Browsing by Author "Liu, Xiao"

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    Effects of anesthetic and sedative agents on sympathetic nerve activity
    (Elsevier, 2019) Liu, Xiao; Rabin, Perry Lee; Yuan, Yuan; Kumar, Awaneesh; Vasallo, Peter, III; Wong, Johnson; Mitscher, Gloria A.; Everett, Thomas H., IV; Chen, Peng-Sheng; Medicine, School of Medicine
    Background The effects of sedative and anesthetic agents on sympathetic nerve activity (SNA) are poorly understood. Objective The purpose of this study was to determine the effects of commonly used sedative and anesthetic agents on SNA in ambulatory dogs and humans. Methods We implanted radiotransmitters in 6 dogs to record stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (ScNA), and blood pressure (BP). After recovery, we injected dexmedetomidine (3 μg/kg), morphine (0.1 mg/kg), hydromorphone (0.05 mg/kg), and midazolam (0.1 mg/kg) on different days. We also studied 12 human patients (10 male; age 68.0 ± 9.1 years old) undergoing cardioversion for atrial fibrillation with propofol (0.77 ± 0.18 mg/kg) or methohexital (0.65 mg/kg) anesthesia. Skin sympathetic nerve activity (SKNA) and electrocardiogram were recorded during the study. Results SGNA and ScNA were significantly suppressed immediately after administration of dexmedetomidine (P = .000 and P = .000, respectively), morphine (P = .011 and P = .014, respectively), and hydromorphone (P = .000 and P = .012, respectively), along with decreased BP and heart rate (HR) (P <.001 for each). Midazolam had no significant effect on SGNA and ScNA (P = .248 and P = .149, respectively) but increased HR (P = .015) and decreased BP (P = .004) in ambulatory dogs. In patients undergoing cardioversion, bolus propofol administration significantly suppressed SKNA (from 1.11 ± 0.25 μV to 0.77 ± 0.15 μV; P = .001), and the effects lasted for at least 10 minutes after the final cardioversion shock. Methohexital decreased chest SKNA from 1.59 ± 0.45 μV to 1.22 ± 0.58 μV (P = .000) and arm SKNA from 0.76 ± 0.43 μV to 0.55 ± 0.07 μV (P = .001). The effects lasted for at least 10 minutes after the cardioversion shock. Conclusion Propofol, methohexital, dexmedetomidine, morphine, and hydromorphone suppressed, but midazolam had no significant effects on, SNA.
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    Skin sympathetic nerve activity and nocturnal blood pressure non-dipping in patients with postural orthostatic tachycardia syndrome
    (Wolters Kluwer, 2023) Liu, Xiao; Rosenberg, Carine; Reaso, Jewel N.; Lee, Andrew M.; Ricafrente, Joselyn; Ebinger, Joseph E.; Chen, Lan S.; Li, Xiaochun; Merz, C. Noel Bairey; Rader, Florian; Chen, Peng-Sheng; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Objective: Postural orthostatic tachycardia syndrome (POTS) is associated with abnormal blood pressure (BP) regulation and increased prevalence of nocturnal nondipping. We hypothesized that nocturnal nondipping of BP is associated with elevated skin sympathetic nerve activity (SKNA) in POTS. Method: We used an ambulatory monitor to record SKNA and electrocardiogram from 79 participants with POTS (36 ± 11 years, 72 women), including 67 with simultaneous 24-h ambulatory BP monitoring. Results: Nocturnal nondipping of BP was present in 19 of 67 (28%) participants. The nondipping group had a higher average SKNA (aSKNA) from midnight of day 1 to 0100 h on day 2 than the dipping group ( P = 0.016, P = 0.030, respectively). The differences (Δ) of aSKNA and mean BP between daytime and night-time were more significant in the dipping group compared with the nondipping group (ΔaSKNA 0.160 ± 0.103 vs. 0.095 ± 0.099 μV, P = 0.021, and Δmean BP 15.0 ± 5.2 vs. 4.9 ± 4.2 mmHg, P < 0.001, respectively). There were positive correlations between ΔaSKNA and standing norepinephrine (NE) (r = 0.421, P = 0.013) and the differences between standing and supine NE levels ( r = 0.411, P = 0.016). There were 53 (79%) patients with SBP less than 90 mmHg and 61 patients (91%) with DBP less than 60 mmHg. These hypotensive episodes were associated with aSKNA of 0.936 ± 0.081 and 0.936 ± 0.080 μV, respectively, which were both significantly lower than the nonhypotensive aSKNA (1.034 ± 0.087 μV, P < 0.001 for both) in the same patient. Conclusion: POTS patients with nocturnal nondipping have elevated nocturnal sympathetic tone and blunted reduction of SKNA between day and night. Hypotensive episodes were associated with reduced aSKNA.
