Preoperative autonomic nervous system analysis may stratify the risk of hypotension after spinal anesthesia.

BACKGROUND: Studies on pregnant women undergoing cesarean delivery or elderly men scheduled for prostate brachytherapy have demonstrated the predictive value of heart rate variability (HRV) analysis for hypotension during spinal anesthesia. We conducted a prospective observational study to investigate if preoperative HRV analysis may have a role in identifying the risk of hypotension following spinal anesthesia in otherwise healthy patients. METHODS: The study investigated 47 ASA physical status I-II patients aged between 18-50 years that underwent subarachnoid anesthesia for lower abdominal or orthopedic scheduled surgery. ECG was recorded from all subjects before the subarachnoid block. We analysed the autonomic nervous system modulation, measured by HRV analysis. The variables that were be considered were preoperative HRV total power, low frequency (LF) and high frequency (HF) heart beat oscillations and LF/HF ratio. The LF/HF ratio was dichotomized according to the median for sensitivity analysis. The lowest arterial pressure value between spinal anesthesia and the end of surgery was recorded. RESULTS: The median LF/HF before anesthesia was 2.3. We considered two groups of 23 (LF/HF<2.3, group LOW) and 24 (LF/HF>2.3, group HIGH) patients respectively. Both groups had similar baseline demographic and hemodynamic variables. A high preoperative sympathetic outflow and loss of vagal modulation, as stated by LF/HF>2.3, was correlated with a relative risk of 7.7 (95%CI 1.04 to 56.6, p=0.023) of post-spinal hypotension. CONCLUSIONS: Preoperative analysis of autonomic nervous system modulation might be useful to stratify the risk of post-spinal hypotension and it might indicate the need for careful monitoring or prophylactic fluids.

Surgical Pleth Index guided analgesia blunts the intraoperative sympathetic response to laparoscopic cholecystectomy.

BACKGROUND: Surgical noxious stimuli generate a stress response with an increased sympathetic activity, potentially affecting the perioperative outcome. Surgical Pleth Index (SPI), derived from the pulse plethysmogram, has been proposed as a tool to assess nociception-antinociception balance. The relationship between SPI and autonomic nervous system (ANS) during general anesthesia is poorly understood and it is doubtful if SPI-guided analgesia may offer advantages over the standard clinical practice. The study was designed to evaluate if SPI-guided analgesia leads to a lower sympathetic modulation compared with standard clinical practice. METHODS: Electrocardiographic wave, non-invasive blood pressure and SPI were recorded in ASA I-II patients undergoing elective laparoscopic cholecystectomy, randomized to receive SPI-guided analgesia or standard analgesia. Hemodynamic parameters, SPI, mean and variance of heart rate, low (LF) and high frequency (HF) spectral components of heart rate variability were measured at four time points: (T0) baseline, (T1) after induction of general anesthesia, (T2) after pneumoperitoneum insufflation and (T3) after pneumoperitoneum withdrawal. RESULTS: SPI, hemodynamic and ANS parameters changed significantly in both groups during the study period (P<0.0001). At T2 SPI and markers of sympathetic modulation were significantly lower in SPI group (mean [SD] SPI 38.1 [15.3] vs. 48.1 [16.2] normalized units, P<0.05; LF 38 [8.6] vs. 56.2 [20.6] normalized units, P<0.01; LF/HF 1.01 [1.1] vs. 2.68 [2.07], P<0.01). There was no difference in remifentanil consumption, recovery time from anesthesia, or postoperative pain and complications. CONCLUSION: SPI-guided analgesia led to a more stable sympathetic modulation but didn't seem to offer clinically relevant advantages over the standard clinical practice for laparoscopic cholecystectomy.

Influence of gravitational sympathetic stimulation on the Surgical Plethysmographic Index.

Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels.

Autonomic cardiovascular modulation with three different anesthetic strategies during neurosurgical procedures.

