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Biomedical subjects

A Malliani

Publications and source records attributed to A Malliani.

At least 37 records · Page 2Linked to original sources

Information domain analysis of cardiovascular variability signals: evaluation of regularity, synchronisation and co-ordination.

A unifying general approach to measure regularity, synchronisation and co-ordination is proposed. This approach is based on conditional entropy and is specifically designed to deal with a small amount of data (a few hundred samples). Quantitative and reliable indexes of regularity, synchronisation and co-ordination (ranging from 0 to 1) are derived in a domain (i.e. the information domain) different from time and frequency domains. The method is applied to evaluate regularity, synchronisation and co-ordination among cardiovascular beat-to-beat variability signals during sympathetic activation induced by head-up tilt (T), during the perturbing action produced by controlled respiration at 10, 15 and 20 breaths/min (CR10, CR15 and CR20), and after peripheral muscarinic blockade provoked by the administration of low and high doses of atropine (LD and HD). It is found that: (1) regularity of the RR interval series is around 0.209; (2) this increases during T, CR10 and HD; (3) the systolic arterial pressure (SAP) series is more regular (0.406) and its regularity is not affected by the specified experimental conditions; (4) the muscle sympathetic (MS) series is a complex signal (0.093) and its regularity is not influenced by HD and LD; (5) the RR interval and SAP series are significantly, though weakly, synchronised (0.093) and their coupling increases during T, CR10 and CR15; (6) the RR interval and respiration are coupled (0.152) and their coupling increases during CR10; (7) SAP and respiration are significantly synchronised (0.108) and synchronisation increases during CR10; (8) MS and respiration are uncoupled and become coupled (0.119) after HD; (9) the RR interval, SAP and respiration are significantly co-ordinated (0.118) and co-ordination increases during CR10 and CR15; (10) during HD the co-ordination among SAP, MS and the respiratory signal is larger than that among the RR interval, SAP, MS and the respiratory signal, thus indicating that the RR interval contributes towards reducing co-ordination.

Atropine↗

Absence of sympathetic overactivity in Afro-Caribbean hypertensive subjects studied by heart rate variability.

Black hypertensives present a greater prevalence of left ventricular hypertrophy and an increased mortality compared to white hypertensives. Differences in sympathetic activity might contribute to explain these racial differences in hypertension. Nevertheless, previous laboratory studies did not show any increase of sympathetic activity direct to the heart in black subjects. The aim of the present study was to investigate the cardiac sympatho-vagal balance in black and white hypertensives analysing heart rate variability, during the entire 24 h. We analysed Holter recordings of 52 essential hypertensive patients, who had never received antihypertensive treatment, 26 of whom were black and 26 were white. Consecutive series of 300 beats, with 150 beats overlapped (approximately 600 series/day), were considered for the analysis in time and frequency domain. The mean 24-h value of the power of the low frequency spectral component (0.04-0.15 Hz), expressed in normalised units, ie a marker of sympathetic modulation, was significantly lower in the group of black patients compared to whites (respectively 40.0 +/- 2.1 vs 53.6 +/- 3.6 nu, P < 0.01). Similar results were observed for the LF/HF ratio, an index of the sympatho-vagal balance (respectively 4.11 +/- 0.58 vs 5.98 +/- 0.79; P < 0.05). In a multiple linear regression analysis, considering diastolic blood pressure, left ventricular mass index, race and age as independent variables, only race (P < 0.002) and age (P < 0.01) could independently predict the normalised low frequency power or the LF/HF ratio, as dependent variables. The results of this study suggest some blunting of the cardiac sympathetic neural modulation in black hypertensives compared to white hypertensives, during the entire 24 h.

Adult↗

Evaluation of respiratory influences on left ventricular function parameters extracted from echocardiographic acoustic quantification.

This study was designed to assess, using the echocardiographic acoustic quantification technique, the influence of respiration on left ventricular (LV) function and its modifications connected with the ageing process, quantifying in a non-invasive way the respiratory contribution to the LV volume variability. An automated algorithm is applied to extract the beat-to-beat measurements of LV function parameters from the LV volume signal, obtained from recordings lasting a few minutes. Mean values, amount of variability and spectral content were studied in a population of 17 normal young (mean age 25 +/- 1 years) and 12 normal old (mean age 64 +/- 2 years) subjects. Mean values of the beat-to-beat measurements of LV function parameters were able to point out alterations connected with the ageing process in peak filling rate, peak atrial filling rate and peak ejection rate. Spectral analysis, applied to the extracted variability series, displayed a predominance of the high-frequency (HF) component corresponding to respiration in all LV function parameters; moreover, age related changes of HF variability were observed in peak ejection rate. The HF power spectrum component of beat to beat series extracted from the LV signal can provide a non-invasive assessment of the fluctuations in ventricular parameters associated with respiration.

