Clinical Autonomic Research

Lower aerobic fitness increases the risk of developing hypertension. Muscle sympathetic nerve activity (MSNA) is important for the beat-by-beat regulation of blood pressure. Whether the cardiovascular consequences of lower aerobic fitness are due to augmented transduction of MSNA into vascular responses is unclear. We tested the hypothesis that aerobic fitness is inversely related to peak increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) in response to spontaneous MSNA bursts in young males. Relative peak oxygen consumption (VO2peak, indirect calorimetry) was assessed in 18 young males (23 ± 3 years; 41 ± 8 ml/kg/min). MSNA (microneurography), cardiac intervals (electrocardiogram) and arterial pressure (finger photoplethysmography) were recorded continuously during supine rest. Stroke volume and cardiac output (CO) were estimated via the ModelFlow method. TPR was calculated as MAP/CO. Changes in TPR and MAP were tracked for 12 cardiac cycles following heartbeats associated with or without spontaneous bursts of MSNA. Overall, aerobic fitness was inversely correlated to the peak ΔTPR (0.8 ± 0.7 mmHg/l/min; R = − 0.61, P = 0.007) and ΔMAP (2.3 ± 0.8 mmHg; R = − 0.69, P < 0.001), but not with the peak ΔCO (0.2 ± 0.1 l/min; P = 0.50), MSNA burst frequency (14 ± 5 bursts/min; P = 0.43) or MSNA relative burst amplitude (65 ± 12%; P = 0.13). Heartbeats without an associated burst of MSNA did not increase TPR, MAP or CO. Although unrelated to traditional MSNA characteristics, aerobic fitness was inversely associated with spontaneous sympathetic neurovascular transduction in young males. This may be a potential mechanism by which aerobic fitness modulates the regulation of arterial blood pressure through the sympathetic nervous system.

In order to characterize the autonomic profile of syncopal children, we have studied heart rate variability (HRV) of 73 children, ages 11–18, with neurocardiogenic syncope and a positive outcome of head-up tilt testing (HUT).HRV was calculated over a 24-hour period for the time-domain indices (SDNN, SDANNi, SDNN, rMSSD, pNN50), and over 5-minute segments from night and day for frequency-domain indices (LF, HF, LF/HF). The obtained results were compared to reference values calculated for Polish children. 55% of the children had mixed response to HUT, 41% vasodepressor and 4% cardioinhibitory. Patients with syncope had significantly lower values of rMSSD and pNN50 in comparison to healthy children. Moreover, in the frequency-domain analysis they exhibited significantly higher LF and lower HF values. The day-night rhythm of HRV and the age-related changes of HRV were, however, similar in syncopal and healthy children. In addition to this, we found a significantly lower SDNN value in children with cardioinhibitory response during HUT in comparison to children with mixed response. We concluded that 1) based on HRV analysis children with neurocardiogenic syncope had alterations in basal autonomic balance, which indicated an increased sympathetic modulation in these patients, 2) syncopal children had adequate circadian rhythm of autonomic activity, 3) the changes of HRV indices with age in these groups are not altered in comparison to healthy children, 4) syncopal children may exhibit differences in HRV indices values depending on the kind of vasovagal response observed during HUT.