BACKGROUND: Autonomic cardiovascular modulation during surgery might be affected by different anesthetic strategies. Aim of the present study was to assess autonomic control during three different anesthetic strategies in the course of neurosurgical procedures by the linear and non-linear analysis of two cardiovascular signals. METHODS: Heart rate (EKG-RR intervals) and systolic arterial pressure (SAP) signals were analyzed in 93 patients during elective neurosurgical procedures at fixed points: anesthetic induction, dura mater opening, first and second hour of surgery, dura mater and skin closure. Patients were randomly assigned to three anesthetic strategies: sevoflurane+fentanyl (S-F), sevoflurane+remifentanil (S-R) and propofol+remifentanil (P-R). RESULTS: All the three anesthetic strategies were characterized by a reduction of RR and SAP variability. A more active autonomic sympathetic modulation, as ratio of low to high frequency spectral components of RR variability (LF/HF), was present in the P-R group vs. S-R group. This is confirmed by non-linear symbolic analysis of RR series and SAP variability analysis. In addition, an increased parasympathetic modulation was suggested by symbolic analysis of RR series during the second hour of surgery in S-F group. CONCLUSION: Despite an important reduction of cardiovascular signal variability, the analysis of RR and SAP signals were capable to detect information about autonomic control during anesthesia. Symbolic analysis (non-linear) seems to be able to highlight the differences of both the sympathetic (slow) and vagal (fast) modulation among anesthetics, while spectral analysis (linear) underlines the same differences but only in terms of balance between the two neural control systems.

Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity.

We used the microdialysis technique to compare basal extracellular serotonin (5-HT) and the response to citalopram in different strains of mice with functionally different allelic forms of tryptophan hydroxylase-2 (TPH-2), the rate-limiting enzyme in brain 5-HT synthesis. DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele of TPH-2 had less dialysate 5-HT in the medial prefrontal cortex and dorsal hippocampus (DH) (20-40% reduction) than C57BL/6J and C57BL/6N mice carrying the 1473C allele. Extracellular 5-HT estimated by the zero-net flux method confirmed the result of conventional microdialysis. Citalopram, 1.25, 5 and 20 mg/kg, dose-dependently raised extracellular 5-HT in the medial prefrontal cortex of C57BL/6J mice, with maximum effect at 5 mg/kg, but had significantly less effect in DBA/2J and BALB/c mice and in the DH of DBA/2J mice. A tryptophan (TRP) load enhanced basal extracellular 5-HT in the medial prefrontal cortex of DBA/2J mice but did not affect citalopram's ability to raise cortical and hippocampal extracellular 5-HT. The impairment of 5-HT synthesis quite likely accounts for the reduction of basal 5-HT and the citalopram-induced rise in mice carrying the mutated enzyme. These findings might explain why DBA/2 and BALB/c mice do not respond to citalopram in the forced swimming test. Although TRP could be a useful strategy to improve the antidepressant effect of citalopram (Cervo et al. 2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated.

An integrated approach based on uniform quantization for the evaluation of complexity of short-term heart period variability: Application to 24 h Holter recordings in healthy and heart failure humans.

We propose an integrated approach based on uniform quantization over a small number of levels for the evaluation and characterization of complexity of a process. This approach integrates information-domain analysis based on entropy rate, local nonlinear prediction, and pattern classification based on symbolic analysis. Normalized and non-normalized indexes quantifying complexity over short data sequences ( approximately 300 samples) are derived. This approach provides a rule for deciding the optimal length of the patterns that may be worth considering and some suggestions about possible strategies to group patterns into a smaller number of families. The approach is applied to 24 h Holter recordings of heart period variability derived from 12 normal (NO) subjects and 13 heart failure (HF) patients. We found that: (i) in NO subjects the normalized indexes suggest a larger complexity during the nighttime than during the daytime; (ii) this difference may be lost if non-normalized indexes are utilized; (iii) the circadian pattern in the normalized indexes is lost in HF patients; (iv) in HF patients the loss of the day-night variation in the normalized indexes is related to a tendency of complexity to increase during the daytime and to decrease during the nighttime; (v) the most likely length L of the most informative patterns ranges from 2 to 4; (vi) in NO subjects classification of patterns with L=3 indicates that stable patterns (i.e., those with no variations) are more present during the daytime, while highly variable patterns (i.e., those with two unlike variations) are more frequent during the nighttime; (vii) during the daytime in HF patients, the percentage of highly variable patterns increases with respect to NO subjects, while during the nighttime, the percentage of patterns with one or two like variations decreases.

Automatic classification of interference patterns in driven event series: application to single sympathetic neuron discharge forced by mechanical ventilation.