Adult↗

Interpreting oscillations of muscle sympathetic nerve activity and heart rate variability.

Computer analysis of spontaneous cardiovascular beat-by-beat variability has gained wide credibility as a means of inferring disturbances of autonomic cardiovascular regulation in a variety of cardiovascular conditions, including hypertension, myocardial infarction and heart failure. Recent applications of spectral analysis to muscle sympathetic nerve activity (MSNA) offer a new approach to a better understanding of the relationship between cardiovascular oscillations and autonomic regulation. However, areas of uncertainty and unresolved debates remain, mostly concerning different methodologies and interpretative models that we will consider in this article. Perusal of all available literature suggests that average sympathetic nerve activity and its oscillatory components, although correlated to some extent, are likely to provide different types of information. In addition, the specific experimental context is of paramount importance, as the rules that seem to govern the relationship between average and oscillatory properties of MSNA appear to be different in usual conditions and in conditions of extremes of activation or disease. In general, dynamic experiments, such as with graded tilt or with vasoactive drugs, are more suited to investigations of the complexity of autonomic regulation than are static comparisons. In addition, because the information is spread across variables and is affected by a potentially large error, it appears that several different techniques should be perceived as complementary rather than as mutually exclusive. Available evidence suggests that low-frequency and high-frequency oscillations in peripheral signals of variability might have a predominantly central, rather than a peripheral, origin and that this applies in particular to low-frequency oscillations. A crucial point in the assessment of the meaning of spectral components relates to consideration of the varying level of very-low-frequency noise, and the mathematical manipulation of derived indices, particularly using a normalization procedure. This appears easier to obtain with auto-regressive than with fast Fourier techniques. With this approach, discrepant interpretations seem to be resolved, provided adequate care is taken in separating direct physiological data from derived meaning, which relates to hidden information and neural codes; in the case of sympathetic discharge, the latter display greater complexity than simple average spike activity per unit time. Accordingly we believe, in conclusion, that the judicious use of spectral methodology, in addition to other techniques, might provide unprecedented, useful insights into autonomic cardiovascular regulation, in both physiopathological and clinical circumstances.

Animals↗

Prediction of short cardiovascular variability signals based on conditional distribution.

A new approach measuring the predictability of a process is proposed. The predictor is defined as the median of the distribution conditioned by a sequence of L - 1 previous samples (i.e., a pattern). A function referred to as the corrected mean squared predictor error is defined to prevent the perfect adequacy to the data (i.e., the decrease to zero of the prediction error), thus avoiding to divide the whole set of data in learning and test sets. This function exhibits a minimum and this minimum is taken as a measure of predictability of the series. The use of the minimization procedure avoids to fix a priori the pattern length L. This approach permits one a reliable measure of predictability on short data sequences (around 300 samples). Moreover, this method, in connection with a surrogate data approach, is useful to detect nonlinear dynamics. The analysis indicates that, in simulated and real data, predictability and nonlinearity measures provide different information. The application of this approach to the analysis of cardiovascular variability series of the heart period (RR interval) and systolic arterial pressure (SAP) shows: 1) SAP series is more predictable than RR interval series; 2) predictability of the RR interval series is larger during tilt, during controlled respiration at 10 breaths/min (bpm) and after high-dose administration of atropine; 3) SAP series is dominated by linear correlation; 4) RR interval series exhibits nonlinear dynamics during controlled respiration at 10 bpm and after low-dose administration of atropine, while it is linear during sympathetic activation produced by tilt and after peripheral parasympathetic blockade caused by high-dose administration of atropine.

Adult↗

Assessing baroreflex gain from spontaneous variability in conscious dogs: role of causality and respiration.

A double exogenous autoregressive (XXAR) causal parametric model was used to estimate the baroreflex gain (alpha(XXAR)) from spontaneous R-R interval and systolic arterial pressure (SAP) variabilities in conscious dogs. This model takes into account 1) effects of current and past SAP variations on the R-R interval (i.e., baroreflex-mediated influences), 2) specific perturbations affecting R-R interval independently of baroreflex circuit (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at frequencies slower than respiration), and 3) influences of respiration-related sources acting independently of baroreflex pathway (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at respiratory rate, including the effect of stimulation of low-pressure receptors). Under control conditions, alpha(XXAR) = 14.7 +/- 7.2 ms/mmHg. It decreases after nitroglycerine infusion and coronary artery occlusion, even though the decrease is significant only after nitroglycerine, and it is completely abolished by total arterial baroreceptor denervation. Moreover, alpha(XXAR) is comparable to or significantly smaller than (depending on the experimental condition) the baroreflex gains derived from sequence, power spectrum [at low frequency (LF) and high frequency (HF)], and cross-spectrum (at LF and HF) analyses and from less complex causal parametric models, thus demonstrating that simpler estimates may be biased by the contemporaneous presence of regulatory mechanisms other than baroreflex mechanisms.

