Cardiovascular regulation during sleep quantified by symbolic coupling traces.

Sleep is a complex regulated process with short periods of wakefulness and different sleep stages. These sleep stages modulate autonomous functions such as blood pressure and heart rate. The method of symbolic coupling traces (SCT) is used to analyze and quantify time-delayed coupling of these measurements during different sleep stages. The symbolic coupling traces, defined as the symmetric and diametric traces of the bivariate word distribution matrix, allow the quantification of time-delayed coupling. In this paper, the method is applied to heart rate and systolic blood pressure time series during different sleep stages for healthy controls as well as for normotensive and hypertensive patients with sleep apneas. Using the SCT, significant different cardiovascular mechanisms not only between the deep sleep and the other sleep stages but also between healthy subjects and patients can be revealed. The SCT method is applied to model systems, compared with established methods, such as cross correlation, mutual information, and cross recurrence analysis and demonstrates its advantages especially for nonstationary physiological data. As a result, SCT proves to be more specific in detecting delays of directional interactions than standard coupling analysis methods and yields additional information which cannot be measured by standard parameters of heart rate and blood pressure variability. The proposed method may help to indicate the pathological changes in cardiovascular regulation and also the effects of continuous positive airway pressure therapy on the cardiovascular system.

Modeling the cardiovascular system using a nonlinear additive autoregressive model with exogenous input.

The parameters of heart rate variability and blood pressure variability have proved to be useful analytical tools in cardiovascular physics and medicine. Model-based analysis of these variabilities additionally leads to new prognostic information about mechanisms behind regulations in the cardiovascular system. In this paper, we analyze the complex interaction between heart rate, systolic blood pressure, and respiration by nonparametric fitted nonlinear additive autoregressive models with external inputs. Therefore, we consider measurements of healthy persons and patients suffering from obstructive sleep apnea syndrome (OSAS), with and without hypertension. It is shown that the proposed nonlinear models are capable of describing short-term fluctuations in heart rate as well as systolic blood pressure significantly better than similar linear ones, which confirms the assumption of nonlinear controlled heart rate and blood pressure. Furthermore, the comparison of the nonlinear and linear approaches reveals that the heart rate and blood pressure variability in healthy subjects is caused by a higher level of noise as well as nonlinearity than in patients suffering from OSAS. The residue analysis points at a further source of heart rate and blood pressure variability in healthy subjects, in addition to heart rate, systolic blood pressure, and respiration. Comparison of the nonlinear models within and among the different groups of subjects suggests the ability to discriminate the cohorts that could lead to a stratification of hypertension risk in OSAS patients.

Seroprevalence of human granulocytic anaplasmosis in Berlin/Brandenburg, Germany: an 8-year survey.

This study investigated the seroprevalence of antibodies against Anaplasma phagocytophilum in Berlin/Brandenburg, north-eastern Germany. During 1994-2001, 422 sera from patients with proven tick-exposure (specimens with antibodies against Borrelia burgdorferi) were compared with 249 control sera. Using indirect fluorescent antibody testing, significantly more positive samples were detected among Borrelia antibody-positive specimens (4.5%, 95% CI 2.5-6.5%) than among controls (1.2%, 95% CI 0.5-1.9%; p < 0.05). While six (2.2%, 95% CI 1.3-3.1%) samples were positive among Borrelia antibody-positive sera between 1994 and 1997, 13 (8.7%, 95% CI 6.9-10.5%) were positive between 1998 and 2001 (p < 0.01), indicating an uneven annual seroprevalence.

Camera-based photoplethysmography in critical care patients.

BACKGROUND: Camera-based photoplethysmography (cbPPG) is an optical measurement technique that reveals pulsatile blood flow in cutaneous microcirculation from a distance. cbPPG has been shown to reflect pivotal haemodynamic events like cardiac ejection in healthy subjects. In addition, it provides valuable insight into intrinsic microcirculatory regulation as it yields dynamic, two-dimensional perfusion maps. In this study, we evaluate the feasibility of a clinical cbPPG application in critical care patients. METHODS: A mobile camera set-up to record faces of patients at the bed site was constructed. Videos were made during the immediate recovery after cardiac surgery under standard critical care conditions and were processed offline. Major motion artefacts were detected using an optical flow technique and suitable facial regions were manually annotated. cbPPG signals were highpass filtered and Fourier spectra out of consecutive 10s signal segments calculated for heart rate detection. Signal-to-noise ratios (SNR) of the Fourier spectra were derived as a quality measure. Reference data of vital parameters were synchronously acquired from the bed site monitoring system. RESULTS: Seventy patient videos of an average time of 28.6±2.8 min were analysed. Heart rate (HR) was detected within a±5 bpm range compared to reference in 83% of total recording time. Low SNR and HR detection failure were mostly, but not exclusively, attributed to non-physiological events like patient motion, interventions or sudden changes of illumination. SNR was reduced by low arterial blood pressure, whereas no impact of other perioperative or disease-related parameters was identified. CONCLUSION: Cardiac ejection is detectable by cbPPG under pathophysiologic conditions of cardiovascular disease and perioperative medicine. cbPPG measurements can be seamlessly integrated into the clinical work flow of critical care patients.

