| The purpose of the present study was to research the relationship between autonomic nervous system and atrial fibrillation(AF) and explore the diagnosis or treatment strategies of AF.In this study, the experiments mainly included the following 3 parts:Part 1. Test the hypothesis that it is feasible to estimate stellate ganglion nerve activity(SGNA) by recording skin nerve activity(SKNA) from the surface of thoracic skin, and explore the relationship between the SKNA and heart rate(HR).Part 2. Study the neural mechanism underlying anti-arrhythmias of low-Level vagal nerve stimulation(LL-VNS) during sustained atrial fibrillation in ambulatory canines.Part 3. Study the efficacy and safety of epicardial circumferential left atrial ablation(CLAA) with pulmonary vein isolation(PVI) in sustained atrial fibrillation.From this study, we concluded that:(1) It is feasible to record sympathetic nerve activities from the surface of skin. SKNAs can be used to estimate SGNA and may be able to predict cardiac arrhythmogenesis.(2) LL-VNS increases inferior vena cava-inferior atrial ganglionated plexus nerve activity(IVC-IAGPNA) and reduces ventricular rate(VR) inambulatory dogs with pacing induced sustained AF. IncreasingIVC-IAGPNA is related to VR control during AF. In addition, LL-VNS couldcause stellate ganglionic cells apoptosis, which is benefit for VR controlduring AF.(3) Epicardial CLAA could ablate the left atrial roof and posterior wall together safely and reliably. Compared with PVI alone, CLAA with PVI may be able to improve the rate of acute termination of persistent AF. It may be useful in selecting the best ablation approaches for patients with persistent AF. Part 1. The Relationship Between Thoracic Skin Nerve Activity and Stellate Ganglion Nerve ActivityObjective: Stellate ganglion nerve activity(SGNA) is important in cardiac arrhythmogenesis. However, direct recording of SGNA requires access to the thoracic cavity. Skin of upper thorax is innervated by sympathetic nerve fibers originating from the stellate ganglia(SG) and is easily accessible. To test the hypothesis that thoracic skin nerve activity(SKNA) can be used to estimate SGNA.Methods: We recorded SGNA and SKNAs using surface electrocardiogram leads in 5 anesthetized and 4 ambulatory dogs. Apamin injected into the right SG abruptly increased both right SGNA and SKNA in 5 anesthetized dogs. We integrated nerve activities and averaged heart rate in each one-min window over 10 min. We implanted a radiotransmitter to record left SGNA in 4 ambulatory dogs. After 2 weeks of recovery, we simultaneously recorded the SKNA and left SGNA continuously for 30 min when the dogs were ambulatory.Results: There was a positive correlation(average r=0.877, 95% confidence interval(CI) 0.732 to 1.000, P <0.05 for each dog) between integrated SKNA(i SKNA) and SGNA(i SGNA) and between i SKNA and heart rate(average r=0.837, 95% CI 0.752 to 0.923, P <0.05). Similar to that found in the anesthetized dogs, there was a positive correlation(average r=0.746, 95% CI 0.527 to 0.964, P <0.05) between i SKNA and i SGNA and between i SKNA and heart rate(average r=0.706, 95% CI 0.484 to 0.927, P <0.05).Conclusions: SKNAs can be used to estimate SGNA in dogs, correlated well with heart rate change. Part 2. The Neural Mechanism of Low-Level Vagal Nerve Stimulation Suppressing Atrial Fibrillation in Ambulatory CaninesObjective: Chronic low-level vagal nerve stimulation(LL-VNS) has been considered to be effective in suppressing atrial fibrillation(AF) induction, but the effect of LL-VNS on AF maintenance was uncertain. Also, the mechanisms by which LL-VNS suppresses AF remain unclear. The aim of this study was to research the Neural Mechanism of Vagal Nerve Stimulation suppressing AF in ambulatory CaninesMethods: A total of 6 dogs were studied. An implantable cardioverter defibrillator was implanted for right atrial pacing. A radiotransmitter was implanted to record inferior vena cava-inferior atrial ganglionated plexus nerve activity(IVC-IAGPNA), right vagal nerve activity(RVNA), left vagal nerve activity(LVNA) and electrocardiogram. A neurostimulator was implanted around left cervical vagal nerve for LL-VNS. After 2 weeks