Animals↗

Effects of spinal section and of positive-feedback excitatory reflex on sympathetic and heart rate variability.

The sympathetic outflow appears to be capable of displaying a rhythmicity synchronous with cardiovascular Mayer's waves even after spinal section. To test the hypothesis that spinal sympathetic low frequency (LF) oscillation can be enhanced during sympathetic excitation, we recorded cardiac sympathetic nerve activity (SNA), R-R interval, arterial pressure, and ventilation in 9 unanesthetized decerebrate-vagotomized cats before and after C1 spinal section. LF and high frequency (HF) components were detected in the variability of SNA, R-R interval, and systolic arterial pressure both before and after spinal section. In this latter condition, a significant coherence between LF(SNA) and LF(R-R) was present in 5 animals, whereas HF(SNA) and HF(R-R) were correlated in 4 animals. During an excitatory sympathetic spinal reflex elicited by aortic constriction, the efferent sympathetic firing was markedly enhanced (from 7+/-2 to 33+/-7 spikes/s); concomitantly, the powers of both LF(SNA) and HF(SNA) were also increased. Coherence between LF(SNA) and LF(R-R) became significant in all cases, whereas HF(SNA) and HF(R-R) became correlated in 6 animals. In 3 animals, the reflex sympathetic excitation was no longer elicitable after interrupting a vast contingent of sympathetic afferents by means of thoracic dorsal root section. We report for the first time that LF and HF oscillations are detectable in SNA, R-R interval, and systolic arterial pressure variabilities of decerebrate-vagotomized spinal cats and that an excitatory spinal reflex is capable of increasing the power of both SNA spectral components.

Animals↗

Conditional entropy approach for the evaluation of the coupling strength.

A method that enables measurement of the degree of coupling between two signals is presented. The method is based on the definition of an uncoupling function calculating, by means of entropy rates, the minimum amount of independent information (i.e. the information carried by one signal which cannot be derived from the other). An estimator of the uncoupling function able to deal with short segments of data (a few hundred samples) is proposed, thus enabling the method to be used for usual experimental recordings. A synchronisation index is derived from the estimate of the uncoupling function by means of a minimisation procedure. It quantifies the maximum amount of information exchanged between the two signals. Simulations in which non-linear coordination schemes are produced and changes in the coupling strength are artificially induced are used to check the ability of the proposed index to measure the degree of synchronisation between signals. The synchronisation analysis is utilised to measure the coupling strength between the beat-to-beat variability of the sympathetic discharge and ventilation in decerebrate artificially ventilated cats and the degree of synchronisation between the beat-to-beat variability of the heart period and ventricular repolarisation interval in normal subjects and myocardial infarction patients. The sympathetic discharge and ventilation are strongly coupled and the coupling strength is not affected by manoeuvres capable of increasing or depressing sympathetic activity. The synchronisation is lost after spinalisation. The synchronisation analysis confirms that the heart period and ventricular repolarisation interval are well coordinated. In normal subjects, the synchronisation index is not modified by experimental conditions inducing changes in the sympathovagal balance. On the contrary, it strongly decreases after myocardial infarction, thus detecting and measuring the uncoupling between the heart period and ventricular repolarisation interval.

Animals↗

Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans.

BACKGROUND: The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation. METHODS AND RESULTS: To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90 degrees head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, approximately 0.1-Hz) and high-frequency (HF, approximately 0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly. CONCLUSIONS: Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.

Adolescent↗

Central vagotonic effects of atropine modulate spectral oscillations of sympathetic nerve activity.

