Daniela Lucini

Conversion From Vagal to Sympathetic Predominance With Strenuous Training in High-Performance World Class Athletes

Background—Benefits of moderate endurance training include increases in parasympathetic activity and baroreflex sensitivity (BRS) and a relative decrease in sympathetic tone. However, the effect of very intensive training load on neural cardiovascular regulation is not known. We tested the hypothesis that strenuous endurance training, like in high-performance athletes, would enhance sympathetic activation and reduce vagal inhibition. Methods and Results—We studied the entire Italian junior national team of rowing (n=7) at increasing training loads up to 75% and 100% of maximum, the latter ∼20 days before the Rowing World Championship. Autoregressive power spectral analysis was used to investigate RR interval and blood pressure (BP) variabilities. BRS was assessed by the sequences method. Increasing training load up to 75% of maximum was associated with a progressive resting bradycardia and increased indexes of cardiac vagal modulation and BRS. However, at 100% training load these effects were reversed, with increases in resting heart rate, diastolic BP, low-frequency RR interval, and BP variabilities and decreases in high-frequency RR variability and BRS. Three athletes later won medals in the World Championship. Conclusions—This study indicates that very intensive endurance training shifted the cardiovascular autonomic modulation from a parasympathetic toward a sympathetic predominance. This finding should be interpreted within the context of the substantial role played by the sympathetic nervous system in increasing cardiovascular performance at peak training. Whether the altered BP and autonomic function shown in this study might be in time hazardous to human cardiovascular system remains to be established.

Impact of chronic psychosocial stress on autonomic cardiovascular regulation in otherwise healthy subjects

Elevated psychosocial stress might favor the occurrence of cardiovascular disease; however, mechanisms are incompletely understood. We hypothesized that patients (n=126; 44±1 years of age) referred to an internal medicine clinic because of symptoms related to chronic psychosocial stress would demonstrate signs of autonomic dysregulation compared with controls (n=132; 42±1 years of age). We used autoregressive spectral analysis of RR interval variability to obtain indirect markers of sympathetic and of vagal (respectively, low-frequency and high-frequency components, both expressed in normalized units) oscillatory modulation of sinoatrial node, as well as of sympathetic vasomotor regulation (low-frequency component of systolic arterial pressure variability) and of cardiac baroreflex sensitivity (&agr;-index). Higher values of systolic and diastolic arterial pressure (respectively, 124±1 versus 117±1 mm Hg and 80±1 versus 75±1 mm Hg; both P<0.001), altered markers of autonomic regulation (increased normalized low-frequency and reduced high-frequency component of RR variability, P<0.005; increased-low frequency component of systolic arterial pressure variability, P<0.002), and reduced baroreflex sensitivity (19.3±1.4 versus 23.0±2.0 ms/mm Hg; P<0.05) were observed in patients compared with controls. Autonomic responses to active standing were also blunted in stressed patients. Autonomic markers were significantly correlated to stress perception score and were capable of discriminating between controls and patients with a high degree of accuracy. Chronic real-life stress in humans appears associated to increased arterial pressure and to impaired autonomic regulation of cardiovascular functions. The combination of sympathetic predominance, vagal withdrawal, and blunted baroreflex sensitivity might represent a treatable mechanistic link between psychosocial factors and future incidence of hypertension.

Impairment in Cardiac Autonomic Regulation Preceding Arterial Hypertension in Humans Insights From Spectral Analysis of Beat-by-Beat Cardiovascular Variability

Background—Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels. Methods and Results—We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and &agr;-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis–derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group. Conclusions—RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.

Autonomic dysregulation in essential hypertension: insight from heart rate and arterial pressure variability

