Methodological aspects of noninvasive analysis of autonomic regulation of cardiovascular variability.
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Autonomic Nervous System↗
Biomedical subjects
A Malliani
Publications and source records attributed to A Malliani.
Spectral analysis of short term R-Tapex interval variability during sinus rhythm and fixed atrial rate.
Analysis of heart rate variability has been proven useful in stratifying post myocardial patients at risk and in evaluating autonomic dysfunction. Recently augmented inter-lead variability of the QT interval has been associated with increased mortality as a result of arrhythmia and proposed as a marker of dispersion of ventricular repolarization. As the duration of the QT interval is largely dependent upon the length of the preceding cardiac cycle it is tempting to analyse whether neural mechanisms might also directly exert additional modulation. Using autoregressive algorithms we therefore analysed RR and R-Tapex interval variabilities in 15 normal subjects during sinus rhythm and in six patients with a fixed atrial rate. In controls mean R-Tapex interval and variance measured on the vector magnitude were, respectively, 245 +/- 6 ms and 5.1 +/- 0.7 ms2. Spectral analysis of R-Tapex indicated the presence of two spectral components which corresponded to the low and high frequency components of heart rate variability. In R-Tapex variability, high frequency (44 +/- 4 nu) was predominant over low frequency (29 +/- 4 nu). During controlled respiration, a manoeuvre associated with enhanced vagal modulation of sinus node, there was a further increase in high frequency (58 +/- 4 nu) whereas during tilt the low frequency component of R-Tapex variability became predominant (57 +/- 6 nu). In patients with a fixed atrial rate, variance was extremely low (3 +/- 0.9 ms2) and only a respiration-related high frequency component was recognizable in spectral analysis of RR and R-Tapex variabilities. This component was likely to depend upon mechanically induced changes in cardiac vector orientation. These data indicate that during sinus rhythm short-term R-Tapex interval variability is characterized by the same rhythmical components present in RR variability. However, the presence of a very low variance and of only a high frequency component in patients in whom the physiological variability of sinus node is abolished by atrial pacing. suggests that neural modulatory mechanisms do not exert a direct effect on the length of the R-Tapex interval.
Adult↗
Non-linear dynamics and chaotic indices in heart rate variability of normal subjects and heart-transplanted patients.
OBJECTIVES: Heart rate variability (HRV) is characterised by a variety of linear, non-linear, periodical and non-periodical oscillations. The aim of the present study was mainly to investigate the role played by neural mechanisms in determining non-linear and non-periodical components. METHODS: Analysis was performed in 7 recently heart transplanted patients and in 7 controls of similar age whose HRV signal was collected during 24 h. Parameters that quantify non-linear dynamic behaviour, in a time series, were calculated. We first assessed the specific non-linear nature of the time series by a test on surrogate data after Fourier phase randomization. Furthermore, the D2 correlation dimension, K2 Kolmogorov entropy, and H self-similarity exponent of the signal were estimated. From this last parameter, the dimension D = 1/H can be obtained. In order to assess whether the dynamics of the system are compatible with chaotic characteristics, the entire spectrum of Lyapunov exponents was calculated. We used return maps to graphically represent the non-linear and non-periodical behaviours in patients and controls. RESULTS: Surrogate data suggest that the HRV time courses have unique non-linear characteristics. D2, K2 and 1/H parameters were significantly lower in transplanted subjects than in controls. Positivity of the first Lyapunov exponent indicates divergence of trajectories in state-space. Furthermore, the display of return maps on projections obtained after Singular Value Decomposition, especially in low-complexity data (as in transplanted patients), shows a structure which is suggestive of a strange attractor. These findings support the hypothesis that chaotic dynamics underlie HRV. CONCLUSION: These results indicate that non-linear dynamics are likely to be present in HRV control mechanisms, giving rise to complex and qualitatively different behaviours. System complexity decreases in transplanted patients and this may be related to loss of the neural modulation of heart rate.
Adult↗
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.
Adult↗
[Nervous mechanisms and ischemic cardiopathy].
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Animals↗
Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion.
Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.
Adenosine↗
Pure Autonomic Failure: complex abnormalities in the neural mechanisms regulating the cardiovascular system.