BACKGROUND: Low-dose atropine causes bradycardia either by acting on the sinoatrial node or by its effects on central muscarinic receptors increasing vagal activity. Any central muscarinic effects of high-dose atropine on RR interval are masked by peripheral muscarinic blockade at the sinoatrial node, which causes tachycardia. Effects of central parasympathetic activation on sympathetic activity are not known. METHODS AND RESULTS: Using power spectral analysis of RR interval, intra-arterial blood pressure, respiration, and muscle sympathetic nerve activity (MSNA), we examined the effects of both low (2 microgram/kg IV) and high (15 microgram/kg IV) doses of atropine. After low-dose atropine, RR increased by 9+/-1% (P<0.0001), the low-frequency (LF) component (in normalized units, NU) of RR variability decreased by -32+/-8%, and the high-frequency (HF)NU component increased (+74+/-19%); hence, LF/HF of RR variability fell by 52+/-10% (all P<0.01). Although overall MSNA did not change, LFNU of MSNA decreased (-15+/-5%), HFNU of MSNA increased (+31+/-3%), and LF/HF of MSNA fell (-41+/-8%) (all P<0.01). After high-dose atropine, LFNU of MSNA decreased (-17+/-12%), HFNU of MSNA increased (+22+/-3%), and LF/HF of MSNA fell (-51+/-21%) (all P<0.02). CONCLUSIONS: Increasing central parasympathetic activity with low-dose atropine is associated with an increase in the HF and a decrease in the LF oscillations of both RR interval and MSNA variability. High-dose atropine similarly induces an increase in the HF and a decrease in the LF components of MSNA variability. Thus, central parasympathetic activation is able to modulate the oscillatory characteristics of sympathetic nerve traffic to peripheral blood vessels.

Adult↗

Myocardial beta-adrenergic and muscarinic receptor density in cardiac pressure or volume overload.

Decreased myocardial beta-adrenergic receptor density has been demonstrated in experimental and clinical models of cardiac disease. Nevertheless, the individual role played by pressure or volume overload in determining the receptor downregulation has never been described in humans. Moreover, no data have been reported about the reversibility of the downregulation after non-pharmacological improvement of cardiac function. In the present study, we measured the myocardial beta-adrenergic and muscarinic receptor density, using an autoradiographic method, in 14 patients with cardiac pressure overload (aortic stenosis) and in five patients with cardiac volume overload (aortic regurgitation). Five patients with aortic stenosis were studied again six months after successful valve replacement. A significant lower density of beta-adrenergic receptors was observed in patients with a chronic pressure overload compared to those with a chronic volume overload (20+/-2 and 28+/-2 fmol/mg protein, respectively P<0.05). No significant differences were found between the two groups regarding beta-adrenoceptor sub-types proportion and muscarinic receptor density. Six months after successful aortic valve replacement, we observed a significant upregulation of the beta-adrenoceptor density (delta 29+/-9 fmol/mg protein P<0.05). In conclusion, these observations indicate that: (a) the type of left ventricle haemodynamic overload may be a quantitative determinant factor in the myocardial beta-adrenoceptor downregulation; (b) the reduction of a pathological cardiac load leads to an upregulation of these receptors.

Adult↗

Quantifying electrocardiogram RT-RR variability interactions.

A dynamic linear parametric model is designed to quantify the dependence of ventricular repolarisation duration variability on heart period changes and other immeasurable factors. The model analyses the beat-to-beat series of the RR duration and of the interval between R- and T-wave apexes (RT period). Directly from these two signals, a parametric identification procedure and spectral decomposition techniques allow RT variability to be divided into RR-related and RR-unrelated parts and allow the RT-RR transfer function to be calculated. RT variability is driven by RR changes at low frequency (LF, around 0.1 Hz) and high frequency (HF, at the respiratory rate), whereas, at very low frequencies, the RR-unrelated contribution to the total RT variability is remarkable. During tilt at LF the RR-related RT percentage power increases (p < 0.02), the RR-unrelated RT percentage power remains unchanged, the gain of the RT-RR relationship largely increases (p < 0.001), and the phase is not significantly modified. Both the RR-related and the RR-unrelated RT percentage powers at LF are not affected by controlled respiration, and an increase in the RT-RR gain at HF is observed (p < 0.02). The proposed analysis may help to describe the regulation of the ventricular repolarisation process and to extract indexes quantifying the coupling between heart period and ventricular repolarisation interval changes.

Electrocardiography↗

Measuring regularity by means of a corrected conditional entropy in sympathetic outflow.