To determine normal values for pupillometry indices in healthy control subjects and to examine these indices in patients with autonomic dysfunction and healthy controls. Infrared video pupillometry was used to investigate the pupil response to a brief light flash in 79 healthy controls, 28 patients with normal autonomic function (composite autonomic severity score, CASS < 2), and 26 patients with moderate to severe autonomic failure (CASS > 4) seen in our autonomic laboratory from January 2008 to June 2011. In six subjects, we examined the effects of varying light stimulus intensity and light stimulus duration. Descriptive analysis, correlation, and ANCOVA adjusted for age were performed. We determined eight indices corresponding to parasympathetic and sympathetic pupil function. Baseline pupil diameter (BPD), maximum constriction velocity (MCV), absolute constriction amplitude (ACA), and maximum dilation velocity (MDV) negatively correlated with age (p < 0.01) among controls. MCV and ACA increased with increasing intensity of light stimulus from 3.5 to 112 μW. Indices of parasympathetic pupil innervation (MCV and ACA) were lower in the high CASS group compared to others (p < 0.0001). Indices of sympathetic pupil function, time to reach 75 % of initial resting diameter during pupillary dilation (T¾), and dilation velocity at T¾ (DV¾) did not differ significantly in the three study groups. However, T¾ corrected for the magnitude of pupillary constriction (T¾:ACA) was higher in the high CASS group suggesting sympathetic dysfunction in that group (p = 0.0003). Indices of pupillomotor function significantly differ between patients with moderate to severe autonomic failure and healthy controls.

Baroreceptor sensitivity (BRS) is increasingly used as a prognostic indicator in cardiovascular disease. Traditionally it has been measured using invasive techniques with pharmacological manipulation of blood pressure (BP). With the advent of newer methods to measure pulse interval and beat-to-beat changes in BP it is now possible, using sophisticated mathematical modelling techniques, to calculate cardiac BRS non-invasively. However, there are virtually no data on the reproducibility of these newer techniques and what factors may affect the repeatability of these measurements. We studied 39 subjects, aged 22–82 years, with a supine systolic BP range 97–160 mmHg and a diastolic BP range 57–94 mmHg on two occasions between 1 week and 6 months apart. Cardiac BRS was measured by power spectral analysis using Fast Fourier Transformation (FFT), sequence analysis (using up, down and combined sequences) and from phase IV of the Valsalva manoeuvre. There was no significant difference between visits for any of the methods for measuring cardiac BRS. Mean BRS values were similar for FFT (16.7±11.2 ms/mmHg) and sequence analysis (15.8±11.4 ms/mmHg); however, results using phase IV of the Valsalva manoeuvre were significantly lower (8.1±2.9 ms/mmHg,p<0.0001). The coefficient of variation for the five measures of cardiac BRS varied from 16.8% for Valsalva-derived values to 26.1% for ‘down’ sequence analysis. However, in ten subjects BRS could not be calculated from the Valsalva manoeuvre. None of the independent variables tested (including age, BP levels and time between testing) significantly influenced the degree of repeatability. In summary, there appears to be little difference between these non-invasive methods in their degree of reproducibility. These techniques would seem suitable for longitudinal studies of changes in cardiac BRS and overcome many of the problems associated with the invasive pharmacological methods.

Wide variations in respiratory rate and hypoxic stimulation of chemoreceptors may produce unreliable autonomic results in patients with COPD. We studied the reproducibility of two consecutive measurements of heart rate variability (HRV) and blood pressure variability (BPV) by time frequency analysis in patients with COPD while controlling respiratory rate and oxygen hemoglobin saturation (SaO2). Reproducibility was assessed by paired t-tests and correlation analyses between repeated measures. Correlation analyses of the log transformed low (LF) and high frequency (HF) HRV were x̄ 11.5 ± 1.1 in measurement A and x̄ 11.5 ± 1.0 in measurement B (r = 0.89, p < 0.0001), and x̄ 10.5 ± 1.1 in measurement A and x̄ 10.6 ± 1.1 in measurement B (r = 0.89, p < 0.0001) respectively. The log transformed LF and HF BPV were x̄ 4.9 ± 1.3 in measurement A and x̄ 5.3 ± 0.9 in measurement B (r = 0.70, p < 0.0002), and x̄ 6.4 ± 1.3 in measurement A and 6.6 ± 1.2 in measurement B (R = 0.71 p < 0.0001) respectively. In conclusion, time frequency analysis of HRV and BPV is reproducible and reliable in patients with COPD while controlling their respiratory rate and oxygen hemoglobin saturation. Reproducibility of these measurements may allow for a non-invasive evaluation of autonomic tone in response to treatments in COPD patients.