The aim of this study was to evaluate the sympatho-vagal interaction modulating cardiovascular function and the possible impairment of baroreceptor sensitivity in patients affected by Pure Autonomic Failure (PAF). We studied 4 patients affected by PAF and 7 controls at rest and during different levels (45 degrees, 60 degrees, 90 degrees) of head-up tilt. On a different day all subjects underwent i.v. administration of phenylephrine at dosages adequate to enhance systolic blood pressure by about 20 mmHg both at rest and during 45 degrees head-up tilt. Finally, 1.5 mg atropine was infused intravenously only in the patients. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided markers of sympathetic (low-frequency oscillations, about 0.1 Hz, LFRR) and vagal (high-frequency oscillations, about 0.25 Hz, HFRR) modulations of heart period and of sympathetic vasomotor activity (low-frequency oscillations of SAP variability, LFSAP). Baroreceptor mechanisms were quantified by means of the index alpha (calculated from the square root of the ratio between the powers of HF components of RR interval and SAP variabilities) and of the phenylephrine RR-SAP slope. Patients affected by PAF were characterized by a drastic decrease in total power of RR variability and by the absence of LFRR and LFSAP components. Moreover, HFRR, although largely predominant in its relative value, was also markedly reduced in its absolute value. Finally, the baroreceptive mechanisms appeared to be heavily impaired. In conclusion, PAF patients seem to be characterized by a complex alteration of neural mechanisms, which in addition to the signs of a sympathetic denervation include an impairment, at least functional, of the vagal modulation of heart rate.
Atropine↗
Power spectral analysis of heart rate variability and baroreflex gain.
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Animals↗
Sympathetic predominance followed by functional denervation in the progression of chronic heart failure.
Using spectral analysis of heart rate and systolic arterial pressure variabilities, the study was set up to evaluate cardiovascular efferent autonomic modulation in patients with different degrees of chronic heart failure. We studied 30 patients with stable chronic heart failure and 15 controls of similar age. ECG, arterial blood pressure and respiratory signal were recorded at rest, during controlled respiration and during passive head-up tilting. R-R interval periods of 256-512 were analysed. Routine 2D echocardiogram and Doppler studies were also carried out. As expected, we found a decrease in the mean and variance of R-R intervals in patients with sever heart failure. In New York Heart Association (NYHA) class II patients, the power spectral pattern of R-R variability was characterized by the predominance of the low frequency component (72 +/- 3 nu), considered a marker of sympathetic activity, and by its unresponsiveness to tilting. Patients in NYHA class III also presented blunted changes in spectral components during tilting. A drastic decrease in the variance of R-R intervals (191 +/- 58 vs 1056 +/- 149 ms2 in controls) and an almost complete absence of the low frequency spectral component (8 +/- 3 nu) were present in patients in NYHA class IV. Controlled respiration, which in normal subjects decreased the low frequency component, induced changes that blunted progressively as heart failure increased. These data suggest that autonomic neural modulation and cardiovascular response to neural activity differ at different stages of the disease.
Analysis of Variance↗
[Role of low-frequency neuronal activity in the medulla in the regulation of the cardiovascular system].
We recorded discharge activity of 45 single neurons located in the rostral ventrolateral medulla (n = 21), lateral tegmental field (n = 10) and caudal raphe (n = 14) nuclei in baroreceptor-denervated decerebrate cats (n = 27). Autoregressive spectral analysis was performed on neuronal activity and systolic arterial pressure (SAP). The discharges of the recorded neurons were correlated to 2- to 6 Hz oscillations or 10 Hz rhythm present in sympathetic neural discharge. A low frequency (LF) oscillation (0.12 +/- 0.02 Hz) was observed in 25 (55%) units. The same rhythmicity was found in SAP variability in 25 of 45 (55%) recordings. In 21 of these cases the LF in SAP variability was highly correlated to LF in neural activity. Moreover, 32 out of 45 (71%) neurons showed a higher rhythm (HF; 0.34 +/- 0.06 Hz) related to the ventilation rate. These data demonstrate the presence of an LF oscillation in the discharge of single medullary neurons, involved in the regulation of cardiovascular system. This LF component was similar to that detectable in the spectral analysis of SAP variability, thus supporting the hypothesis of a central origin of this rhythm, largely independent of baroreceptor input.
Analysis of Variance↗
Mechanical effects of respiration and stepping on systolic arterial pressure variability during treadmill exercise.