of recovery, high-rate(600bpm) atrial pacing was programed to induce sustained AF. After sustained AF was induced, VNS was programed to 14-s ON and 1.1-min OFF. The output current was increased to 1.5m A in 1~2 weeks. After 1 week of VNS(1.5m A, 1.1min OFF), VNS was programed to 3min OFF. The dog was euthanized after 1 week of VNS(1.5m A, 3min OFF). Both tyrosine hydroxylase(TH) staining and TUNEL detection were performed to observe the effect of LL-VNS on the neural remodeling of bilateral stellate ganglion(SG).Results: All dogs developed sustained AF after 4.00±1.79 weeks(2~6 weeks) of rapid atrial pacing. The average IVC-IAGPNA was significantly increased during both VNS 1.1min OFF(40.98±11.27 m V-s [95% CI, 29.16 to 52.80])(P =0.002) and VNS 3min OFF(39.78±10.14 m V-s [95% CI, 29.14 to 50.42])(P =0.001) versus AF baseline(35.68±10.99 m V-s [95% CI, 24.15 to 47.21]). The VR was significantly reduced during both VNS 1.1-min OFF(123.29±6.29 bpm [95% CI, 116.69 to 129.89])(P =0.001) and VNS 3min OFF(120.01±4.93 bpm [95% CI, 114.84 to 125.18])(P =0.001) compared to AF baseline(142.04±7.93 bpm [95% CI, 133.72 to 150.37]). The reduction of VR during VNS 3min OFF was greater than that of VNS 1.1min OFF(P =0.039). With TH staining, obvious damage region was found in the left SG of all 5 available dogs, but damage region was not visible in the right SG. In the left SG, the size of damage region accounted for 38.6±19.3% [95% CI, 14.7% to 62.5%]. The mean percentage of TH-negative ganglionic cells in damage region(8.4±4.1% [95% CI, 3.3% to 13.6%]) was significantly higher than that in normal region(3.0±1.3% [95% CI, 0% to 6.5%])(P =0.04). However, TUNEL-positive ganglionic cells were found in both left SG and right SG of all 5 available dogs. The mean percentage of TUNEL-positive ganglionic cells was 22.2±17.2% [95% CI, 0.9% to 43.5%] in the left SG and 12.8±8.4% [95% CI, 2.4% to 23.2%] in the right SG, respectively.Conclusions: Chronic LL-VNS increases IVC-IAGPNA and reduces VR in ambulatory dogs with pacing induced sustained AF. Increasing IVC-IAGPNA is related to VR control during AF. In addition, LL-VNS could cause stellate ganglionic cells apoptosis, which is benefit for VR control during AF.Part 3. Effect of epicardial circumferential left atrial ablation with pulmonary vein isolation in atrial fibrillationObjective: The aim of this study was to examine the efficacy and safety of this novel epicardial circumferential left atrial ablation(CLAA) with pulmonary vein isolation(PVI) in sustained atrial fibrillation(AF).Methods: Thirty domestic pigs were divided equally into 3 groups: AF without ablation(AF group), AF with PVI(PVI group), and AF with CLAA and PVI(CLAA+PVI group). AF was induced by rapid atrial pacing. After AF was induced, CLAA and PVI were performed for pigs in CLAA+PVI group, and PVI was performed for pigs in PVI group. AF vulnerability, AF duration, and histology were performed in all groups.Results: All pigs developed sustained AF after 6.27±0.69 weeks of rapid atrial pacing. All pigs successfully underwent isolated PVI or CLAA with PVI on the beating heart in PVI group or CLAA+PVI group. Isolated PVI terminated AF in 3 of 20 pigs(15%), and CLAA with PVI terminated AF in 5 of 8 pigs(62.5%, P=0.022). Compared with AF group(10/10), the incidence of sustained AF by burst pacing was significantly decreased in PVI group(3/10, P=0.003) or CLAA+PVI group(0/10, P<0.001). There was no significant difference between PVI group and CLAA+PVI group(P=0.211). AF duration was significantly decreased in CLAA+PVI group(734.70±177.81 s, 95% CI 607.51 to 861.89) compared with PVI group(1217.90±444.10 s, 95% CI 900.21 to 1535.59, P=0.008). Also, AF duration was significantly decreased in PVI group(P=0.003) or CLAA+PVI group(P<0.001) in comparison with AF duration in AF group(average 1800s).Conclusion: Epicardial CLAA could ablate the left atrial roof and posterior wall together safely and reliably. Compared with PVI alone, CLAA with PVI may be able to improve the rate of acute termination of persistent AF. It may be useful in selecting the best ablation approaches for patients with persistent AF. |
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