Effects of Supplemental Oxygen on Cardiovascular and Respiratory Interactions by Extended Partial Directed Coherence in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and restrictive disease characterized by fibrosis and inflammatory changes in lung tissue producing a reduction in diffusion capacity and leading to exertional chronic arterial hypoxemia and dyspnea. Furthermore, clinically, supplemental oxygen (SupplO2) has been prescribed to IPF patients to improve symptoms. However, the evidence about the benefits or disadvantages of oxygen supplementation is not conclusive. In addition, the impact of SupplO2 on the autonomic nervous system (ANS) regulation in respiratory diseases needs to be evaluated. In this study the interactions between cardiovascular and respiratory systems in IPF patients, during ambient air (AA) and SupplO2 breathing, are compared to those from a matched healthy group. Interactions were estimated by time series of successive beat-to-beat intervals (BBI), respiratory amplitude (RESP) at BBI onset, arterial systolic (SYS) and diastolic (DIA) blood pressures. The paper explores the Granger causality (GC) between systems in the frequency domain by the extended partial directed coherence (ePDC), considering instantaneous effects. Also, traditional linear and nonlinear markers as power in low (LF) and high frequency (HF) bands, symbolic dynamic indices as well as arterial baroreflex, were calculated. The results showed that for IPF during AA phase: 1) mean BBI and power of BBI-HF band, as well as mean respiratory frequency were significantly lower (p < 0.05) and higher (p < 0.001), respectively, indicating a strong sympathetic influence, and 2) the RESP → SYS interaction was characterized by Mayer waves and diminished RESP → BBI, i.e., decreased respiratory sinus arrhythmia. In contrast, during short-term SupplO2 phase: 1) oxygen might produce a negative influence on the systolic blood pressure variability, 2) the arterial baroreflex reduced significantly (p < 0.01) and 3) reduction of RSA reflected by RESP → BBI with simultaneous increase of Traube-Hering waves in RESP → SYS (p < 0.001), reflected increased sympathetic modulation to the vessels. The results gathered in this study may be helpful in the management of the administration of SupplO2.

Hemodynamic response to low-flow acute supplemental oxygen in idiopathic pulmonary fibrosis and elderly healthy subjects.

BACKGROUND: Hemodynamic response to supplemental oxygen in idiopathic pulmonary fibrosis (IPF) is still not well known. OBJECTIVE: To determine and compare the effect of low-flow acute supplemental oxygen on the hemodynamics of IPF patients and matched healthy subjects. METHODS: Descriptive and comparative study in 20 IPF-patients and 19 Control-subjects, (60-80 years old) breathing ambient air followed by acute nasal low-flow (3 L/min) supplemental oxygen. Non-invasive methods were used during the supine position to evaluate oxygen saturation, heart rate, stroke volume index, cardiac output index, total peripheral resistance and arterial blood pressure. RESULTS: Breathing ambient air, IPF (vs. Control) presented lower values in stroke volume index (38.7 [29.4-43.2] vs. 45.4 [38.4-50.9] mL•kg-1•m2; p=0.009) and cardiac output index (2.484 [2.268 - 2.946] vs. 2.857 [2.628 - 3.054] L•min-1•m-2; p=0.028), with higher total peripheral resistance (1644 [1559-2076] vs. 1505 [1366-1784] dyne•s•cm-5; p=0.017). During supplemental oxygen (vs. ambient air), both groups increased oxygen saturation above 94% (p<0.001) while heart rate decreased about 6 to 8% (p<0.001); stroke volume index increased around 7% in the Control-group (p=0.004) but only 1% in the IPF-group (p=0.017). In addition, IPF showed increments in total peripheral resistance (1644 [1559-2076] vs. 1706 [1554-2278] dyne•s•cm-5; p=0.017) with subsequent decrements in cardiac output index (2.484 [2.268 - 2.946] vs. 2.362 [2.139 - 2.664] L•min-1•m-2; p<0.001). CONCLUSION: Low-flow acute supplemental oxygen in IPF causes a meaningful decrement in cardiac output due to greater reduction in heart rate and increment in total peripheral resistance than matched healthy subjects. Knowing the hemodynamic profile of IPF patients may be helpful in determining their management with supplemental oxygen.

Time-Frequency Analysis of Cardiovascular and Cardiorespiratory Interactions During Orthostatic Stress by Extended Partial Directed Coherence.