AIM: To evaluate the changes produced by maximal dynamic exercise in the rhythmic components of systolic arterial pressure variability. PATIENTS AND METHODS: We studied seven normotensive subjects during different levels of a modified treadmill test (Bruce protocol, up to stage 4). Arterial pressure was measured directly by a high-fidelity microtip pressure transducer. Spectral analysis provided two main oscillatory components of systolic arterial pressure variability, a low-frequency component related to the sympathetic-mediated neural control of vasomotion and a high-frequency component reflecting the mechanical effects of respiration on blood pressure. RESULTS: The low-frequency component increased at the beginning of exercise and remained stable thereafter, while the high-frequency component increased progressively. A third rhythmic component (very high frequency) with a frequency higher than respiration and synchronous with the rate of the subjects' footsteps, which was undetectable on a visual inspection of analog tracings, became progressively more apparent, reaching its maximum at exercise stage 4. CONCLUSIONS: These findings emphasize the importance of high-fidelity techniques and computer analysis for the evaluation of arterial pressure variability in dynamic conditions.
Adult↗
Analysis of initial autonomic adjustments to moderate exercise in humans.
OBJECTIVE: To determine whether signs of cardiac sympathetic activation (together with vagal withdrawal) can be observed in the autonomic balance modulating the sino-atrial node as early as the initial levels of a graded light dynamic exercise. PATIENTS AND METHODS: We studied 15 healthy ambulant subjects (mean +/- SD age 32 +/- 9 years; systolic/diastolic blood pressure 120 +/- 19/77 +/- 7 mmHg; heart rate 65 +/- 9 beats/min), who underwent a control recording of 10 min, followed by a three-step progressive (10, 20 and 30% of nominal maximum for age and sex) supine bicycle exercise. Spectral and cross-spectral analysis of RR and systolic arterial pressure variabilities were used to obtain non-invasive markers of the autonomic adjustments to exercise. RESULTS: The low-frequency component of RR interval variability (which, in normalized units, is a marker of sympathetic modulation of the sino-atrial (SA) node) was progressively increased during all three stages of bicycle exercise. No significant changes were observed in the low-frequency component of systolic arterial pressure variability (i.e. a marker of sympathetic drive to the vasculature) in the early stages of exercise, while a significant increase was observed at 30% of maximum. The index alpha (which provides a measure of the gain of the arterial pressure-heart period baroreflex) was progressively reduced during all three stages of exercise. CONCLUSIONS: While the sympathovagal balance modulating the SA node is immediately shifted towards sympathetic predominance (and vagal withdrawal), markers of peripheral vascular sympathetic activation appear increased only when 30% of maximum exercise is attained.
Adult↗
Effects of beta blockers (atenolol or metoprolol) on heart rate variability after acute myocardial infarction.
This study analyzed, with spectral techniques, the effects of atenolol or metoprolol on RR interval variability in 20 patients 4 weeks after the first uncomplicated myocardial infarction. Beta blocker-induced bradycardia was associated with a significant increase in the average 24-hour values of RR variance (from 13,886 +/- 1,479 to 16,728 +/- 1,891 ms2) and of the normalized power of the high-frequency component (from 22 +/- 1 to 28 +/- 2 normalized units), whereas the low-frequency component was greatly reduced (from 60 +/- 3 to 50 +/- 3 normalized units). When considering day and nighttime separately, the effects of both drugs were more pronounced in the daytime. In addition, a marked attenuation was observed in the circadian variation of the low-frequency component after beta blockade. As a result, the early morning increase of the spectral index of sympathetic modulation was no longer detectable. These results indicate that beta-blocker administration has important effects on RR interval variability and on its spectral components. The observed reduction in signs of sympathetic activation and the increase in vagal tone after beta blockade help to explain the beneficial effects of these drugs after myocardial infarction. However, the potential clinical relevance of the increase in RR variance remains to be established.
Atenolol↗
Physiology and clinical implications of variability of cardiovascular parameters with focus on heart rate and blood pressure.
Power spectral analysis of heart period (R-R) and arterial pressure short-term variability reveals the existence of two rhythmic oscillations: a high frequency (HF) component corresponding to respiratory activity (around 0.25 Hz) and a low frequency (LF) component corresponding to vasomotor waves (around 0.10 Hz). Further, a very low frequency (VLF) component, with a center frequency around 0 Hz, can be identified. It is generally accepted that the power of the HF component of R-R variability is a marker of vagal activity to the sinoatrial node. We have introduced the hypothesis, which is becoming progressively accepted, that the LF component of R-R variability is a marker of sympathetic modulation of the sinoatrial node, whereas the LF component of arterial pressure variability is a marker of sympathetic modulation of vasomotor tone. Moreover, we have suggested that the evaluation (in normalized units) of the LF and HF components of R-R variability (or the LF/HF ratio) can assess the state of the sympatho-vagal balance modulating the sino-atrial node in numerous physiologic and physiopathologic conditions. A large body of evidence has been gathered on the basis of multiple recordings of cardiovascular signals obtained in humans and in acute and chronic animal experiments in favor of this hypothesis.