A new method for measuring the regularity of a process over short data sequences is reported. This method is based on the definition of a new function (the corrected conditional entropy) and on the extraction of its minimum. This value is taken as an index in the information domain quantifying the regularity of the process. The corrected conditional entropy is designed to decrease in relation to the regularity of the process (like other estimates of the entropy rate), but it is able to increase when no robust statistic can be performed as a result of a limited amount of available samples. As a consequence of the minimisation procedure, the proposed index is obtained without an a-priori definition of the pattern length (i.e. of the embedding dimension of the reconstructed phase space). The method is validated on simulations and applied to beat-to-beat sequences of the sympathetic discharge obtained from decerebrate artificially ventilated cats. At control, regular, both quasiperiodic and periodic (locked to ventilation) dynamics are observed. During the sympathetic activation induced by inferior vena cava occlusion, the presence of phase-locked patterns and the increase in regularity of the sympathetic discharge evidence an augmented coupling between the sympathetic discharge and ventilation. The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation.

Animals↗

Improvement of left ventricular function and cardiovascular neural control after endoventriculoplasty and myocardial revascularization.

OBJECTIVE: To investigate the effects of endoventriculoplasty (EVP) and myocardial revascularization on left ventricular function and on sympathovagal balance modulating sinus node and vasomotor activity, we studied patients with left anterior, septal or anteroseptal ventricular aneurysm, before and after surgery. It has been demonstrated that, compared to the standard aneurismectomy, EVP associated with coronary grafting has a lower operative mortality and improves ventricular function, clinical status and prognosis. METHODS: We collected pre- and post-operative echocardiographic and angiographic data to determine morphological and hemodynamic changes. The pre- and post-operative neural cardiovascular control was assessed by power spectrum analysis of heart rate and systolic arterial pressure (SAP) variabilities during rest and tilt. RESULTS: As expected, post-operative ventricular function improved significantly: ejection fraction increased from 33 +/- 2 to 46 +/- 3% (p < 0.01) when assessed by echocardiography and from 40 +/- 4 to 55 +/- 5% (p < 0.01) when assessed by angiography; left ventricular end-diastolic pressure fell from 22 +/- 3 to 13 +/- 2 mmHg (p < 0.05). Pre-operatively sympathovagal balance responsiveness was blunted: tilt test did not induce, in respect to resting values, any significant change in low frequency (LFRR) and high frequency (HFRR) components of RR variability (in normalized units, n.u.) and in LFSAP. Post-operatively, tilt induced significant changes in LFRR and HFRR (in n.u.), in LF/HF ratio and LFSAP in respect to resting values. The pre- and post-operative percent differences--delta%--, from rest to tilt, of LFRR, HFRR, LF/HF and LFSAP were also significantly different (p < 0.01, p < 0.05, p < 0.05, p < 0.05). In addition, we compared data obtained from survivors and non-survivors (6 out of 19 patients died within 4 months because of heart failure). Non-survivors were characterized by significantly lower RR variance (184 +/- 80 vs. 1193 +/- 309 ms2 at rest, 196 +/- 87 vs. 546 +/- 104 ms2 during tilt, p < 0.05) and lower LFRR (15 +/- 7 vs. 61 +/- 6 at rest, 23 +/- 10 vs. 58 +/- 6 during tilt, in n.u., p < 0.01). CONCLUSIONS: (1) The improvement of ventricular function induced by EVP and myocardial revascularization is accompanied by a restored capability to oscillate of cardiovascular neural regulatory mechanisms; (2) the drastic reduction of variance and LF component from RR variability seems to be associated with an ominous outcome.

Aged↗

Autonomic effects of nicotine patch administration in habitual cigarette smokers: a double-blind, placebo-controlled study using spectral analysis of RR interval and systolic arterial pressure variabilities.

Nicotine patch administration is often used to sustain tobacco abstinence in smoking-cessation programs. There is some concern regarding safety issues, as a consequence of the sympathomimetic action of nicotine. We used spectral analysis of RR interval and (noninvasive) systolic arterial pressure (SAP) beat-by-beat variabilities in a crossover double-blind design to assess the autonomic effects of cigarette smoking, of transdermal nicotine, and of placebo. The study group consisted of 27 heavy smokers (age 43 +/- 2 years). The RR interval and its variability were significantly reduced in the smoking group, as compared with nicotine or placebo groups. The LF component of RR interval variability (in normalized units, nu), and the LF/HF ratio showed greatest values during smoking, as compared with placebo. Values of LF(RR) and LF/HF during nicotine patch treatment were slightly, but not significantly, greater than observed with placebo. No differences were observed in SAP and its variability components. The index alpha (a frequency domain measure of baroreflex gain) was minimal in the smoking period. Habitual cigarette smoking is associated with signs of sympathetic predominance in the autonomic control of the sinoatrial (SA) node. Nicotine patches produce only minor disturbances of autonomic regulation. This corroborates their safe use in smoking-cessation strategies.

Administration, Cutaneous↗