Browsing by Author "Yuan, Yuan"

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Antiarrhythmic effects of stimulating the left dorsal branch of the thoracic nerve in a canine model of paroxysmal atrial tachyarrhythmias
(2018-08-01)
Zhao, Ye
;
Yuan, Yuan
;
Tsai, Wei-Chung
;
Jiang, Zhaolei
;
Tian, Zhi-peng
BACKGROUND Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial tachyarrhythmia (PAT) episodes in dogs with intermittent rapid 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 PATs. METHODS We performed long-term 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 mu V (95% confidence interval [CI] 4.10-4.62 mu V) at baseline to 3.22 mu V (95% CI 3.04-3.40 mu V) after 2 weeks (P5.028) 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 rapid LA pacing. Histological studies in the 2 dogs without intermittent rapid LA pacing 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 and right stellate ganglia, reduces left SGNA, and is antiarrhythmic in this canine model of PAT.
Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs
(2017-02-01)
Tsai, Wei-Chung
;
Chan, Yi-Hsin
;
Chinda, Kroekkiat
;
Chen, Zhenhui
;
Patel, Jheel
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 mu V, 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.
Ganglionated plexi and ligament of Marshall ablation reduces atrial vulnerability and causes stellate ganglion remodeling in ambulatory dogs
(2016-10)
Zhao, Ye
;
Jiang, Zhaolei
;
Tsai, Wei-Chung
;
Yuan, Yuan
;
Chinda, Kroekkiat
BACKGROUND Simultaneous activation of the stellate ganglion (SG), the ligament of Marshall (LOM), and the ganglionated plexi often precedes the onset of paroxysmal atrial tachyarrhythmia (PAT). OBJECTIVE The purpose of this study was to test the hypothesis that ablation of the LOM and the superior left ganglionated plexi (SLGP) reduces atrial vulnerability and results in remodeling of the SG. METHODS Nerve activity was correlated to PAT and ventricular rate (VR) at baseline, after ablation of the LOM and SLGP, and after atrial fibrillation. Neuronal cell death was assessed with tyrosine hydroxylase 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 SG nerve activity and VR increased from 2.2 mu V (95% confidence interval [CI] 1.2-3.3 mu V) and 80 bpm (95% CI 68-92 bpm) at baseline, to 3.0 mu V (95% CI 2.6-3.4 mu V, P = .046) and 90 bpm (95% CI 75-108 bpm, P = .026) after ablation, and to 3.1 mu V (95% CI 1.7-4.5 mu V, P = .116) and 95 bpm (95% CI 79-110 bpm, P = .075) after atrial fibrillation. There was an increase in tyrosine hydroxylase negative cells in the ablation group and 19.7% (95% CI 8.6%-30.8%) TUN EL-positive staining in both the left and right SG. None were observed in the control group. CONCLUSION LOM and SLGP ablation caused left SG remodeling and cell death. There was reduced correlation of the VR response and PAT to SG nerve activity. These findings support the importance of SLGP and LOM in atrial arrhythmogenesis.
Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy
(2017-12-01)
Yuan, Yuan
;
Hassel, Jonathan L.
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Doytchinova, Anisiia
;
Adams, David
;
Wright, Keith C.
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 158672 seconds, with output of 1.9260.42 mA at 24.17 +/- 2.01 Hz. Average SKNA during VNS off-time was 1.06 mV (95% confidence interval [CI] 0.93-1.18) in lead I and 1.13 mV (95% CI 0.99-1.27) in lead II, which was significantly lower than 1.38 mV (95% CI 1.01-1.75; P = .036) and 1.38 mV (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
(2018-03-01)
Yuan, Yuan
;
Jiang, Zhaolei
;
Zhao, Ye
;
Tsai, Wei-Chung
;
Patel, Jheel
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 mV (95% confidence interval [ CI] 3.89-6.75) at baseline to 3.24 mV (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.
Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits
(2018-05-01)
Yin, Dechun
;
Chen, Mu
;
Yang, Na
;
Wu, Adonis Z.
;
Xu, Dongzhu
BACKGROUND Apamin-sensitive small conductance calcium-activated K current (I-KAS) is up-regulated during ventricular pacing and masks short-term cardiac memory (CM). OBJECTIVE The purpose of this study was to determine the role of I-KAS in long-term CM. METHODS CM was created with 3-5 weeks of ventricular pacing and defined by a flat or inverted T wave off pacing. Epicardial optical mapping was performed in both paced and normal ventricles. Action potential duration (APD(80)) was determined during right atrial pacing. Ventricular stability was tested before and after I-KAS blockade. Four paced hearts and 4 normal hearts were used for western blotting and histology. RESULTS There were no significant differences in either echocardiographic parameters or fibrosis levels between groups. Apamin induced more APD(80) prolongation in CM than in normal ventricles (mean [95% confidence interval]: 9.6% [8.8%-10.5%] vs 3.1% [1.9%-4.3%]; P <.001). Apamin significantly lengthened APD(80) in the CM model at late activation sites, indicating significant I-KAS up-regulation at those sites. The CM model also had altered Ca2+ handling, with the 50% Ca2+ transient duration and amplitude increased at distal sites compared to a proximal site (near the pacing site). After apamin, the CM model had increased ventricular fibrillation (VF) inducibility (paced vs control: 33/40 (82.5%) vs 7/20 (35%); P < .001) and longer VF durations (124 vs 26 seconds; P < .001). CONCLUSION Chronic ventricular pacing increases Ca2+ transients at late activation sites, which activates I-KAS to maintain repolarization reserve. I-KAS blockade increases VF vulnerability in chronically paced rabbit ventricles.
Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram
(2017-01)
Doytchinova, Anisiia
;
Hassel, Jonathan L.
;
Yuan, Yuan
;
Lin, Hongbo
;
Yin, Dechun
BACKGROUND Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 +/- 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P <.001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 +/- 0.14, P <.05) and shortening of QT interval (P <.001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.
Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs
(2015-06-01)
Jiang, Zhaolei
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Zhao, Ye
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Doytchinova, Anisiia
;
Kamp, Nicholas J.
;
Tsai, Wei-Chung
BACKGROUND 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.