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Browsing by Author "Jiang, Zhaolei"
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Item Antiarrhythmic effects of stimulating the left dorsal branch of the thoracic nerve in a canine model of paroxysmal atrial tachyarrhythmias(Elsevier, 2018) Zhao, Ye; Yuan, Yuan; Tsai, Wei-Chung; Jiang, Zhaolei; Tian, Zhi-peng; Shen, Changyu; Lin, Shien-Fong; Fishbein, Michael C.; Everett, Thomas H., IV.; Chen, Zhenhui; Chen, Peng-Sheng; Medicine, School of MedicineBackground Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial tachyarrhythmia (PAT) episodes in dogs with intermittent high-rate left atrial (LA) pacing. The left dorsal branch of the thoracic nerve (LDTN) contains sympathetic nerves originating from the stellate ganglia. Objective The purpose of this study was to test the hypothesis that high-frequency electrical stimulation of the LDTN can cause stellate ganglia damage and suppress PAT. Methods We performed chronic LDTN stimulation in 6 dogs with and 2 dogs without intermittent rapid LA pacing while monitoring SGNA. Results LDTN stimulation reduced average SGNA from 4.36 μV (95% confidence interval [CI] 4.10–4.62 μV) at baseline to 3.22 μV (95% CI 3.04–3.40 μV) after 2 weeks (P = .028) and completely suppressed all PAT episodes in all dogs studied. Tyrosine hydroxylase staining showed large damaged regions in both stellate ganglia, with increased percentages of tyrosine hydroxylase–negative cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that 23.36% (95% CI 18.74%–27.98%) of ganglion cells in the left stellate ganglia and 11.15% (95% CI 9.34%–12.96%) ganglion cells in the right stellate ganglia were positive, indicating extensive cell death. A reduction of both SGNA and heart rate was also observed in dogs with LDTN stimulation but without high-rate LA pacing. Histological studies in the latter 2 dogs confirmed the presence of extensive stellate ganglia damage, along with a high percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells. Conclusion LDTN stimulation damages both left stellate ganglia and right stellate ganglia, reduces left SGNA, and is antiarrhythmic in this canine model of PAT.Item Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs(Elsevier, 2017-02) Tsai, Wei-Chung; Chan, Yi-Hsin; Chinda, Kroekkiat; Chen, Zhenhui; Patel, Jheel; Shen, Changyu; Zhao, Ye; Jiang, Zhaolei; Yuan, Yuan; Ye, Michael; Chen, Lan S.; Riley, Amanda A.; Persohn, Scott A.; Territo, Paul R.; Everett, Thomas H., IV; Lin, Shien-Fong; Vinters, Harry V.; Fishbein, Michael C.; Chen, Peng-Sheng; Medicine, School of MedicineBACKGROUND: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. OBJECTIVE: We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. METHODS: We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. CONCLUSION: Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.Item Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation(Elsevier, 2018-08) Jiang, Zhaolei; Zhao, Ye; Tsai, Wei-Chung; Yuan, Yuan; Chinda, Kroekkiat; Tan, Jian; Onkka, Patrick; Shen, Changyu; Chen, Lan S.; Fishbein, Michael C.; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas H.; Medicine, School of MedicineOBJECTIVES: This study was designed to test the hypothesis that low-level vagal nerve stimulation (VNS) reduces the ventricular rate (VR) during atrial fibrillation (AF) through the activation of the inferior vena cava (IVC)-inferior atrial ganglionated plexus nerve activity (IAGPNA). BACKGROUND: Increased IVC-IAGPNA can suppress atrioventricular node conduction and slow VR in canine models of AF. METHODS: Persistent AF was induced in 6 dogs and the IVC-IAGPNA, right vagal nerve activity, left vagal nerve activity, and an electrocardiogram were recorded. After persistent AF was documented, VNS was programed to 14 s "on" and 1.1 min "off." After 1 week, the VNS was reprogramed to 3 min off and stimulation continued for another week. Neural remodeling of the stellate ganglion (SG) was assessed with tyrosine hydroxylase staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining. RESULTS: Average IVC-IAGPNA was increased during both VNS 1.1 min off (8.20 ± 2.25 μV [95% confidence interval (CI): 6.33 to 9.53 μV]; p = 0.002) and 3 min off (7.96 ± 2.03 μV [95% CI: 6.30 to 9.27 μV]; p = 0.001) versus baseline (7.14 ± 2.20 μV [95% CI: 5.35 to 8.52 μV]). VR was reduced during both VNS 1.1 min off (123.29 ± 6.29 beats/min [95% CI: 116.69 to 129.89 beats/min]; p = 0.001) and 3 min off (120.01 ± 4.93 beats/min [95% CI: 114.84 to 125.18 beats/min]; p = 0.001) compared to baseline (142.04 ± 7.93 bpm [95% CI: 133.72 to 150.37]). Abnormal regions were observed in the left SG, but not in the right SG. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive neurons were found in 22.2 ± 17.2% [95% CI: 0.9% to 43.5%] of left SG cells and 12.8 ± 8.4% [95% CI: 2.4% to 23.2%] of right SG cells. CONCLUSIONS: Chronic low-level VNS increases IVC-IAGPNA and damages bilateral stellate ganglia. Both mechanisms could contribute to the underlying mechanism of VR control during AF.Item Ganglionated plexi and ligament of Marshall ablation reduces atrial vulnerability and causes stellate ganglion remodeling in ambulatory dogs(Elsevier, 2016-10) Zhao, Ye; Jiang, Zhaolei; Tsai, Wei-Chung; Yuan, Yuan; Chinda, Kroekkiat; Choi, Eue-Keun; Fishbein, Michael C.; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas H.; Medicine, School of MedicineBackground Simultaneous activation of the stellate ganglion (SGNA), the ligament of Marshall (LOM) and the ganglionated plexi (GP) often precedes the onset of paroxysmal atrial tachyarrhythmias (PAT). Objective To test the hypothesis that ablation of the LOM and the superior left GP (SLGP) reduces atrial vulnerability and results in remodeling of the stellate ganglion. Methods Nerve activity was correlated to PAT and ventricular rate (VR) at baseline, after ablation of the LOM and SLGP, and after AF. Neuronal cell death was assessed with Tyrosine hydroxylase (TH) and terminal deoxynucleotidyl transferase dUTP nick end label (TUNEL) staining. Results There were 4±2 PAT episodes per day in controls. None were observed in the ablation group; even though SGNA and VR increased from 2.2 μV (95% confidence interval (CI); 1.2 – 3.3 μV) and 80 bpm (CI 68 – 92 bpm) at baseline to 3.0 μV (CI 2.6 – 3.4 μV, p=0.046) and 90 bpm (CI 75 – 108 bpm, p=0.026) after ablation, and to 3.1 μV (CI 1.7 – 4.5 μV, p=0.116) and 95 bpm (CI 79 – 110 bpm, p=0.075) after AF. There was an increase in TH-negative cells in the ablation group and a 19.7% (CI, 8.6 – 30.8%) TUNEL-positive staining in both the left and right SG. None were observed in the control group. Conclusion LOM and SLGP ablation caused LSG remodeling and cell death. There was reduced correlation of the VR response and PAT to SGNA. These findings support the importance of SLGP and LOM in atrial arrhythmogenesis.Item Long-term intermittent high-amplitude subcutaneous nerve stimulation reduces sympathetic tone in ambulatory dogs(Elsevier, 2018-03) Yuan, Yuan; Jiang, Zhaolei; Zhao, Ye; Tsai, Wei-Chung; Patel, Jheel; Chen, Lan S.; Shen, Changyu; Lin, Shien-Fong; Chen, Huei-Sheng Vincent; Everett, Thomas H., IV; Fishbein, Michael C.; Chen, Zhenhui; Chen, Peng-Sheng; Medicine, School of MedicineBACKGROUND: Reducing sympathetic efferent outflow from the stellate ganglia (SG) may be antiarrhythmic. OBJECTIVE: The purpose of this study was to test the hypothesis that chronic thoracic subcutaneous nerve stimulation (ScNS) could reduce SG nerve activity (SGNA) and control paroxysmal atrial tachycardia (PAT). METHODS: Thoracic ScNS was performed in 8 dogs while SGNA, vagal nerve activity (VNA), and subcutaneous nerve activity (ScNA) were monitored. An additional 3 dogs were used for sham stimulation as controls. RESULTS: Xinshu ScNS and left lateral thoracic nerve ScNS reduced heart rate (HR). Xinshu ScNS at 3.5 mA for 2 weeks reduced mean average SGNA from 5.32 μV (95% confidence interval [CI] 3.89-6.75) at baseline to 3.24 μV (95% CI 2.16-4.31; P = .015) and mean HR from 89 bpm (95% CI 80-98) at baseline to 83 bpm (95% CI 76-90; P = .007). Bilateral SG showed regions of decreased tyrosine hydroxylase staining with increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive nuclei in 18.47% (95% CI 9.68-46.62) of all ganglion cells, indicating cell death. Spontaneous PAT episodes were reduced from 9.83 per day (95% CI 5.77-13.89) in controls to 3.00 per day (95% CI 0.11-5.89) after ScNS (P = .027). Left lateral thoracic nerve ScNS also led to significant bilateral SG neuronal death and significantly reduced average SGNA and HR in dogs. CONCLUSION: ScNS at 2 different sites in the thorax led to SG cell death, reduced SGNA, and suppressed PAT in ambulatory dogs.Item Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts(American Heart Association, 2017-02) Yin, Dechun; Hsieh, Yu-Cheng; Tsai, Wei-Chung; Wu, Adonis Zhi-Yang; Jiang, Zhaolei; Chan, Yi-Hsin; Xu, Dongzhu; Yang, Na; Shen, Changyu; Chen, Zhenhui; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas H., IV; Medicine, School of MedicineBACKGROUND: Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (IKAS) are heterogeneously