Baroreflex sensitivity, heart rate, and blood pressure variability in normal pregnancy.

Heart rate variability is a relevant predictor of cardiovascular risk in humans. However, to use heart and blood pressure (BP) variability or baroreflex sensitivity as markers for hypertensive pregnancy disorders, it is first necessary to describe these parameters in normal pregnancy. To accommodate the complexities of autonomic cardiovascular control we added parameter domains of nonlinear dynamics to conventional linear methods of time and frequency domains. The BP of 27 women with normal pregnancy and 14 nonpregnant women were monitored at a high resolution (200 Hz sampling frequency) using a Portapres for 30 min. The pregnant women were divided into groups of 32 or less or greater than 32 weeks of gestation. Pregnant and nonpregnant women were classified into subclasses of maternal age of less than 28 or 28 or more years. Except for two single parameter domains, we found no significant differences in heart rate and BP variability for pregnant women with different gestational age or different maternal age. Moreover, no significant differences in spontaneous baroreflex sensitivity could be found between pregnant women regardless of either their age or gestational age. In contrast, all measures of nonlinear dynamics of heart rate variability as well as all parameter domains of spontaneous baroreflex sensitivity showed significant changes between pregnant and nonpregnant women, whereas BP variability did not differ between those groups. This complex assessment of autonomic cardiovascular regulation has shown that the parameters tested are stable in the second half of normal pregnancy, and might have the potential to be excellent indicators of pathophysiologic conditions.

Impairment of cardiovascular autonomic control in patients early after cardiac surgery.

OBJECTIVE: Impairment of the baroreceptor reflex activity reflects an alteration of the autonomous regulation of the cardiovascular system and has proven to predict fatal outcome in patients after acute myocardial infarction. The following study was performed to analyse the baroreceptor sensitivity, heart rate variability and blood pressure variability in patients early after coronary surgery. METHODS: Twenty-five male patients undergoing coronary artery bypass were examined in a prospective study; normal values were obtained from healthy volunteers. Arterial pressure signals were recorded from a radial artery catheter for 30 min preoperatively and in short intervals after surgery. Mechanical manipulations and pharmacological interventions were avoided during the sampling periods. Baroreflex function was calculated according to the dual sequence method, heart rate variability and blood pressure variability were calculated including nonlinear methods. RESULTS: Initial values of the patients did not differ from healthy volunteers. The strength of baroreflex sensitivity (increase in blood pressure causing a synchronous decrease of heart rate) is low 2 h postoperatively. The number of delayed tachycardic changes of heart rate, which are caused by sympathetic activation, is only moderately reduced as compared to values obtained from healthy volunteers. Heart rate variability is widely unchanged as compared to preoperative values; blood pressure variability showed an increase of low-frequency components, again indicating sympathetic predominance. Nonlinear analyses revealed reduced system complexity at the beginning of the postoperative course. CONCLUSION: Obviously, there is a vagal suppression 20 h after surgery, while the sympathetic tonus works in a normal range. This unbalanced interaction of the autonomous systems is similar to findings in patients after myocardial infarction. The predictive value of these markers has to be elucidated in further clinical studies.

Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene.

Heart rate variability is a relevant predictor of cardiovascular risk in humans. A significant genetic influence on heart rate variability is suggested, although the genes involved are ill-defined. The Mas-protooncogene encodes a G-protein-coupled receptor with seven transmembrane domains highly expressed in testis and brain. Since this receptor is supposed to interact with the signaling of angiotensin II, which is an important regulator of cardiovascular homeostasis, heart rate and blood pressure were analyzed in Mas-deficient mice. Using a femoral catheter the blood pressure of mice was measured for a period of 30 min and 250 data values per second were recorded. The mean values and range of heart rate and blood pressure were then calculated. Neither heart rate nor blood pressure were significantly different between knockout mice and controls. However, high resolution recording of these parameters and analysis of the data by non-linear dynamics revealed significant alterations in cardiovascular variability in Mas-deficient animals. In particular, females showed a strong reduction of heart rate variability. Furthermore, the data showed an increased sympathetic tone in knockout animals of both genders. The marked alterations detected in Mas-deficient mice of both genders suggest that the Mas-protooncogene is an important determinant of heart rate and blood pressure variability.

