Paolo Pizzinelli

Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

In 57 normal subjects (age 20–60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90° upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) β-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at ∼0.25 Hz and a low frequency at ∼0.1 Hz, with a normalized low frequency: high frequency ratio of 3.6 ± 0.7. With tilt, the low-frequency component became largely predominant (90 ± 1%) withalow frequency: high frequency ratio of 21 ± 4. Acute β-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency: high frequency ratio induced by tilt. Chronic β-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency: high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency: high frequency ratio (0.7 ± 0.1); during tilt, the increase in the low frequency: high frequency ratio (8.3 ± 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency: high frequency ratio at rest of 2.8 ± 0.7, which became 17 ± 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation. Bilateral stellectomy prevented this low-frequency increase in R-R but not in arterial pressure autospectra, indicating that sympathetic nerves to the heart are instrumental in the genesis of low-frequency oscillations in R-R interval.

Spectral analysis of r-r and arterial pressure variabilities to assess sympatho-vagal interaction during mental stress in humans

We tested the hypothesis that spectral analysis of the R-R interval and systolic arterial pressure variabilities allows assessment of the dynamic changes in neural control of the cardiovascular system in men undergoing mental stress testing. Mental arithmetic increased the low-frequency components of R-R and systolic arterial pressure, i.e. markers of sympathetic activity to the SA node and the vasculature, respectively; it also decreased the high frequency component of R-R variability, a marker of vagal activity. Spectral analysis of R-R and systolic arterial pressure variabilities may be used in the clinic to test the dynamic effects of mental stress on both sympathetic and vagal activities.

Muscle metaboreflex contribution to sinus node regulation during static exercise: insights from spectral analysis of heart rate variability.

BACKGROUND It is currently assumed that during static exercise, central command increases heart rate (HR) through a decrease in parasympathetic activity, whereas the muscle metaboreflex raises blood pressure (BP) only through an increase in sympathetic outflow to blood vessels, because when the metaboreflex activation is maintained during postexercise muscle ischemia, BP remains elevated while HR recovers. We tested the hypotheses that the muscle metaboreflex contributes to HR regulation during static exercise via sympathetic activation and that the arterial baroreflex is involved in the HR recovery of postexercise muscle ischemia. METHODS AND RESULTS Eleven healthy male volunteers performed 4-minute static leg extension (SLE) at 30% of maximal voluntary contraction, followed by 4-minute arrested leg circulation (ALC). Autonomic regulation of HR was investigated by spectral analysis of HR variability (HRV), and baroreflex control of heart period was assessed by the spontaneous baroreflex method. SLE resulted in a significant increase in the low-frequency component of HRV that remained elevated during ALC. The normalized high-frequency component of HRV was reduced during SLE and returned to control levels during ALC. Baroreflex sensitivity was significantly reduced during SLE and returned to control levels during ALC when BP was kept elevated above the resting level while HR recovered. CONCLUSIONS The muscle metaboreflex contributes to HR regulation during static exercise via a sympathetic activation. The bradycardia that occurs during postexercise muscle ischemia despite the maintained sympathetic stimulus may be explained by a baroreflex-mediated increase in parasympathetic outflow to the sinoatrial node that overpowers the metaboreflex-induced cardiac sympathetic activation.

Assessment of the neural control of the circulation during psychological stress

In this study, we used spectral analysis of short-term R-R and systolic arterial pressure (SAP) variabilities to estimate the changes in neural control of the circulation produced by psychological stress. The 0.1 Hz low-frequency (LF) component of R-R and SAP variabilities provided a quantitative index of the sympathetic activity controlling heart rate and vasomotion. Conversely the high-frequency (HF) respiratory component of R-R variability provided an index of vagal tone. In conscious dogs we used the seemingly stressful situation of being accompanied for the first time to the experimental laboratory as a stimulus. In human subjects we used mental arithmetic. In both cases LF of R-R and SAP variabilities increased significantly suggesting enhanced sympathetic activity both to the SA node and the vasculature. In man, the index alpha, a measure of the overall gain of baroreceptor mechanisms, was found to be reduced during mental arithmetic. Spectral analysis of cardiovascular variabilities thus suggests that in man and in conscious dogs psychological challenges induce a profound re-arrangement of neural control of the circulation, which appears to be characterised by sympathetic predominance and which can be monitored by this technique.

A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.