upregulated in failing hearts. We hypothesized that IKAS influences the location and stability of rotors during VF. METHODS AND RESULTS: Optical mapping was performed on 9 rabbit hearts with pacing-induced heart failure. The epicardial right ventricular and left ventricular surfaces were simultaneously mapped in a Langendorff preparation. At baseline and after apamin (100 nmol/L) infusion, the action potential duration (APD80) was determined, and VF was induced. Areas with a >50% increase in the maximum action potential duration (ΔAPD) after apamin infusion were considered to have a high IKAS distribution. At baseline, the distribution density of phase singularities during VF in high IKAS distribution areas was higher than in other areas (0.0035±0.0011 versus 0.0014±0.0010 phase singularities/pixel; P=0.004). In addition, high dominant frequencies also colocalized to high IKAS distribution areas (26.0 versus 17.9 Hz; P=0.003). These correlations were eliminated during VF after apamin infusion, as the number of phase singularities (17.2 versus 11.0; P=0.009) and dominant frequencies (22.1 versus 16.2 Hz; P=0.022) were all significantly decreased. In addition, reentrant spiral waves became unstable after apamin infusion, and the duration of VF decreased. CONCLUSIONS: The IKAS current influences the mechanism of VF in failing hearts as phase singularities, high dominant frequencies, and reentrant spiral waves all correlated to areas of high IKAS. Apamin eliminated this relationship and reduced VF vulnerability.Item Subcutaneous Nerve Stimulation Reduces Sympathetic Nerve Activity in Ambulatory Dogs with Myocardial Infarction(Elsevier, 2020-07) Yuan, Yuan; Zhao, Ye; Wong, Johnson; Tsai, Wei-Chung; Jiang, Zhaolei; Kabir, Ryan A.; Han, Seongwook; Shen, Changyu; Fishbein, Michael C.; Chen, Lan S.; Chen, Zhenhui; Everett, Thomas H., IV.; Chen, Peng-Sheng; Medicine, School of MedicineBackground: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting. Objective: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. Methods: In the experimental group, a radio transmitter was implanted during the first sterile surgery to record nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. Results: In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 μV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 μV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 μV (P<.039) and 2.14±0.50 μV (P<.001) at 4 and 8 weeks, respectively, after MI. In comparison, aSGNA at 4 and 8 weeks in dogs with MI but no ScNS was 8.26±6.31 μV (P=.005) and 10.82±7.86 μV (P=0002), respectively. Immunostaining showed confluent areas of remodeling in bilateral stellate ganglia and a high percentage of tyrosine hydroxylase-negative ganglion cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling was positive in 26.61%±11.54% of ganglion cells in the left stellate ganglion and 15.94%±3.62% of ganglion cells in the right stellate ganglion. Conclusion: ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac nerve sprouting after acute MI.Item Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs(Elsevier, 2015-06) Jiang, Zhaolei; Zhao, Ye; Doytchinova, Anisiia; Kamp, Nicholas J.; Tsai, Wei-Chung; Yuan, Yuan; Adams, David; Wagner, David; Shen, Changyu; Chen, Lan S.; Everett, Thomas H.; Lin, Shien-Fong; Chen, Peng-Sheng; Department of Medicine, IU School of MedicineBACKGROUND: 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 and is easily accessible. OBJECTIVE: The purpose of this study was 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 stellate ganglion abruptly increased both right SGNA and SKNA in 5 anesthetized dogs. We integrated nerve activities and averaged heart rate in each 1-minure window over 10 minutes. We implanted a radiotransmitter to record left SGNA in 4 ambulatory dogs (2 normal, 1 with myocardial infarction, 1 with intermittent rapid atrial pacing). After 2 weeks of recovery, we simultaneously recorded the SKNA and left SGNA continuously for 30 minutes when the dogs were ambulatory. RESULTS: There was a positive correlation [average r = 0.877, 95% confidence interval (CI) 0.732-1.000, P <.05 for each dog] between integrated skin nerve activity (iSKNA) and SGNA (iSGNA) and between iSKNA and heart rate (average r = 0.837, 95% CI 0.752-0.923, P <.05). Similar to that found in the anesthetized dogs, there was a positive correlation (average r = 0.746, 95% CI 0.527-0.964, P <.05) between iSKNA and iSGNA and between iSKNA and heart rate (average r = 0.706, 95% CI 0.484-0.927, P <.05). CONCLUSION: SKNAs can be used to estimate SGNA in dogs.