Global versus local linear beat-to-beat analysis of the relationship between arterial pressure and pulse transit time during dynamic exercise.

Global linear analysis has been traditionally performed to verify the relationship between pulse transit time (PTT) and systolic arterial pressure (SAP) at the level of their spontaneous beat-to-beat variabilities: PTT and SAP have been plotted in the plane (PTT,SAP) and a significant linear correlation has been found. However, this relationship is weak and in specific individuals cannot be found. This result prevents the utilization of the SAP-PTT relationship to derive arterial pressure changes from PTT measures on an individual basis. We propose a local linear approach to study the SAP-PTT relationship. This approach is based on the definition of short SAP-PTT sequences characterized by SAP increase (decrease) and PTT decrease (increase) and on their search in the SAP and PTT beat-to-beat series. This local approach was applied to PTT and SAP series derived from 13 healthy humans during incremental supine dynamic exercise (at 10, 20 and 30% of the nominal individual maximum effort) and compared to the global approach. While global approach failed in some subjects, local analysis allowed the extraction of the gain of the SAP-PTT relationship in all subjects both at rest and during exercise. When both local and global analyses were successful, the local SAP-PTT gain is more negative than the global one as a likely result of noise reduction.

Selective impairment of excitatory pressor responses after prolonged simulated microgravity in humans.

The haemodynamic and autonomic effects of prolonged exposure to simulated microgravity were assessed non-invasively in seven healthy volunteers completing a 42-day -6 degrees head down tilt. Before, during and after head down tilt, subjects were exposed to moderate excitatory stimuli (mental arithmetic and static handgrip) to gauge possible progressive impairment of pressor responses. Before and after head down tilt, subjects were also exposed to orthostatic stress, to assess influences of simulated microgravity on orthostatic defence. Simple haemodynamics (heart rate and systolic arterial blood pressure), linear (i.e., oscillatory) components of beat-by-beat variability, non-linear properties (i.e., corrected conditional entropy (CCE)) of RR interval variability, and baroreflex slope furnished a non-invasive evaluation of autonomic regulatory mechanisms. Pressor responses to mental arithmetic and to handgrip were markedly impaired after 42 days head down tilt, whereas responses in markers of autonomic regulation were not modified. Standing, performed 8 days after head down tilt to limit the risk of syncope, still induced a variable degree of hypotension, with signs of progressively greater sympathetic activation than before head down tilt. Simulated microgravity-induced reduction of pressor responses, in spite of largely maintained autonomic activation, favours the hypothesis of a peripheral impairment of cardiovascular homeostasis. rights reserved.

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.

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.

Adaptational changes in the neural control of cardiorespiratory function in a confined environment: the CNEC#3 experiment.

The goal of the study was to characterize the changes in neurovegetative control of the circulation, attending the presumed physiological and psychological stress originated by the isolation and confinement typical of the living condition of space stations, as simulated in a ground based unit, using time and frequency domain analysis. As a secondary goal we sought to verify the implementation of real time data acquisition, for off line spectral analysis of R-R interval, systolic arterial pressure (by Finapres) and respiration (by PVF2 piezoelectric sensors). We addressed the cardiorespiratory and neurovegetative responses to standardized, simple stressors (active standing, dynamic and static handgrip) on the EXEMSI 92 crew, before, during and after the isolation period. On average the appropriate excitatory responses (to stand, dynamic and static handgrip) were elicited also in isolation and confinement. Active standing and small masses muscular exercises are easy to be performed in a confined and isolated environment and provide a valuable tool for investigating the adaptational changes in neural control mechanisms. The possibility there exists of using this time and frequency domain approach to monitor the level of performance and well being of the space crew in (quasi) real time.

[The effects of chronic cilazapril treatment on sympathetic vasomotor tonus: a spectral analysis study of pressure variability]. / Effetti del trattamento cronico con cilazapril sul tono vasomotorio simpatico: studio con analisi spettrale della variabilità pressoria.

