Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea.

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.

Skin sympathetic nerve activity as a biomarker of fitness.

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.

Skin sympathetic nerve activity in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiac arrhythmia and sudden cardiac death. We recently developed a new method (neuECG) to noninvasively measure electrocardiogram and skin sympathetic nerve activity (SKNA). OBJECTIVE: The purpose of this study was to test the hypothesis that SKNA measured during sleep study is higher in patients with OSA than in those without OSA. METHODS: We prospectively recorded neuECG and polysomnography in 26 patients undergoing a sleep study. Sleep stages were scored into rapid eye movement (REM), and non-REM sleep stages 1 (N1), 2 (N2), and 3 (N3). Average voltage of skin sympathetic nerve activity (aSKNA) and SKNA burst area were calculated for quantification. Apnea/hypopnea index (AHI) >5 per hour was used to diagnose OSA. RESULTS: There was a positive correlation (r = 0.549; P = .018) between SKNA burst area and the arousal index in OSA but not in the control group. aSKNA during sleep was 0.61 ± 0.09 µV in OSA patients (n = 18) and 0.53 ± 0.04 µV in control patients (n = 8; P = .025). Burst area was 3.26 (1.90-4.47) µV·s/min in OSA patients and 1.31 (0.67-1.94) µV·s/min in control (P = .047). More apparent differences were found during N2, when the burst area in OSA (3.06 [1.46-5.52] µV·s/min) was much higher than that of the control (0.89 [0.79-1.65] µV·s/min; P = .03). CONCLUSION: OSA patients have higher SKNA activity than control patients, with the most pronounced differences observed during N2. Arousal at the end of apnea episodes is associated with large SKNA bursts. Overlaps of aSKNA and SKNA burst area between groups suggest that not all OSA patients have increased sympathetic tone.

Effects of anesthetic and sedative agents on sympathetic nerve activity.

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.