[Analysis of cardiovascular regulation after heart operation]. / Analyse der kardiovaskulären Regulation nach Herzoperation.

Baroreflex sensitivity, heart rate and blood pressure variability have been proven to predict fatal outcome in patients after acute myocardial infarction. This study aims at investigating the time dependent alterations in cardiovascular control to find new predictive parameters for arrhythmic events after surgery. 25 male patients with coronary heart disease following an aortocoronary bypass surgery were examined. The results show significant alterations in sympathetic and vagal mediated regulation. The extubation after 6 hours seems to influence primarily the sympathetic activation. Obviously, there is a vagal suppression 20 h after surgery, while the sympathetic tonus works in a normal range. This unbalanced interaction of the autonomous system seems to be a reason for the high incidence of atrial tachycardias in the early period after cardiac surgery.

Model based analysis of the heart rate and blood pressure relationship.

The main intention of this contribution is to measure the coupling between bivariate time series using the dual sequence method to estimate the baroreflex as well as a nonlinear regression approach, namely the maximal correlation method, to get a better understanding of the underlying processes. The data we analyse are heart rate and blood pressure variability time series from 27 patients with dilated cardiomyopathy as well as from a control group of 27 age- and sex-matched healthy subjects. The results strongly indicate and confirm the mechanisms of respiratory sinus arrhythmia in heart rate. Revealing the coupling direction and the strength of coupling between heart rate and blood pressure via optimal transformations in addition to the baroreflex estimation seems to be a very promising approach.

[A modular method for automated evaluation of gait analysis data]. / Ein modulares Verfahren zur automatisierten Auswertung von Ganganalysedaten.

A modular methodology for automated gait data evaluation: The aim of Instrumented Gait Analysis is to measure data such as joint kinematics or kinetics during gait in a quantitative way. The data evaluation for clinical purposes is often performed by experienced physicians (diagnosis of specific motion dysfunction, planning and validation of therapy). Due to subjective evaluation and complexity of the pathologies, there exists no objective, standardized data analysis method for these tasks. This article covers the development of a modular, computer-based methodology to quantify the degree of pathological gait in comparison to normal behavior, as well as to automatically search for interpretable gait abnormalities and to visualize the results. The outcomes are demonstrated with two different patient groups.

Effect of CPAP therapy on daytime cardiovascular regulations in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence that causes pathological changes in cardiovascular regulation during the night and also during daytime. We investigated whether the treatment of OSA at night by means of continuous positive airway pressure (CPAP) improves the daytime consequences. Twenty-eight patients with OSA, 18 with arterial hypertension, 10 with normal blood pressure, were investigated at baseline and with three months of CPAP treatment. Ten age and sex matched healthy control subjects were investigated for comparisons. We recorded a resting period with 20min quiet breathing and an exercise stress test during daytime with ECG and blood pressure (Portapres). The bicycle ergometry showed a significant reduction of the diastolic blood pressure at a work load of 50W and 100W (p<0.05 and p<0.01, respectively) and a decrease of the heart rate recovery time after the stress test (p<0.05). These results indicate a reduction of vascular resistance and sympathetic activity during daytime. The coupling analysis of the resting periods by means of symbolic coupling traces approach indicated an effect of the CPAP therapy on the baroreflex reaction in hypertensive patients where influences of the systolic blood pressure on the heart rate changed from pathological patterns to adaptive mechanisms of the normotensive patients (p<0.05).

Effects of awareness and nociception on heart rate variability during general anaesthesia.

During anaesthesia awareness and nociception are serious complications that may further lead to haemodynamic instability. Specific monitoring of depth of hypnosis and depth of analgesia based on heart rate variability (HRV) analysis is eligible to improve patient safety and reduce efforts in post-operative care. Consequently, in this analysis we assess the applicability of HRV parameters during surgical interventions with standardized intravenous propofol-remifentanil-anaesthesia. Peri-operative electrocardiograms were recorded from cardiovascular stable patients (ASA Score I/II, N = 32, age: 36.4 ± 11.23 a, BMI: 25.2 ± 3.16) scheduled for trauma and dentofacial surgery. HRV time- and frequency-domain parameters, measures of complexity and nonlinear dynamics were compared by analysing longitudinally distributed 300 s intervals preceding/following induction of anaesthesia (BL-I1), intubation (I1-I2) and extubation (E1-E2). Mean value (meanNN) and standard deviation (sdNN) of the heart rate are influenced in BL-I1 (p < 0.001), I1-I2 (p < 0.05) and E1-E2 (p < 0.001). The number of forbidden words of symbolic dynamics changes significantly for BL-I1 (p < 0.001) and not for I1-I2 and E1-E2 (p > 0.05). Probability of low-variability POLVAR10 is significantly altered in all comparisons (BL-I1: Δ = 0.032, p < 0.01, I1-I2: Δ = 0.12, p < 0.05, E1-E2: Δ = 0.169, p < 0.01) but especially during nociception. While standard time-domain parameters lacked selectivity, parameters of symbolic dynamics appear to be specifically influenced by changes in depth of hypnosis and nociception, respectively. However, the lack of steady-state ventilation/breathing in this study needs to be considered in future research. To be used for clinical anaesthesia monitoring our results have to be prospectively validated in clinical studies.

