the accuracy of CF sensor (CFS) (bench test); and (2) determine the relationship between CF and tissue temperatures, lesion size, steam pop, and thrombus during RF ablation using a canine thigh muscle preparation.
CFS measurements (total 1409) from 2 catheters in 3 angles (perpendicular, parallel, and 45 degrees ) were compared with a certified balance (range, 0 to 50 g). CFS measurements correlated highly (R(2) > or =0.988; mean error, < or =1.0 g). In 10 anesthetized dogs, a skin cradle over the thigh muscle was superfused with heparinized blood at 37 degrees C. A 7F catheter with 3.5-mm saline-irrigated electrode and CFS (Endosense) was held perpendicular to the muscle at CF of 2, 10, 20, 30, and 40 g. RF was delivered (n=100) for 60 seconds at 30 or 50 W (irrigation 17 or 30 mL/min). Tissue temperature (3 and 7 mm depths), lesion size, thrombus, and steam pop increased significantly with increasing CF at each RF power. Lesion size was greater with applications of lower power (30 W) and greater CF (30 to 40 g) than at high power (50 W) with lower CF (2 to 10 g).
This novel ablation catheter, which accurately measures CF, confirmed CF is a major determinant of RF lesion size. Steam pop and thrombus incidence also increases with CF. CFS in an open-irrigated ablation catheter that may optimize the selection of RF power and application time to maximize lesion formation and reduce the risk of steam pop and thrombus.
A canine right atrial (RA) linear lesion model was used to produce a complex pattern of RA activation to evaluate a novel mapping system for rapid, high resolution (HR) electroanatomical mapping.
The ...mapping system (Rhythmia Medical, Incorporated) uses an 8F deflectable catheter with a minibasket (1.8 cm diameter), containing 8 splines of 8 electrodes (total 64 electrodes, 2.5 mm spacing). The system automatically acquires electrograms and location information based on electrogram stability and respiration phase. In 10 anesthetized dogs, HR-RA map was obtained by maneuvering the minibasket catheter during sinus rhythm and coronary sinus pacing. A right thoracotomy was performed, and either 1 or 2 (to create a gap) epicardial linear lesions were created on the RA free wall (surgical incision or epicardial radiofrequency lesions). RA maps during RA pacing close to the linear lesions were obtained. A total of 73 maps were created, with 44 to 729 (median 237) beats and 833 to 12 412 (median 3589) electrograms (≤2 to ≤5 mm from surface geometry), resolution 1.8 to 5.3 (median 2.7) mm, and 2.6 to 26.3 (median 7.3) minutes mapping time. Without manual annotation, the system accurately created RA geometry and demonstrated RA activation, identifying the location of lines of block and presence or absence of a gap in all 10 dogs. Endocardial radiofrequency catheter ablation of a gap (guided by activation map) produced complete block across the gap in all 3 dogs tested.
The new HR mapping system accurately and quickly identifies geometry and complex patterns of activation in the canine RA, with little or no manual annotation of activation time.
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