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    Skin Sympathetic Nerve Activity as a Biomarker of Fitness
    (Elsevier, 2021) Liu, Xiao; Kumar, Awaneesh; O’Neil, Joseph; Wong, Johnson; Saadoon, Osama; Kadire, Siri; Mitscher, Gloria A.; Li, Xiaochun; Chen, Peng-Sheng; Emery, Michael S.; Everett, Thomas H., IV; Biostatistics, School of Public Health
    Background: Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention. Objective: The purpose of this study was to test the hypothesis that noninvasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels. Methods: Oxygen consumption (VO2) and SKNA were recorded in 39 patients undergoing an incremental exercise test. Patients were grouped by 5 levels of fitness based on age, sex, and VO2max. Results: With exercise, all patients had a significant increase in average SKNA (aSKNA) (1.58 ± 1.12 μV to 4.50 ± 3.06 μV, P = .000) and heart rate (HR) (87.40 ± 20.42 bpm to 154.13 ± 16.82 bpm, P = .000). A mixed linear model of aSKNA was used with fixed effects of fitness, exercise time, and recovery time, and random effects of subject level intercept and slopes for exercise time and recovery times. The poor fitness group had significantly higher aSKNA than the other groups (P = .0273). For all subjects studied, aSKNA increased by 5% per minute with progression of exercise and decreased by 15% per minute with progression of recovery. The fitness variable encodes information on both comorbidities and body mass index (BMI). Once fitness level is known, comorbidities and BMI are not significantly associated with aSKNA. In all groups, aSKNA positively correlated with HR (R2 = 0.47 ± 0.23) and VO2 (R2 = 0.68 ± 0.25). Conclusion: Fitness level determines the magnitude and time course of SKNA increase during exercise. SKNA may be a useful fitness biomarker in exercise stress testing.
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    Skin sympathetic nerve activity in patients with chronic orthostatic intolerance
    (Elsevier, 2022) Lee, Andrew; Liu, Xiao; Rosenberg, Carine; Borle, Sanjana; Hwang, Daerin; Chen, Lan S.; Li, Xiaochun; Merz, Noel Bairey; Chen, C. Peng-Sheng; Biostatistics and Health Data Science, School of Medicine
    Background: Chronic orthostatic intolerance (OI) is characterized by the development of tachycardia and other symptoms when assuming an upright body position. Objective: The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. Methods: We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or β-blockers. Results: In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptoms had higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomatic in controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). Conclusion: SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.
