Browsing by Author "Wright, Keith C."

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    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.
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    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.
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    Skin Sympathetic Nerve Activity as a Biomarker for Neurological Recovery during Therapeutic Hypothermia for Cardiac Arrest
    (Elsevier, 2021) Kutkut, Issa; Uceda, Domingo; Kumar, Awaneesh; Wong, Johnson; Li, Xiaochun; Wright, Keith C.; Straka, Susan; Adams, David; Deckard, Michelle; Kovacs, Richard; Chen, Peng-Sheng; Everett, Thomas H., IV.; Medicine, School of Medicine
    Background: Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed. Objective: The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status. Methods: SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome. Results: Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013). Conclusion: Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.
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    Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation
    (Elsevier, 2017) Uradu, Andrea; Wan, Juyi; Doytchinova, Anisiia; Wright, Keith C.; Lin, Andrew Y. T.; Chen, Lan S.; Shen, Changyu; Lin, Shien-Fong; Everett, Thomas H., IV; Chen, Peng-Sheng; Department of Medicine, IU School of Medicine
    Background Skin sympathetic nerve activity (SKNA) is useful for estimating sympathetic tone in humans. Objective The purpose of this study was to test the hypotheses that (1) increased SKNA is associated with the onset and termination of paroxysmal atrial tachycardia (AT) and atrial fibrillation (AF) and (2) sinoatrial node response to SKNA is reduced in patients with more frequent AT or AF episodes. Methods SKNA and electrocardiogram were recorded in 11 patients (4 men and 7 women; average age 66 ± 10 years), including 3 patients with AT (11 ± 18 episodes per patient) and 8 patients with AF (24 ± 26 episodes per patient). Results The average SKNA (aSKNA) 10 seconds before AT onset was 1.07 ± 0.10 μV and 10 seconds after termination was 1.27 ± 0.10 μV; both were significantly (P = .032 and P < .0001) higher than that during sinus rhythm (0.97 ± 0.09 μV). The aSKNA 10 seconds before AF onset was 1.34 ± 0.07 μV and 10 seconds after termination was 1.31 ± 0.07 μV; both were significantly (P < .0001) higher than that during sinus rhythm (1.04 ± 0.07 μV). The aSKNA before onset (P < .0001) and after termination (P = .0011) was higher in AF than in AT. The sinus rate correlated (P < .0001) with aSKNA in each patient (average r = 0.74; 95% confidence interval 0.65–0.84). The r value in each patient negatively correlated with the number of AT and AF episodes (r = −0.6493; 95% confidence interval −0.8990 to −0.08073; P = .0306). Conclusion Increased SKNA was observed both at the onset and termination of AT and AF. Patients with more frequent AT and AF episodes had a weak correlation between sinus rate and aSKNA, suggesting sinoatrial node remodeling by tachycardia.
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    Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment
    (SpringerNature, 2016-12-14) Yang, Jin; Savvatis, Konstantinos; Kang, Jong Seok; Fan, Peidong; Zhong, Hongyan; Schwartz, Karen; Barry, Vivian; Mikels-Vigdal, Amanda; Karpinski, Serge; Kornyeyev, Dmytro; Adamkewicz, Joanne; Feng, Xuhui; Zhou, Qiong; Shang, Ching; Kumar, Praveen; Phan, Dillon; Kasner, Mario; Lopez, Begona; Diez, Javier; Wright, Keith C.; Kovacs, Roxanne L.; Chen, Peng-Sheng; Quertermous, Thomas; Smith, Victoria; Yao, Lina; Tschope, Carsten; Chang, Ching-Pin; Department of Medicine, IU School of Medicine
    Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.