Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy.

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.

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram.

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 (V1-V6) 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.

Reassessing Risk Factors for High Defibrillation Threshold: The EF-SAGA Risk Score and Implications for Device Testing.

OBJECTIVES: To reevaluate risk factors for high defibrillation threshold (DFT) and propose a risk assessment tool. BACKGROUND: Controversy exists over routine DFT testing during implantable cardioverter defibrillator (ICD) placement. METHODS: We retrospectively analyzed 1,642 consecutive patients who received an ICD and underwent DFT testing. RESULTS: The incidence of high DFT requiring addition of a subcutaneous array was 2.3%. Five significant independent variables predictive of high DFT were identified, including younger age, male gender (hazard ratio 1.99), left ventricular (LV) dysfunction, secondary prevention (hazard ratio 2.33), and amiodarone use (hazard ratio 2.39). Each 10-year increase in age was indicative of a 0.35-times lower chance of high DFT. Each 10% increase of LV ejection fraction (EF) was indicative of a 0.52-times lower chance of high DFT. These five variables form the EF-SAGA risk score (LVEF < 20%, Secondary prevention ICD indication, Age < 60 years, male Gender, Amiodarone use). Cumulative risk of high DFT increased incrementally; patients with four or more variables had an 8.9% likelihood of high DFT. Importantly, primary prevention patients with LVEF > 20% had a negative predictive value for high DFT of 99.3%. CONCLUSION: We identified five independent predictors of high DFT. We propose the EF-SAGA risk score to help decision making. Primary prevention patients with an LVEF > 20% had an exceedingly low incidence of high DFT suggesting that testing could be avoided in these patients. Careful assessment of the risk-benefit ratio of testing is important in high-risk patients.

Suppression of food intake by glucagon-like peptide-1 receptor agonists: relative potencies and role of dipeptidyl peptidase-4.

Administration of the glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1 and exendin-4 (Ex-4) directly into the central nervous system decreases food intake. But although Ex-4 potently suppresses food intake after peripheral administration, the effects of parenteral GLP-1 are variable and not as strong. A plausible explanation for these effects is the rapid inactivation of circulating GLP-1 by dipeptidyl peptidase-4 (DPP-4), an enzyme that does not alter Ex-4 activity. To test this hypothesis, we assessed the relative potency of Ex-4 and GLP-1 under conditions in which DPP-4 activity was reduced. Outbred rats, wild-type mice, and mice with a targeted deletion of DPP-4 (Dpp4(-/-)) were treated with GLP-1 alone or in combination with the DPP-4 inhibitor vildagliptin, Ex-4, or saline, and food intake was measured. GLP-1 alone, even at high doses, did not affect feeding in wild-type mice or rats but did reduce food intake when combined with vildagliptin or given to Dpp4(-/-) mice. Despite plasma clearance similar to DPP-4-protected GLP-1, equimolar Ex-4 caused greater anorexia than vildagliptin plus GLP-1. To determine whether supraphysiological levels of endogenous GLP-1 would suppress food intake if protected from DPP-4, rats with Roux-en-Y gastric bypass and significantly elevated postprandial plasma GLP-1 received vildagliptin or saline. Despite 5-fold greater postprandial GLP-1 in these animals, vildagliptin did not affect food intake in Roux-en-Y gastric bypass rats. Thus, in both mice and rats, peripheral GLP-1 reduces food intake significantly less than Ex-4, even when protected from DPP-4. These findings suggest distinct potencies of GLP-1 receptor agonists on food intake that cannot be explained by plasma pharmacokinetics.