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    Subcutaneous nerve stimulation for rate control in ambulatory dogs with persistent atrial fibrillation
    (Elsevier, 2019-09-01) Yuan, Yuan; Liu, Xiao; Wan, Juyi; Wong, Johnson; Bedwell, Amanda A.; Persohn, Scott A.; Shen, Changyu; Fishbein, Michael C.; Chen, Lan S.; Chen, Zhenhui; Everett, Thomas H.; Territo, Paul R.; Chen, Peng-Sheng; Medicine, School of Medicine
    Background: Subcutaneous nerve stimulation (ScNS) damages the stellate ganglion and improves rhythm control of atrial fibrillation (AF) in ambulatory dogs. Objective: To test the hypothesis that thoracic ScNS can improve rate control in persistent AF. Methods: We created persistent AF in 13 dogs and randomly assigned them to ScNS (N=6) and sham control groups (N=7). 18F-2-Fluoro-2-deoxyglucose (18F-FDG) positron emission tomography / magnetic resonance imaging of the brain stem was performed at baseline and at the end of the study. Results: The average stellate ganglion nerve activity (aSGNA) reduced from 4.00±1.68 μV after the induction of persistent AF to 1.72±0.42 μV (p=0.032) after ScNS. In contrast, the aSGNA increased from 3.01±1.26 μV during AF to 5.52±2.69 μV after sham stimulation (p=0.023). The mean ventricular rate during persistent AF reduced from 149±36 bpm to 84±16 bpm (p=0.011) in ScNS group but no changes were observed in control. Left ventricular ejection fraction (LVEF) remained unchanged in ScNS group but reduced significantly in sham control group. Immunostaining showed damaged ganglion cells in bilateral stellate ganglia and increased brain stem glial cell reaction in the ScNS group but not in the controls. The 18F-FDG uptake in pons and medulla was significantly (p=0.011) higher in the ScNS group than the sham control group at the end of the study. Conclusions: Thoracic ScNS causes neural remodeling in the brain stem and stellate ganglia, controls the ventricular rate and preserves the LVEF in ambulatory dogs with persistent AF.
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    Subcutaneous nerve stimulation for rate control in ambulatory dogs with persistent atrial fibrillation
    (Elsevier, 2019) Yuan, Yuan; Liu, Xiao; Wan, Juyi; Wong, Johnson; Bedwell, Amanda A.; Persohn, Scott A.; Shen, Changyu; Fishbein, Michael C.; Chen, Lan S.; Chen, Zhenhui; Everett, Thomas H., IV; Territo, Paul R.; Chen, Peng-Sheng; Medicine, School of Medicine
    Background Subcutaneous nerve stimulation (ScNS) damages the stellate ganglion and improves rhythm control of atrial fibrillation (AF) in ambulatory dogs. Objective The purpose of this study was to test the hypothesis that thoracic ScNS can improve rate control in persistent AF. Methods We created persistent AF in 13 dogs and randomly assigned them to ScNS (n = 6) and sham control (n = 7) groups. 18F-2-Fluoro-2-deoxyglucose positron emission tomography/magnetic resonance imaging of the brain stem was performed at baseline and at the end of the study. Results The average stellate ganglion nerve activity reduced from 4.00 ± 1.68 μV after the induction of persistent AF to 1.72 ± 0.42 μV (P = .032) after ScNS. In contrast, the average stellate ganglion nerve activity increased from 3.01 ± 1.26 μV during AF to 5.52 ± 2.69 μV after sham stimulation (P = .023). The mean ventricular rate during persistent AF reduced from 149 ± 36 to 84 ± 16 beats/min (P = .011) in the ScNS group, but no changes were observed in the sham control group. The left ventricular ejection fraction remained unchanged in the ScNS group but reduced significantly in the sham control group. Immunostaining showed damaged ganglion cells in bilateral stellate ganglia and increased brain stem glial cell reaction in the ScNS group but not in the control group. The 18F-2-fluoro-2-deoxyglucose uptake in the pons and medulla was significantly (P = .011) higher in the ScNS group than the sham control group at the end of the study. Conclusion Thoracic ScNS causes neural remodeling in the brain stem and stellate ganglia, controls the ventricular rate, and preserves the left ventricular ejection fraction in ambulatory dogs with persistent AF.