The role of pressor sympathetic reflexes in circulatory control was investigated in conscious dogs. Animals were previously instrumented with a 6- to 8-cm rigid core cannula covered by an inflatable rubber cylinder in the thoracic aorta, a pressure catheter implanted in the aorta above the cannula, and a second catheter inserted into the aorta below the cannula through a femoral artery. Two piezoelectric crystals were positioned at opposing adventitial sites to measure aortic distension with ultrasound techniques. After recovery from surgery, the diameter of the aortic segment surrounding the cannula was increased by 9.6 ± 0.4% from 16 ± 1 mm by inflating the rubber cylinder, without obstructing blood flow. Mean aortic pressure rose 31 ± 3% from 100 ± 3 mm Hg and heart rate 20 ± 3% from 91 ± 3 beats/min (P < 0.01). The pressor response was abolished by α-adrenergic blockade (phentolamine 1 mg/kg, iv). The heart rate response was reduced either by β-blockade (propranolol 1 mg/kg, iv) or muscarinic blockade (atropine 0.2 mg/kg, iv) and abolished by their combination. During aortic stretch, the sensitivity of the baroreflex was reduced 57 ± 7% from 18 ± 2 msec/mm Hg (P < 0.01). The pressor response was increased to 49 ± 8% after bilateral carotid sinus nerve section and vagotomy. These excitatory reflex responses were obtained in absence of any pain reaction. Thus, in the conscious dog, aortic distension within physiological ranges induces a potent pressor sympathetic reflex with positive feedback characteristics. Such a pressor reflex not only occurs in the presence of functioning baroreflexes, but is also capable of reducing their sensitivity.

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.

Hemodynamic, autonomic and baroreflex changes after one night sleep deprivation in healthy volunteers

BACKGROUND Sleep disorders are associated to a number of cardiovascular disturbances that might increase cardiovascular risk. Sleep deprivation, in particular, might, by inducing autonomic dysregulation, raise arterial pressure and hypertensive risk. Available evidence however is contradictory. METHODS We tested the main hypothesis that one night sleep deprivation in 24 volunteers might alter hemodynamics (heart rate and Arterial Pressure - AP), autonomic regulation (mono and bivariate spectral analysis of RR and non invasive AP variability) and baroreflex control (spectral index alpha and spontaneous baroreflex slope), performance indices (reaction time) and subjective stress (questionnaires and salivary cortisol). Volunteers were studied in normal living conditions and while kept in isolation and confinement, to test the presence of possible bias related to environmental stress. RESULTS Results indicate that there were no differences between normal living conditions and isolation and confinement (Intraclass Correlation Coefficient >0.75 for most variables). Conversely, after one night sleep deprivation subjects felt tired (p<0.05), and performance deteriorated (p<0.05), while cortisol profile was substantially maintained, hemodynamic parameters did not change and HRV and index alpha increased slightly. CONCLUSIONS Findings support the contention that one night sleep deprivation, in absence of significant additional stress or disturbances, does not lead to increased arterial pressure values or to changes in autonomic or baroreflex profiles that could conceivably favor hypertension development, but induces the expected increase in tiredness and reduction in performance.

Cardiovascular reflexes mediated by sympathetic afferent fibers.

In this paper the experimental evidence supporting the hypothesis that excitatory sympathetic reflexes may participate in the tonic control of the cardiovascular system is discussed. Positive feedback pressor sympathetic reflexes can be obtained with physiological distensions of the descending thoracic aorta in conscious dogs with all nerves intact in absence of any pain reaction. These excitatory reflexes interact with supraspinal regulatory mechanisms, inhibitory in nature. A massive excitation of cardiac sympathetic afferents, produced by intracoronary injections of bradykinin, also elicits a pressor reflex, without pain reactions. In the absence of anesthesia and recent surgery, the cardiovascular excitatory reflexes, subserved by sympathetic afferent fibers, can easily prevail. We suggest that negative and positive feedback mechanisms interact continuously to achieve the most adequate neural cardiovascular control.

Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS‐107 of the space shuttle Columbia

One of the most important features of prolonged weightlessness is a progressive impairment of muscular function with a consequent decrease in exercise capacity. We tested the hypothesis that the impairment in musculo‐skeletal function that occurs in microgravity results in a potentiation of the muscle metaboreflex mechanism and also affects baroreflex modulation of heart rate (HR) during exercise. Four astronauts participating in the 16 day Columbia shuttle mission (STS‐107) were studied 72–71 days before launch and on days 12–13 in‐flight. The protocol consisted of 6 min bicycle exercise at 50% of individual followed by 4 min of postexercise leg circulatory occlusion (PECO). At rest, systolic (S) and diastolic (D) blood pressure (BP), R‐R interval and baroreflex sensitivity (BRS) did not differ significantly between pre‐ and in‐flight measurements. Both pre‐ and in‐flight, SBP increased and R‐R interval and BRS decreased during exercise, whereas DBP did not change. During PECO preflight, SBP and DBP were higher than at rest, whereas R‐R interval and BRS recovered to resting levels. During PECO in‐flight, SBP and DBP were significantly higher whereas R‐R interval and BRS remained significantly lower than at rest. The part of the SBP response (Δ) that was maintained by PECO was significantly greater during spaceflight than before (34.5 ± 8.8 versus 13.8 ± 11.9 mmHg, P= 0.03). The tachycardic response to PECO was also significantly greater during spaceflight than preflight (−141.5 ± 25.2 versus−90.5 ± 33.3 ms, P= 0.02). This study suggests that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.