Symbolic coupling traces for causality analysis of cardiovascular control.

Directional coupling analysis of time series is an important subject of current research. In this paper, a method based on symbolic dynamics for the detection of time-delayed coupling in biosignals is presented. The symbolic coupling traces, defined as the symmetric and diametric traces of the bivariate word distribution, allow for a more reliable quantification of coupling and are compared with established methods like mutual information and cross recurrence analysis. The symbolic coupling traces method is applied to appropriate model systems and cardiological data which demonstrate its advantages especially for nonstationary and noisy data. Moreover, the method of symbolic coupling traces is used to analyze and quantify time-delayed coupling of cardiovascular measurements during different sleep stages. Significant different regulatory mechanisms are detected not only between the deep sleep and the other sleep stages but also between healthy subjects and patients. The proposed method may help to indicate pathological changes in cardiovascular regulation and also effects of continuous positive airway pressure therapy on the cardiovascular system.

The angiotensin-(1-7) receptor agonist AVE0991 dominates the circadian rhythm and baroreflex in spontaneously hypertensive rats.

Because we previously suggested the endogenous heptapeptide angiotensin (Ang)-(1-7) to be involved in the improvement of baroreflex sensitivity observed in spontaneously hypertensive rats (SHR), we here investigated the role of the heptapeptide in blood pressure control under physiologic conditions in awake SHR using the first nonpeptide, orally applicable Ang-(1-7) receptor agonist AVE0991 by telemetry. Five weeks after the start of treatment the blood pressure signals (500 Hz) were monitored in 10 untreated and 6 age-matched male SHR treated by AVE0991 for 24 hours (every 2 hours for 10 minutes). The autonomous tone was estimated from the heart rate and blood pressure variability (HRV, BPV) and from the spontaneous baroreceptor sensitivity (BRS).AVE0991 treatment blunted the rodent-characterizing nightly increase in blood pressure and led to pronounced changes in the BPV and HRV parameters during the night in comparison to untreated controls (eg, sdNN: AVE0991=8.19 versus control=11.5 mm Hg; P<0.001). However, even more significant differences were detected for BRS. Whereas the average slope did not alter, the activation of the baroreflexes (P<10E-6) and the number of baroreflex fluctuations were reduced dramatically by AVE0991 (P<10E-5). The data obtained pointed to an abating impact of AVE0991 on the baroreceptor in SHR and to its influence on the circadian rhythm, thus implying a direct involvement of Ang-(1-7) in cardiovascular control.

Analysis of cardiovascular oscillations: a new approach to the early prediction of pre-eclampsia.

Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.

[Dual sequence method for analysis of spontaneous baroreceptor reflex sensitivity in patients with dilated cardiomyopathy]. / Duale Sequenzmethode zur Analyse der spontanen Baroreflexsensitivität bei Patienten mit dilatativer Kardiomyopathie.

The analysis of heart rate variability (HRV) and blood pressure variability (BPV) improves the characterization of patients with dilated cardiomyopathy (DCM). In this study we tested the hypothesis that patients with DCM and controls show a different behavior in the baroreflex (BR) regulation. In contrast to other methods, the new dual sequence method (DSM) analyzes the baroreflex sensitivity (BRS) as a response of the heart rate (interbeat interval, IBI) on dual spontaneous fluctuations of blood pressure (BP). The DSM includes the analysis of bradycardiac fluctuations (an increase of BP causes an increase of IBI) and tachycardiac fluctuations (decrease of BP causes a decrease of IBI) to obtain enhanced information about the sympathetic-vagal regulation. DCM patients show a 40-50% lower number of correlated blood pressure-heart rate fluctuations (DCM patients: male 154 +/- 93, female 93 +/- 40 vs. control group: m 245 +/- 112, f 150 +/- 55, p < 0.05). The BRS in DCM patients is significantly lower than in controls (5.2 +/- 1.9 vs. 8.0 +/- 5.4 (ms/mm Hg), p < 0.05). Using the DSM the discriminant function analysis (6 parameters) classifies correctly 84% of DCM patients and the control group. Using the classical sequence method, only 76% were correctly classified. The DSM is a useful method for analyzing the BRS based on the spontaneous BR to obtain an increased classification of patients with DCM. BRS in patients with DCM is significantly reduced and apparently more ineffective.