Animal experiments suggest that an important component of the antihypertensive effects of ACE inhibitors might derive from an inhibition of the sympathetic vasomotor tone. We addressed this problem on 22 mildly hypertensive subjects (48 +/- 2 years; arterial pressure 151 +/- 3/95 +/- 1 mmHg), in whom sympathetic vasomotor tone was non invasively inferred by the power of the low frequency component (0.1 Hz) of the spontaneous oscillations of systolic arterial pressure (LFSAP), during placebo and after 4 weeks of treatment with a new ACE inhibitor, cilazapril, 5 mg per os oid. LFSAP was computed at rest and during physical (active orthostatism) and mental (computerized attentional test and mental arithmetic) stimuli capable of enhancing sympathetic drive. Cilazapril treatment reduced resting arterial pressure to 128 +/- 3/80 +/- 2 mmHg, without affecting heart rate (78 +/- 2 and 74 +/- 2 b/min, respectively). The increases in LFSAP produced by standing were significantly greater during placebo than during active treatment (delta LFSAP = 10 +/- 3 and 5 +/- 2 mmHg2, respectively). These data suggest that an important reduction of sympathetic vasomotor tone accompanies the antihypertensive effects of chronic ACE-inhibitor treatment.

[A noninvasive assessment of the gain in baroceptor control of the heart rate in man]. / Valutazione noninvasiva del guadagno del controllo barocettivo della frequenza cardiaca nell'uomo.

In this study we addressed the problem of the noninvasive evaluation of the overall gain of baroreceptor control of heart period. We studied a population of healthy controls (n = 49, age 30 +/- 2 years, systolic arterial pressure [by Finapres] 114 +/- 1 mmHg) and a group of mild hypertensive subjects (n = 14, age 51 +/- 2 years, systolic arterial pressure 151 +/- 5 mmHg). Subjects were studied at rest both in absence and in presence of chronic beta-adrenergic receptor blockade (atenolol: controls 50 mg po oid x 4 days; hypertensives 100 mg po oid x 2 weeks). Spectral analysis of RR interval and of systolic arterial pressure variabilities provided noninvasive markers of autonomic control of the SA node and of the vasculature. The index alpha, obtained from bivariate cross spectral and spectral analysis provided a quantitative assessment of the closed loop gain of baroreceptor control of the heart period. The index alpha resulted more elevated in the normotensive than in the hypertensive group. Additionally it appeared significantly increased at the end of the treatment with the beta-adrenergic blocking drug atenolol. Furthermore, alpha appeared significantly and negatively correlated with age, systolic arterial pressure and, although weakly, with low frequency; it was positively correlated with the average RR interval. In conclusion, this study suggested an important link between the average level of sympathetic activity and baroreceptor control of heart rate in normotensive and mild hypertensive subjects. The clinical importance of this sympathetic modulation of the gain of the heart period/arterial pressure relationship can now be assessed with this noninvasive approach.

Effects of chronic cilazapril treatment on cardiovascular control: a spectral analytical approach.

In 11 subjects with mild hypertension (sitting arterial pressure of 146 +/- 5/97 +/- 2 mm Hg), the effects of chronic angiotensin-converting enzyme (ACE) inhibition (cilazapril, 5 mg p.o. once daily for 4 weeks) were studied at rest and during active standing by means of spectral analysis. Sympathetic vascular control was inferred from the power of the low-frequency (LF) component of the systolic arterial pressure (SAP) variability, assessed noninvasively with a plethysmographic technique. Simultaneously, quantitative indices of neural control of the sinoatrial (SA) node were obtained with the power of the LF and of the high-frequency (respiration linked) component of R-R variability. Before treatment, active standing produced a clear increase in the LF components of R-R and SAP variabilities. At the end of the 4 weeks of cilazapril treatment, the LF component of SAP variability during standing was significantly lower than prior to treatment, while the increase in the LF component of R-R variability was left unchanged. These findings suggest an inhibitory effect of chronic ACE inhibition upon vasomotor sympathetic control, as assessed non-invasively by this technique.

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.

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.

Effects of verapamil, nifedipine, and dilazep on left ventricular relaxation in the conscious dog.

The cardiac systolic and diastolic effects of the two major calcium blockers, verapamil and nifedipine, were studied and compared with those produced by dilazep, a relatively new vasodilator with calcium blocking properties, in conscious instrumented dogs to avoid the complications of anaesthesia and recent surgery. Mean arterial pressure was reduced by nifedipine and dilazep but not by verapamil, whereas peak left ventricular pressure was reduced only by dilazep and verapamil. Consistent tachycardia occurred, the rate being highest with nifedipine and lowest with dilazep. Left ventricular dP/dt was unaffected by dilazep, reduced by verapamil, and increased by nifedipine; this increase was no longer observed after beta adrenergic blockade. Ventricular relaxation was assessed by calculating the time relaxation constant, tau. Verapamil increased tau significantly only after beta adrenergic blockade, whereas nifedipine and dilazep reduced it both before and after beta adrenergic blockade. These data suggest that reflex beta adrenergic mechanisms may modulate the effects of calcium blockade on both systolic and diastolic performance.