Blood Pressure↗
Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences.
A model which assesses the closed-loop interaction between heart period (HP) and arterial pressure (AP) variabilities and the influence of respiration on both is applied to evaluate the sources of low frequency (LF approximately 0.1 Hz) and high frequency (HF, respiratory rate approximately 0.25 Hz) in conscious dogs (n = 18) and humans (n = 5). A resonance of AP closed-loop regulation is found to amplify LF oscillations. In dogs, the resonance gain increases slightly during baroreceptor unloading (mild hypotension obtained with nitroglycerine (NTG) i.v. infusion, n = 8) and coronary artery occlusion ((CAO), n = 6), and it is abolished by ganglionic transmission blockade ((ARF), Arfonad i.v. infusion, n = 3). In humans, this gain is considerably increased by passive tilt. Different, possibly central, sources of LF oscillations are also evaluated, finding a strong rhythmic modulation of HP during CAO. At HF, a direct respiratory arrhythmia is dominant in dogs at control, while it is considerably reduced during CAO. On the contrary, in humans, a strong influence of respiration on AP is shown which induces a reflex respiratory arrhythmia. An index of the gain of baroreceptive response, alpha cl, was decreased by NTG and CAO, and virtually abolished by chronic arterial baroreceptive denervation (TABD, n = 4) and ARF.
Animals↗
Altered dynamics of the circadian relationship between systemic arterial pressure and cardiac sympathetic drive early on in mild hypertension.
1. This study was designed to test the hypothesis that simultaneous non-invasive assessment of the circadian variations in both intermittent arterial pressure and the continuous 24 h changes of spectral markers of cardiac neural control could provide new information on cardiovascular regulatory mechanisms, in hypertensive patients and normotensive subjects. To test this hypothesis we studied 18 subjects with mild hypertension and 11 normotensive subjects in whom we recorded simultaneously non-invasive intermittent arterial pressure and Holter electrocardiogram for 24 h. We also studied the same subjects during resting and standing conditions in the clinical laboratory. 2. The normalized power of the low-frequency (approximately 0.1 Hz) spectral component of R-R interval variability, considered mainly a marker of sympathetic drive to the sino-atrial node, was, at rest, significantly higher in the hypertensive than in the normotensive subjects, as already reported. Moreover, the values of the low-frequency component at rest recorded in the clinical laboratory were significantly correlated with those obtained from ambulatory recording during night rest. The decrease in the values of arterial pressure during the night-time was accompanied by a reduction in the power of the low-frequency component only in the case of normotensive subjects. Accordingly, the slope of the regression of the low-frequency component as a function of systolic arterial pressure during ambulatory recordings was steep in normotensive subjects and flat in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Sympathetic restraint of baroreflex control of heart period in normotensive and hypertensive subjects.
1. We assessed the effects of changing levels of sympathetic drive on the gain of baroreflex control of the sino-atrial node, in normotensive and hypertensive subjects. 2. Autoregressive spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (non-invasive Finapres method) variabilities providing an estimate of baroreflex gain through the frequency domain index alpha were performed on data from 63 normotensive and 78 mild hypertensive subjects. Subjects were studied at rest and during active orthostatism, which induces sympathetic predominance. Seven control subjects and 14 hypertensive subjects were also studied after chronic atenolol treatment, to attenuate beta-adrenoceptor-mediated responses. 3. In both normotensive and hypertensive subjects, the index alpha was reduced by active standing and increased by chronic beta-adrenoceptor blockade. Furthermore, at rest, the index alpha was correlated with R-R variance and appeared significantly reduced with age. The age-related negative correlation of the index alpha was no longer evident during the standing-induced increase in sympathetic drive, in both normotensive and hypertensive subjects. 4. The index alpha, a non-invasive frequency domain estimate of the overall gain of baroreflex control of the sino-atrial node, which appears to be reduced in essential hypertension, is negatively modulated by physiological increases in sympathetic drive, and augmented by pharmacological blockade of beta-adrenoceptors. 5. In essential hypertension the enhanced sympathetic drive present already at rest, and the simultaneous reduction of the gain of baroreflex mechanisms, are the expression of a complex alteration in neural cardiovascular control.
Adult↗
Sympathetic overactivity in subjects complaining of unexplained fatigue.
1. Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate. 2. Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively. 3. We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest. 4. The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.
Autonomic Nervous System↗