IU Indianapolis ScholarWorks :: Browsing by Author "Chen, Lan S."

Browsing by Author "Chen, Lan S."

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Cervical vagal nerve stimulation activates the stellate ganglion in ambulatory dogs
(Synapse, 2015-03-24) Rhee, Kyoung-Suk; Hsueh, Chia-Hsiang; Hellyer, Jessica A.; Park, Hyung Wook; Lee, Young Soo; Garlie, Jason; Onkka, Patrick; Doytchinova, Anisiia T.; Garner, John B.; Patel, Jheel; Chen, Lan S.; Fishbein, Michael C.; Everett 4th, Thomas; Lin, Shien-Fong; Chen, Peng-Sheng; Department of Neurology, IU School of Medicine
BACKGROUND AND OBJECTIVES: Recent studies showed that, in addition to parasympathetic nerves, cervical vagal nerves contained significant sympathetic nerves. We hypothesized that cervical vagal nerve stimulation (VNS) may capture the sympathetic nerves within the vagal nerve and activate the stellate ganglion. MATERIALS AND METHODS: We recorded left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA), and subcutaneous electrocardiogram in seven dogs during left cervical VNS with 30 seconds on-time and 30 seconds off time. We then compared the SGNA between VNS on and off times. RESULTS: Cervical VNS at moderate (0.75 mA) output induced large SGNA, elevated heart rate (HR), and reduced HR variability, suggesting sympathetic activation. Further increase of the VNS output to >1.5 mA increased SGNA but did not significantly increase the HR, suggesting simultaneous sympathetic and parasympathetic activation. The differences of integrated SGNA and integrated VNA between VNS on and off times (ΔSGNA) increased progressively from 5.2 mV-s {95% confidence interval (CI): 1.25-9.06, p=0.018, n=7} at 1.0 mA to 13.7 mV-s (CI: 5.97-21.43, p=0.005, n=7) at 1.5 mA. The difference in HR (ΔHR, bpm) between on and off times was 5.8 bpm (CI: 0.28-11.29, p=0.042, n=7) at 1.0 mA and 5.3 bpm (CI 1.92 to 12.61, p=0.122, n=7) at 1.5 mA. CONCLUSION: Intermittent cervical VNS may selectively capture the sympathetic components of the vagal nerve and excite the stellate ganglion at moderate output. Increasing the output may result in simultaneously sympathetic and parasympathetic capture.
Chronic Low-Level Vagus Nerve Stimulation Reduces Stellate Ganglion Nerve Activity and Paroxysmal Atrial Tachyarrhythmias in Ambulatory Canines
(Office of the Vice Chancellor for Research, 2011-04-08) Shen, Mark J.; Shinohara, Tetsuji; Park, Hyung-Wook; Frick, Kyle; Ice, Daniel S.; Choi, Eue-Keun; Han, Seongwook; Sharma, Rahul; Shen, Changyu; Fishbein, Michael C.; Chen, Lan S.; Lopshire, John C.; Zipes, Douglas P.; Lin, Shien-Fong; Chen, Peng-Sheng
Introduction: Left sided low-level vagus nerve stimulation (LL-VNS) is used clinically for epilepsy and depression. We hypothesize that LL-VNS can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. Methods: We implanted in 12 dogs a neurostimulator in left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activities (SGNA), left thoracic vagal nerve activities (VNA) and electrocardiograms. The first 6 dogs (Group 1) underwent 1 week continuous LL-VNS. Another 6 dogs (Group 2) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Results: Integrated SGNA was significantly reduced during LL-VNS (7.8±0.9 mV-s vs. 9.4±0.9 mVs at baseline, P<0.05) in Group 1.The reduction was most apparent from 7 to 9 AM, (31% reduction, 10.8±2.5 mV-s versus 15.6±2.9 mV-s at baseline, P<0.01), along with a significantly reduced heart rate (P<0.05). SGNA-induced heart rate acceleration averaged 107.9±9.0 bpm during LL-VNS and 129.2±9.3 bpm at baseline (P<0.05). LL-VNS did not change VNA. The tyrosine hydroxylase-positive nerve structures in the left stellate ganglion were 99,684±22,257 µm2/mm2 in LL-VNS dogs and 186,561±11,383 µm2/mm2 (P<0.01) in normal control dogs. In Group 2, the frequencies of paroxysmal atrial fibrillation and atrial tachycardia during active LLVNS were 1.4±2.5/d and 8.0±5.8/d, respectively, significantly lower than during sham stimulation (9.2±6.2/d, P<0.01 and 22.0±4.4/d, P<0.001, respectively). Conclusion: LL-VNS suppresses SGNA and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident one week after cessation of chronic LL-VNS.