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 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-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 approximately 0.25 Hz and a low frequency at approximately 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%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-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 beta-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.(ABSTRACT TRUNCATED AT 400 WORDS)

Continuous recording of direct high fidelity arterial pressure and electrocardiogram in ambulant patients.

A system providing high quality direct arterial blood pressure recordings and electrocardiograms in ambulatory patients was devised using a modified commercially available Holter type magnetic tape recorder together with a microminiature Millar (3F) tip transducer. This system did not require a perfusion line and solved the major drawbacks of other available systems. Pressure and electrocardiographic data were fed directly from the playback unit into a minicomputer for automatic beat to beat waveform analysis. Thus the blood pressure and RR interval variability signals could be simultaneously analysed with autoregressive modelling techniques to provide a quantitative estimate of sympathovagal balance in ambulant patients. The system was reliable, simple, and safe to use.

Simultaneous analysis of beat by beat systemic arterial pressure and heart rate variabilities in ambulatory patients.

The analysis of power spectral density (PSD) or RR variability in the electrocardiogram (ECG) has suggested that, in the early phase of essential hypertension, sympatho-vagal interaction is characterized by a sympathetic predominance. Recently, we have developed a high fidelity, direct arterial pressure ambulatory recording system which allows a beat by beat computer analysis of arterial pressure and heart rate. A microminiature tip transducer (Millar, diameter 0.8 mm) is inserted percutaneously into the radial artery and connected to a Holter two-channel magnetic tape recorder. The tip transducer has a wide band pass (> 1 kHz), excellent stability (congruent to 2 mmHg/24 h) and does not require a perfusion line. The overall frequency response of the entire recording-reproducing system is better than 20 Hz (-3 dB). The ECG and pressure signals are analysed with automatic autoregressive modelling algorithms to provide a quantitative estimate of blood pressure and heart rate variability through the computation of the PSD. In seven hypertensive patients, systolic arterial pressure and variance were higher during the day (157 +/- 9 mmHg and 122 +/- 9 mmHg2) than during the night (122 +/- 4 mmHg and 30 +/- 3 mmHg2). The PSD of RR and of systolic arterial pressure consisted of a predominant low frequency peak (congruent to 0.09 cycles/beat) during the day, and two peaks at low and high (congruent to 0.25 cycles/beat) frequency during the night. While RR variance was similar during both day- and night-time, a predominant low frequency peak was observed during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of the pressor sympathetic reflex produced by intracoronary injections of bradykinin in conscious dogs.

The reflex hemodynamic effects of intracoronary bradykinin were tested in 20 conscious instrumented dogs. When the experiments were performed after full recovery from surgery and anesthesia, graded doses (10-300 ng/kg) of bradykinin always produced graded pressor responses, in the absence of any pain reaction. At the maximum pressor response obtained with 100 ng/kg, mean arterial pressure rose 28 +/- 3% from 89 +/- 4 mm Hg, left ventricular pressure 20 +/- 3% from 121 +/- 2 mm Hg, heart rate 30 +/- 4% from 88 +/- 5 beats/min, rate of change of left ventricular pressure 18 +/- 3% from 2812 +/- 65 mm Hg/sec (P less than 0.01). Higher doses of bradykinin did not produce greater responses. The magnitude of the response was similar when the injection was performed in either the left anterior descending (change in mean arterial pressure 29 +/- 3%) or circumflex (change in mean arterial pressure 27 +/- 2%) coronary artery. The reflex nature of the response was proved by its disappearance after appropriate pharmacological blockades; moreover, after vagotomy, the pressor rise was maintained, the heart rate response was reduced (change in heart rate 10 +/- 2%), and the inotropic response was enhanced (rate of change of left ventricular pressure 24 +/- 3%). This suggested that the afferent pathway of the pressor reflex was in the sympathetic nerves and that a subordinate vagal depressor reflex was also operative. No pain reaction was obtained even when injecting very large amounts (1000-2000 ng/kg) of bradykinin, which, instead, induced arterial hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

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.