Essential hypertension is the most prevalent cardiovascular disorder, affecting more than 50 million people in the USA. Hypertension-related mortality and morbidity figures have been greatly improved over the last three decades by major advances in prevention. Detection and operative suggestions for practicing physicians are available from several guideline treatments derived from grouped data obtained in numerous well-conducted studies on large numbers of patients. However, the disappointing results of some forms of antihypertensive therapies, particularly in preventing coronary artery disease, has shed some doubts on traditional approaches to managing hypertensive patients. At present, in spite of extensive investigations, the exact causal mechanism(s) are far from being fully understood, and consequently, essential hypertension is still managed using a heuristic approach. Persistent elevations in arterial pressure imply some disturbances in the complex and multifactorial cardiovascular control mechanisms. In this context, neurohumoral disturbances might play a special role, in view of the demonstration that an elevated sympathetic drive seems essential in hypertensive patients. In this review, we follow the hypothesis that other allied methods capable of quantitatively assessing some aspects of the regulatory system might support and integrate the usual dichotomous diagnostic procedure based on arterial pressure determinations. In prior studies, we reported that parameters obtained by spectral analysis of heart rate variability (HRV) might furnish useful information on autonomic normal and abnormal nervous system regulation. In the foregoing, we summarize our experience using this approach in the clinical management of hypertensive patients. It is our tenet that spectral analysis of mono or multivariate cardiovascular beat-by-beat variabilities provides potentially important information on alterations in neural control of the circulation accompanying essential hypertension. In spite of an ongoing debate on the interpretation of specific aspects of HRV spectral components, overall, it appears that the available evidence supports the hypothesis that in essential hypertension, there is an increased sympathetic and reduced vagal cardiac drive coupled with an enhancement of vasomotor sympathetic modulation. Prospective studies on large populations, rendered more easy to perform, thanks to improvements in technology and telemedicine applications, might provide an answer to the still open question of how to apply spectral analysis of HRV to a better mechanistic understanding of essential hypertension, and to more satisfactory individually tailored antihypertensive treatments.

A controlled study of the autonomic changes produced by habitual cigarette smoking in healthy subjects

OBJECTIVES An increased sympathetic drive, in view of its proarrhythmic, proatherosclerotic, and prothrombotic actions, could contribute to the elevated cardiovascular risk of habitual smokers. However, the underlying mechanisms are still debated. In this study we address the hypothesis that spectral analysis of RR interval and systolic arterial pressure short-term variabilities may be used to assess the complex autonomic changes produced by habitual cigarette smoking. METHODS A cross-sectional design compared heavy (> 20 cigarettes/day) habitual smokers (n = 20; 40 +/- 3 years), with similar age controls. Spectral analysis of RR interval variability provided markers of the sympatho-vagal balance modulating the SA node, by way of the normalised low frequency (LF approximately equal to 0.10 Hz) and high frequency (HF approximately equal to 0.25 Hz) components. The LF component of systolic arterial pressure (SAP) variability assessed the sympathetic vasomotor modulation. The frequency domain index (alpha) measured the baroreflex gain of the SA node. Subjects were studied at rest, and during the sympathetic excitation produced by active standing. RESULTS In smokers LFRR was, at rest, greater than in controls (70.6 +/- 3.8 vs 46.0 +/- 2.5 normalised units, nu); concurrently HFRR was reduced (22.1 +/- 3.2 vs 42.0 +/- 2.8 nu). Baroreflex gain and RR variance were also smaller in smokers. LFSAP was, instead, similar in the smokers and control groups. The standing induced increase in LFRR was blunted (P < 0.001) in smokers. CONCLUSIONS Spectral analysis of RR interval and systolic arterial pressure variability indicates that habitual cigarette smoking induces selective alterations in neural control of the SA node. An increase at rest in markers of sympathetic modulation is accompanied by signs of reduced vagal drive and depressed baroreflex gain; while sympathetic vasomotor modulation appears similar in controls and smokers. Data are consistent with the hypothesis that autonomic alterations may contribute to the increased cardiovascular risk present in smokers.

Individual Recognition by Heart Rate Variability of Two Different Autonomic Profiles Related to Posture

BACKGROUND Power spectrum analysis of heart rate variability (HRV) can estimate the state of sympathovagal balance modulating sinus node activity. In view of the large distribution of spectral variables, a recognition of well-defined physiological conditions has never been attempted on an individual basis. METHODS AND RESULTS We considered 10 spectral variables extracted from short segments (200 to 500 cardiac cycles) of 350 ECG tracings recorded in normal subjects in both supine and upright positions (700 patterns). The tracings were first ordered consecutively and subsequently assigned alternatively to a training or to a test set (each consisting of 175 cases, providing 350 patterns considered to be independent). A forecasting linear method estimated a normalized activation index (ranging from -1 for supine to +1 for upright) that concentrated the information derived from spectral variables and that identified, in the test set, individual by individual, approximately 84% of corresponding body postures. CONCLUSIONS The combined use of spectral methodology and forecasting analysis has revealed an information content embedded, per se, in a short series of RR intervals capable of recognizing, individual by individual, two different autonomic profiles related to posture.