This study proposes a method for the automatic classification of nonlinear interactions between a strictly periodical event series modelling the activity of an exogenous oscillator working at a fixed and well-known rate and an event series modelling the activity of a self-sustained oscillator forced by the exogenous one. The method is based on a combination of several well-known tools (probability density function of the cyclic relative phase, probability density function of the count of forced events per forcing cycle, conditional entropy of the cyclic relative phase sequence and a surrogate data approach). Classification is reached via a sequence of easily applicable decision rules, thus rendering classification virtually user-independent and fully reproducible. The method classifies four types of dynamics: full uncoupling, quasiperiodicity, phase locking and aperiodicity. In the case of phase locking, the coupling ratio (i.e. n: m) and the strength of the coupling are calculated. The method, validated on simulations of simple and complex phase-locking dynamics corrupted by different levels of noise, is applied to data derived from one anesthetized and artificially ventilated rat to classify the nonlinear interactions between mechanical ventilation and: (1) the discharges of two (contemporaneously recorded) single postganglionic sympathetic neurons innervating the caudal ventral artery in the tail and (2) arterial blood pressure. Under central apnea, the activity of the underlying sympathetic oscillators is perturbed by means of five different lung inflation rates (0.58, 0.64, 0.76, 0.95, 1.99 Hz). While ventilation and arterial pressure are fully uncoupled, ventilation is capable of phase locking sympathetic discharges, thus producing 40% of phase-locked patterns (one case of 2:5, 1:1, 3:2 and 2:2) and 40% of aperiodic dynamics. In the case of phase-locked patterns, the coupling strength is low, thus demonstrating that this pattern is sliding. Non-stationary interactions are observed in 20% of cases. The two discharges behave differently, suggesting the presence of a population of sympathetic oscillators working at different frequencies.

Entropy, entropy rate, and pattern classification as tools to typify complexity in short heart period variability series.

An integrated approach to the complexity analysis of short heart period variability series (approximately 300 cardiac beats) is proposed and applied to healthy subjects during the sympathetic activation induced by head-up tilt and during the driving action produced by controlled respiration (10, 15, and 20 breaths/min, CR10, CR15, and CR20 respectively). The approach relies on: 1) the calculation of Shannon entropy (SE) of the distribution of patterns lasting three beats; 2) the calculation of a regularity index based on an entropy rate (i.e., the conditional entropy); 3) the classification of frequent deterministic patterns (FDPs) lasting three beats. A redundancy reduction criterion is proposed to group FDPs in four categories according to the number and type or of heart period changes: a) no variation (0V); b) one variation (1V); and c) two like variations (2LV); 4) two unlike variations (2UV). We found that: 1) the SE decreased during tilt due to the increased percentage of missing patterns; 2) the regularity index increased during tilt and CR10 as patterns followed each other according to a more repetitive scheme; and 3) during CR10, SE and regularity index were not redundant as the regularity index significantly decreased while SE remained unchanged. Concerning pattern analysis we found that: a) at rest mainly three classes (0V, 1V, and 2LV) were detected; b) 0V patterns were more likely during tilt; c) 1V and 2LV patterns were more frequent during CR10; and d) 2UV patterns were more likely during CR20. The proposed approach based on quantification of complexity allows a full characterization of heart period dynamics and the identification of experimental conditions known to differently perturb cardiovascular regulation.

Heart rate variability in chronic heart failure.

The analysis of heart rate variability (HRV) provides information about autonomic cardiovascular control in healthy subjects. In the past 15 years, several articles have been published regarding HRV and chronic heart failure (CHF). The results of these papers substantially demonstrated that HRV is significantly different in CHF patients compared to controls. Moreover, some variables derived from HRV analysis showed significant independent prognostic capacity. In particular, the reduction of variance (expressed as SDNN) and low-frequency spectral component of HRV (ranging from 0.03 to 0.15 Hz) seem related to an increased mortality in CHF. Nevertheless, these variables are not yet considered in clinical practice. A better understanding of the physiopathological basis of the reported alterations of HRV in CHF patients is required in order to permit its use as a clinical tool for prognosis and tailored therapy in individual CHF patients.

[Heart rate variability]. / Variabilità della frequenza cardiaca.