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 Medicine
BACKGROUND: 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.
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 Medicine
OBJECTIVES: 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.
Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs
(Elsevier, 2016-03) Chinda, Kroekkiat; Tsai, Wei-Chung; Chan, Yi-Hsin; Lin, Andrew Y.-T.; Patel, Jheel; Zhao, Ye; Tan, Alex Y.; Shen, Mark J.; Lin, Hongbo; Shen, Changyu; Chattipakorn, Nipon; Rubart-von der Lohe, Michael; Chen, Lan S.; Fishbein, Michael C.; Lin, Shien-Fong; Chen, Zhenhui; Chen, Peng-Sheng; Department of Medicine, IU School of Medicine
BACKGROUND: The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. METHODS: We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. RESULTS: We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P = .021) and 115 beats/min (95% CI 96-134 beats/min; P = .016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P = .037) and 114 beats/min (95% CI 83-146 beats/min; P = .039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. CONCLUSION: VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.
Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy
(Elsevier, 2017-12) Yuan, Yuan; Hassel, Jonathan L.; Doytchinova, Anisiia; Adams, David; Wright, Keith C.; Meshberger, Chad; Chen, Lan S.; Guerra, Maria P.; Shen, Changyu; Lin, Shien-Fong; Everett IV, Thomas H.; Salanova, Vincenta; Chen, Peng-Sheng; Neurology, School of Medicine
BACKGROUND: We recently reported that skin sympathetic nerve activity (SKNA) can be used to estimate sympathetic tone in humans. In animal models, vagal nerve stimulation (VNS) can damage the stellate ganglion, reduce stellate ganglion nerve activity, and suppress cardiac arrhythmia. Whether VNS can suppress sympathetic tone in humans remains unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that VNS suppresses SKNA in patients with drug-resistant epilepsy. METHODS: ECG patch electrodes were used to continuously record SKNA in 26 patients with drug-resistant epilepsy who were admitted for video electroencephalographic monitoring. Among them, 6 (2 men, age 40 ± 11 years) were previously treated with VNS and 20 (7 men, age 37 ± 8 years) were not. The signals from ECG leads I and II were filtered to detect SKNA. RESULTS: VNS had an on-time of 30 seconds and off-time of 158 ± 72 seconds, with output of 1.92 ± 0.42 mA at 24.17 ± 2.01 Hz. Average SKNA during VNS off-time was 1.06 μV (95% confidence interval [CI] 0.93-1.18) in lead I and 1.13 μV (95% CI 0.99-1.27) in lead II, which was significantly lower than 1.38 μV (95% CI 1.01-1.75; P = .036) and 1.38 μV (95% CI 0.98-1.78; P = .035) in the control group, respectively. Heart rate was 65 bpm (95% CI 59-71) in the VNS group, which was significantly lower than 77 bpm (95% CI 71-83) in the control group. CONCLUSION: Patients with VNS had significantly lower SKNA than those without VNS.