Stress Management at the Worksite: Reversal of Symptoms Profile and Cardiovascular Dysregulation

Work stress may increase cardiovascular risk either indirectly, by inducing unhealthy life styles, or directly, by affecting the autonomic nervous system and arterial pressure. We hypothesized that, before any apparent sign of disease, work-related stress is already accompanied by alterations of RR variability profile and that a simple onsite stress management program based on cognitive restructuring and relaxation training could reduce the level of stress symptoms, revert stress-related autonomic nervous system dysregulation, and lower arterial pressure. We compared 91 white-collar workers, enrolled at a time of work downsizing (hence, in a stress condition), with 79 healthy control subjects. Psychological profiles were assessed by questionnaires and autonomic nervous system regulation by spectral analysis of RR variability. We also tested a simple onsite stress management program (cognitive restructuring and relaxation training) in a subgroup of workers compared with a sham subgroup (sham program). Workers presented an elevated level of stress-related symptoms and an altered variability profile as compared with control subjects (low-frequency component of RR variability was, respectively, 65.2±2 versus 55.3±2 normalized units; P<0.001; opposite changes were observed for the high-frequency component). These alterations were largely reverted (low-frequency component of RR variability from 63.6±3.9 to 49.3±3 normalized units; P<0.001) by the stress management program, which also slightly lowered systolic arterial pressure. No changes were observed in the sham program group. This noninvasive study indicates that work stress is associated with unpleasant symptoms and with an altered autonomic profile and suggests that a stress management program could be implemented at the worksite, with possible preventive advantages for hypertension.

Effects of aging and of chronic obstructive pulmonary disease on RR interval variability

Clinical and experimental investigations suggest that spectral analysis of RR interval variability might be employed to assess changes in autonomic regulation of the SA node occurring in various chronic, cardiac or respiratory conditions. We studied three groups of subjects: young healthy, older healthy, and old patients with chronic obstructive pulmonary disease (COPD), considering RR interval and breathing, i.e. tidal volume, variability in the frequency domain (AR algorithms), in order to obtain markers of the sympathetic and vagal modulation of the SA node [by way, respectively, of the low (LF) and high frequency (HF) spectral components]. The gain of the relationship between tidal volume and heart period variation (index beta) was also examined. COPD patients demonstrated a reduced resting RR variance with maintained spectral power distribution; upon tilting they did not manifest the usual increase of LF (and attendant decrease of HF) component. Additionally, we observed that the index beta at rest was significantly reduced in older as opposed to younger subjects. This index was also reduced by tilt, in both groups. In patients the index beta was reduced as compared to the group of similar age and younger subjects, and did not diminish further with tilt. This study indicates that in patients with COPD, sympathetic excitatory modulation of the SA node is depressed. Furthermore, the index beta, which provides an assessment of the gain of respiratory modulation of RR interval variability is significantly reduced in patients, as compared to healthy subjects of similar age. These abnormalities of autonomic control, may represent a functional correlation of the hyperinflated state present in this clinical condition which can be assessed non-invasively with spectral analysis of RR interval and respiration.

A controlled study of the effects of mental relaxation on autonomic excitatory responses in healthy subjects

Objective Circumstantial evidence indicates that, in the presence of a suitable substratum, sudden, behaviorally induced increases in sympathetic drive to the cardiovascular system might play an important physiopathological role in various conditions, ranging from arterial hypertension to sudden coronary death. Accordingly, it might be useful to study the effects of behavioral interventions, such as mental relaxation, that might be capable of blunting excitatory autonomic responses. It would also be preferable to study healthy subjects in whom autonomic control is not modified by the presence of disease, and to use noninvasive approaches to minimize the possible emotional impact produced by invasive recordings. Methods We examined healthy subjects who were either subjected to relaxation training (N = 13) or sham relaxation (N = 12). An additional group, treated with beta-adrenergic blockade (N = 12), was also examined. Spectral and cross-spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided quantitative markers of sympathovagal balance modulating the sinoatrial (SA) node, of sympathetic vasomotor modulation, and of the gain of the arterial pressure/heart period baroreflex (index alpha). Subjects were studied at rest, during standing, and during mental arithmetic. Results Data indicate that both beta-adrenergic blockade and relaxation training significantly blunted the excitatory autonomic responses to standing and to mental arithmetic. Indices of sympathetic modulation also seemed reduced by beta blockade at rest. No changes were observed with sham training. Conclusions Frequency domain analysis of cardiovascular variabilities, using a totally noninvasive approach, indicates that relaxation training significantly blunts the excitatory autonomic changes produced by standardized behavioral laboratory stimuli.

Large Artery Remodeling and Dynamics following Simulated Microgravity by Prolonged Head-Down Tilt Bed Rest in Humans

The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA) after prolonged head-down tilt bed rest (HDTBR). Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI). Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT), resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.