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    Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea
    (Elsevier, 2022) Meng, Guannan; He, Wenbo; Wong, Johnson; Li, Xiaochun; Mitscher, Gloria A.; Adams, David; Everett, Thomas H., IV; Manchanda, Shalini; Liu, Xiao; Chen, Peng-Sheng; Tang, Yuzhu; Medicine, School of Medicine
    Background: Obstructive sleep apnea (OSA) is associated with cardiovascular diseases and increased sympathetic tone. We previously demonstrated that patients with OSA have increased skin sympathetic nerve activity (SKNA). Objective: The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA. Methods: The electrocardiogram, SKNA, and polysomnographic recording were recorded simultaneously in 9 patients with OSA. After baseline recording, CPAP titration was performed and the pressure was adjusted gradually for the optimal treatment, defined by reducing the apnea-hypopnea index (AHI) to ≤5/h. Otherwise the treatment was considered suboptimal (AHI > 5/h). Fast Fourier transform analyses were performed to investigate the frequency spectrum of SKNA. Results: There were very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations in SKNA. The HF oscillation matched the frequency of respiration. OSA episodes were more frequently associated with the VLF and LF than with the HF oscillations of SKNA. Compared with baseline, CPAP significantly decreased the arousal index and AHI and increased the minimal and mean oxyhemoglobin levels. Optimal treatment significantly increased the dominant frequency and reduced the heart rate, average SKNA (aSKNA), SKNA burst duration, and total burst area. The dominant frequency negatively correlated with aSKNA. Conclusion: VLF, LF, and HF oscillations are observed in human SKNA recordings. Among them, VLF and LF oscillations are associated with OSA while HF oscillations are associated with normal breathing. CPAP therapy reduces aSKNA and shifts the frequency of SKNA oscillation from VLF or LF to HF.
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    Testosterone does not shorten action potential duration in Langendorff perfused rabbit ventricles
    (Elsevier, 2023-10) Ueoka, Akira; Sung, Yen-Ling; Liu, Xiao; Rosenberg, Carine; Chen, Zhenhui; Everett, Thomas H, IV; Rubart, Michael; Tisdale, James E.; Chen, Peng-Sheng; Pediatrics, School of Medicine
    Background: Women have longer baseline QT intervals than men. Because previous studies showed that testosterone and 5α-dihydrotestosterone shorten the ventricular action potential duration (APD) in animal models, differential testosterone concentrations may account for the sex differences in QT interval. Objective: The purpose of this study was to test the hypothesis that testosterone shortens the APD in Langendorff-perfused rabbit ventricles. Methods: We performed optical mapping studies in hearts with or without testosterone administration. Acute studies included 26 hearts using 2 different protocols, including 17 without and 9 with atrioventricular (AV) block. For chronic studies, we implanted testosterone pellets subcutaneously in 7 female rabbits for 2-3 weeks before optical mapping studies during complete AV block. Six rabbits without pellet implantation served as controls. Results: The hearts in the acute studies were paced with a pacing cycle length (PCL) of 200-300 ms and mapped at baseline and after administration of 1 nM, 10 nM, 100 nM, and 3 μM of testosterone. There was no shortening of APD80 at any PCL. Instead, a lengthening of APD80 was noted at higher concentrations. There were no sex differences in testosterone responses. In chronic studies, heart rates were 136 ± 5 bpm before and 148 ± 9 bpm after (P = .10) while QTc intervals were 314 ± 9 ms before and 317 ± 99 ms after (P = .69) testosterone pellet implantation, respectively. Overall, ventricular APD80 in the pellet group was longer than in the control group at 300- to 700-ms PCL. Conclusion: Testosterone does not shorten ventricular repolarization in rabbit hearts.
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    Using an ambulatory electrocardiogram monitor to record skin sympathetic nerve activity
    (Elsevier, 2022) Liu, Xiao; Rosenberg, Carine; Ricafrente, Joselyn; Leier, Mary E.; Dinh, Harrison; Everett, Thomas H., IV; Chen, Peng-Sheng; Medicine, School of Medicine