Left Cervical Vagal Nerve Stimulation Reduces Skin Sympathetic Nerve Activity in Patients with Drug Resistant Epilepsy
(Elsevier, 2017) Yuan, Yuan; Hassel, Jonathan L.; Doytchinova, Anisiia; Adams, David; Wright, Keith C.; Meshberger, Chad; Chen, Lan S.; Guerra, Maria P.; Shen, Changyu; Lin, Shien-Fong; Everett, Thomas H., IV; Salanova, Vicenta; Chen, Peng-Sheng; Department of Medicine, School of Medicine
Background We recently reported that skin sympathetic nerve activity (SKNA) can be used to estimate sympathetic tone in humans. In animal models, vagal nerve stimulation (VNS) can damage the stellate ganglion, reduce stellate ganglion nerve activity, and suppress cardiac arrhythmia. Whether VNS can suppress sympathetic tone in humans remains unclear. Objective The purpose of this study was to test the hypothesis that VNS suppresses SKNA in patients with drug-resistant epilepsy. Methods ECG patch electrodes were used to continuously record SKNA in 26 patients with drug-resistant epilepsy who were admitted for video electroencephalographic monitoring. Among them, 6 (2 men, age 40 ± 11 years) were previously treated with VNS and 20 (7 men, age 37 ± 8 years) were not. The signals from ECG leads I and II were filtered to detect SKNA. Results VNS had an on-time of 30 seconds and off-time of 158 ± 72 seconds, with output of 1.92 ± 0.42 mA at 24.17 ± 2.01 Hz. Average SKNA during VNS off-time was 1.06 μV (95% confidence interval [CI] 0.93–1.18) in lead I and 1.13 μV (95% CI 0.99–1.27) in lead II, which was significantly lower than 1.38 μV (95% CI 1.01–1.75; P = .036) and 1.38 μV (95% CI 0.98–1.78; P = .035) in the control group, respectively. Heart rate was 65 bpm (95% CI 59–71) in the VNS group, which was significantly lower than 77 bpm (95% CI 71–83) in the control group. Conclusion Patients with VNS had significantly lower SKNA than those without VNS.
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 Medicine
BACKGROUND: 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.
Myocardial Repolarization Dispersion and Autonomic Nerve Activity in a Canine Experimental Acute Myocardial Infarction Model
(Elsevier, 2014-01) Piccirillo, Gianfranco; Moscucci, Federica; D’Alessandro, Gaetana; Pascucci, Matteo; Rossi, Pietro; Han, Seongwook; Chen, Lan S.; Lin, Shien-Fong; Chen, Peng-Sheng; Magrì, Damiano; Department of Neurology, IU School of Medicine
Background Evidence from a canine experimental acute myocardial infarction (MI) model shows that until the seventh week after MI the relationship between stellate ganglionic nerve and vagal nerve activities (SGNA/VNA) progressively increases. Objective We evaluated how autonomic nervous system activity influences temporal myocardial repolarization dispersion at this period. Methods We analyzed autonomic nerve activity as well as QT and RR variability from recordings previously obtained in 9 dogs. From a total 48 short-term electrocardiographic segments, 24 recorded before and 24 seven weeks after experimentally-induced MI, we obtained three indices of temporal myocardial repolarization dispersion: QTe (from q wave T to wave end), QTp (from q wave to T wave peak) and Te (from T wave peak to T wave end) variability index (QTeVI, QTpVI, TeVI). We also performed a heart rate variability power spectral analysis on the same segments. Results After MI, all the QT variables increased QTeVI (median [interquartile range]) (from - 1.76[0.82] to −1.32[0.68]), QTeVI (from −1.90[1.01] to −1.45[0.78]) and TeVI (from −0.72[0.67] to −0.22[1.00]), whereas all RR spectral indexes decreased (p<0.001 for all). Distinct circadian rhythms in QTeVI (p<0.05,) QTpVI (p<0.001) and TeVI (p<0.05) appeared after MI with circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI acrophase coincided with another SGNA/VNA peak. After MI, regression analysis detected a positive relationship between SGNA/VNA and TeVI (R2: 0.077; β: 0.278; p< 0.001). Conclusion Temporal myocardial repolarization dispersion shows a circadian variation after MI reaching its peak at a time when sympathetic is highest and vagal activity lowest.
Role of the Autonomic Nervous System in Atrial Fibrillation: Pathophysiology and Therapy
(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-04-25) Chen, Peng-Sheng; Chen, Lan S.; Fishbein, Michael C.; Lin, Shien-Fong; Nattel, Stanley; Department of Medicine, IU School of Medicine
Autonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia (AT) and atrial fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review we focus on the relationship between the autonomic nervous system and the pathophysiology of AF, and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches and biological therapies. While the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.

Browsing by Author "Chen, Lan S."

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