In 1981 a study on heart rate variability (HRV) and on the neural control of the heart was published in Science. Since then, the number of papers concerning this topic has increased exponentially. Some aspects of the relationship between HRV and the neural control of the cardiovascular system are now clear, for example: a decreased SDNN (a measure of variance) during a period of 24 hours is a well established independent negative prognostic factor after acute myocardial infarction and in chronic heart failure patients. Moreover, an increased sympathetic modulation elicited by standard laboratory maneuvers determines an increased power of the low frequency (LF) spectral component (0.03-0.15 Hz), expressed in normalized units. Nevertheless, the interpretation of the oscillatory components present in HRV, particularly in pathophysiological conditions, is far from being clear. The influence of several neurohumoral circuits can induce various changes in HRV according to different physiological or pathological conditions. A new approach to the study of HRV called "information domain" might help to obtain some more information about HRV. Furthermore, in the future, HRV analysis might be useful when deciding on the best pharmacological combination for the individual patient and for the probabilistic prediction of acute cardiac events.

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.

Comparison of low-dose dobutamine ventriculography with low-dose dobutamine echocardiography for predicting regional improvement in left ventricular function after coronary artery bypass grafting.

The demonstration of a contractile reserve during low-dose dobutamine echocardiography (LDDE) identifies viable myocardium and predicts recovery of left ventricular (LV) function after myocardial revascularization in patients with chronic coronary artery disease. However, a technically difficult transthoracic visualization may limit the use of LDDE, thus requiring an alternative diagnostic procedure. The present study compares LDDE with low-dose dobutamine ventriculography (LDDV) in predicting an improvement in regional LV function after surgical revascularization. We studied 18 patients with coronary artery disease and LV dysfunction who were to undergo coronary artery bypass grafting. Preoperatively, all patients were evaluated for the presence of viable myocardium using LDDE and LDDV. Follow-up echocardiography at rest and left ventriculography were performed 4 months after successful revascularization to assess recovery of LV function. The sensitivity and specificity of LDDE to identify dysfunctional segments capable of recovering function were 63% and 71%, respectively, with a diagnostic accuracy of 68%. The sensitivity, specificity, and diagnostic accuracy of LDDE improved to 81%, 72%, and 76% when patients with optimal transthoracic evaluation were selected, whereas they were 30%, 77%, and 57%, respectively, in those who underwent suboptimal evaluation. The sensitivity, specificity, and diagnostic accuracy of LDDV were 66%, 75%, and 71%, respectively, with no difference in subgroups of patients. This study demonstrates that LDDV can be considered a useful technique for identifying the presence of myocardial viability and may provide an advantage over LDDE in patients with suboptimal echocardiographic visualization.

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.

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.

Linear and non-linear 24 h heart rate variability in chronic heart failure.

It has recently been demonstrated that SDNN of heart rate variability (HRV) is a useful independent prognostic tool in chronic heart failure (CHF). The purpose of the present study was to evaluate if spectral and non-linear analysis of 24-h HRV, considered markers of autonomic cardiac modulation, contain independent prognostic information in CHF patients. Twenty normal subjects and thirty consecutive outpatients with clinically stable CHF were studied for 2 years. Periods of 300 R-R intervals were analyzed from Holter recordings. The power spectral analysis, the slope of the linear relationship between log-power versus log-frequency (1/f), and the complexity content (using corrected conditional entropy; CCE) of the R-R series were calculated. The normalized power of the low frequency spectral component (LF) and the 1/f slope were significantly lower in patients compared to controls (respectively 30.1 +/- 3.0 vs. 48.6 +/- 3.4 and -1.27 +/- 0.04 vs. -1.08 +/- 0.05; P < 0.05). Moreover, the patients who died during the study presented a reduced LF (20.9 +/- 4.1 vs. 35.5 +/- 3.5 nu; P < 0.05) and a steeper 1/f slope (-1.40 +/- 0.09 vs. -1.21 +/- 0.04 nuts, P < 0.05) compared to survivors. These results remained significant in a logistic model including heart rate and SDNN. The information content present in spectral and non-linear analysis of HRV in CHF patients has prognostic relevance independently from the time domain measures of HRV. In particular, the reduction of LF power seems the best indicator among those considered.

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.

Individual recognition by heart rate variability of two different autonomic profiles related to posture.

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

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.