In this study, the linear method of extended partial directed coherence (ePDC) was applied to establish the temporal dynamic behavior of cardiovascular and cardiorespiratory interactions during orthostatic stress at a 70° head-up tilt (HUT) test on young age-matched healthy subjects and patients with orthostatic intolerance (OI), both male and female. Twenty 5-min windows were used to analyze the minute-wise progression of interactions from 5 min in a supine position (baseline, BL) until 18 min of the orthostatic phase (OP) without including pre-syncopal phases. Gender differences in controls were present in cardiorespiratory interactions during OP without compromised autonomic regulation. However in patients, analysis by ePDC revealed considerable dynamic alterations within cardiovascular and cardiorespiratory interactions over the temporal course during the HUT test. Considering the young female patients with OI, the information flow from heart rate to systolic blood pressure (mechanical modulation) was already increased before the tilt-up, the information flow from systolic blood pressure to heart rate (neural baroreflex) increased during OP, while the information flow from respiration to heart rate (respiratory sinus arrhythmia) decreased during the complete HUT test. Findings revealed impaired cardiovascular interactions in patients with orthostatic intolerance and confirmed the usefulness of ePDC for causality analysis.

Detection of Respiratory Crackle Sounds via an Android Smartphone-based System.

Pulmonary auscultation with traditional stethoscope, although useful, has limitations for detecting discontinuous adventitious respiratory sounds (crackles) that commonly occur in respiratory diseases. In this work, we present the development of a mobile health system for the automated detection of crackle sounds, comprised by an acoustical sensor, a smart phone device, and a mobile application (app) implemented in Android. The app allows the physician to record, store, reproduce, and analyze respiratory sounds directly on the smart phone. The algorithm for crackle detection was based on a time-varying autoregressive modeling. Performance of the automated detector was analyzed using synthetic fine and coarse crackle sounds randomly added to the basal respiratory sounds acquired from healthy subjects with different signal to noise ratios. Accuracy and sensitivity were found to range from 90.7% to 94.0% and from 91.2% to 94.2%, respectively. Application of the proposed mobile system to real acquired data from a patient with pulmonary fibrosis is also exemplified.

Dynamics of the cardiovascular autonomic regulation during orthostatic challenge is more relaxed in women.

Linear dynamic analysis of cardiovascular and respiratory time series was performed in healthy subjects with respect to gender by shifted short-term segments throughout a head-up tilt (HUT) test. Beat-to-beat intervals (BBI), systolic (SYS) and diastolic (DIA) blood pressure and respiratory interval (RESP) time series were acquired in 14 men and 15 women. In time domain (TD), the descending slope of the auto-correlation function (ACF) (BBI_a31cor) was more pronounced in women than in men (p<0.05) during the HUT test and considerably steeper (p<0.01) at the end of orthostatic phase (OP). The index SYS_meanNN was slightly but significantly lower (p<0.05) in women during the complete test, while higher respiratory frequency and variability (RESP_sdNN) were found in women (p<0.05), during 10-20 min after tilt-up. In frequency domain (FD), during baseline (BL), BBI-normalized low frequency (BBI_LFN) and BBI_LF/HF were slightly but significantly lower (p<0.05), while normalized high frequency (BBI_HFN) was significantly higher in women. These differences were highly significant from the first 5 min after tilt-up (p<0.01) and highly significant (p<0.001) during 10-14 min of OP. Findings revealed that men showed instantaneously a pronounced and sustained increase in sympathetic activity to compensate orthostatism. In women, sympathetic activity was just increased slightly with delayed onset without considerably affecting sympatho-vagal balance.

Temporal Analysis of Cardiovascular and Respiratory Complexity by Multiscale Entropy Based on Symbolic Dynamics.

The effect of an orthostatic stress on cardiovascular and respiratory complexity was investigated to detect impaired autonomic regulation in patients with vasovagal syncope (VVS). A total of 16 female patients and 12 age-matched healthy female subjects were enrolled in a passive 70° head-up tilt test. Also, 12 age-matched healthy male subjects were enrolled to study gender differences. Analysis was performed dynamically using various short-term (5 min) windows shifted by 1 min as well as by 20 min of orthostatic phase (OP) to evaluate local and global complexity. Complexity was determined over multiple time scales by the established method of refined composite multiscale entropy (RCMSE) and by a new proposed method of multiscale entropy based on symbolic dynamics (MSE-SD). Concerning heart rate variability (HRV) during OP, both methods revealed the highest complexity for female controls followed by lower complexity in male controls (p < 0.01) and by the lowest complexity in female patients (p < 0.01). For blood pressure variability (BPV), no gender differences in controls were shown by any method. However, MSE-SD demonstrated highly significantly increased BPV complexity in patients during OP (p < 0.01 on 4 time-scales after 7 min, p < 0.001 on 5 time-scales after 11 min) while RCMSE did not reveal considerable differences (p < 0.05 on 2 time scales after 7 min). Respiratory complexity was further increased in patients primary shown by MSE-SD. Findings indicated impaired autonomic regulation in VVS patients characterized by predominantly increased BPV complexity accompanied with decreased HRV complexity. In addition, results suggested extending the concept of complexity loss with disease.

Improvement of circadian rhythm of heart rate variability by eurythmy therapy training.

Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep.

Autonomic Regulation during Quiet and Active Sleep States in Very Preterm Neonates.

The immature autonomic nervous system (ANS) in premature infants regulates heart rate (HR) and respiration different during quiet sleep (QS) and active sleep (AS). Little information is available about ANS regulation in these subjects. The aim of this study was to investigate changes in autonomic regulation and cardiorespiratory coupling during AS and QS in five very preterm neonates with gestational age (GA) 26-31 weeks, applying univariate and bivariate linear and non-linear dynamics methods to the recorded cardiorespiratory signals. During QS univariate linear indices revealed lower standard deviations and entropies, indicating decreased heart rate (HR) variability. More balanced sympatho-vagal behavior of the ANS was revealed by decreased low frequency (LF), increased high frequency (HF), and a trend toward lower ratio LF/HF in QS. Applied non-linear indices (probabilities, entropies, and fractal measures) quantifying the complexity and scaling behavior of HR regulation processes were significantly altered in QS in comparison to AS. This reflects a lower short-term variability, less complexity, and a loss of fractal-like correlation properties of HR dynamics in QS. One major finding is that cardiorespiratory coupling is not yet completely developed in very preterm neonates with 26-31 weeks GA. Significantly different regulation patterns in bivariate oscillations of HR and respiration during AS and QS could be recognized. These patterns were characterized on the one hand by predominant monotonous regulating sequences originating from respiration independently from HR time series in AS, and to a minor degree in QS, and on the other hand by some prominent HR regulation sequences in QS independent of respiratory regulation. We speculate that these findings might be suitable for monitoring preterm neonates and for detecting disorders in the developing cardiorespiratory system.

Improvement of heart rate variability by eurythmy therapy after a 6-week eurythmy therapy training.

BACKGROUND: Eurythmy therapy (EYT) is a mind-body therapy used in anthroposophic medicine. Recently, the authors were able to show that at comparable workloads, EYT stimulated heart rate variability (HRV) whereas conventional ergometer training attenuated HRV. Furthermore, a long-term improvement of quality of life (QoL) and stress coping strategies by EYT could be shown. OBJECTIVE: This study aimed to evaluate the long-term effects of EYT training on HRV. DESIGN: A total of 23 healthy women (mean age = 44.57 ± 8.04 years) performed 10 hours of EYT over a period of 6 weeks. Electrocardiograms were recorded before and after the EYT trial. HRV was quantified by the extent of high (HF), low (LF), very low (VLF), and ultra low frequency (ULF) oscillations of heart rate. RESULTS: Autonomic regulation was significantly changed following the EYT training compared with baseline. Especially the proportion referring to the total power (P) of HF/P and LF/P increased, whereas ULF/P and (ULF+VLF)/P decreased after the training period. CONCLUSION: EYT shifted the autonomic regulation proportionally referring to the total power mainly caused by changes of ULF and VLF components of HRV. The LF and HF spectral components were also decreased following EYT while their proportion in relation to the total variance of the power spectrum was increased. The proportional enhancement of the higher frequency and the decrease of the ULF and VLF components are probably an indicator of an improvement of autonomic regulation processes by more relaxed physical activity after the EYT training, thus supporting the plausibility of the improved QoL and better stress coping strategies.

Quantification of compensatory processes of postnatal hypoxia in newborn piglets applying short-term nonlinear dynamics analysis.

BACKGROUND: Newborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adapting their vital functions. Exposure to hypoxia leads to an increase in the sympathetic tone causing cardio-respiratory response, peripheral vasoconstriction and vasodilatation in privileged organs like the heart and brain. However, there is only limited information available about the time and intensity changes of the underlying complex processes controlled by the autonomic nervous system. METHODS: In this study an animal model involving seven piglets was used to examine an induced state of circulatory redistribution caused by moderate oxygen deficit. In addition to the main focus on the complex dynamics occurring during sustained normocapnic hypoxia, the development of autonomic regulation after induced reoxygenation had been analysed. For this purpose, we first introduced a new algorithm to prove stationary conditions in short-term time series. Then we investigated a multitude of indices from heart rate and blood pressure variability and from bivariate interactions, also analysing respiration signals, to quantify the complexity of vegetative oscillations influenced by hypoxia. RESULTS: The results demonstrated that normocapnic hypoxia causes an initial increase in cardiovascular complexity and variability, which decreases during moderate hypoxia lasting one hour (p < 0.004). After reoxygenation, cardiovascular complexity parameters returned to pre-hypoxic values (p < 0.003), however not respiratory-related complexity parameters. CONCLUSIONS: In conclusion, indices from linear and nonlinear dynamics reflect considerable temporal changes of complexity in autonomous cardio-respiratory regulation due to normocapnic hypoxia shortly after birth. These findings might be suitable for non-invasive clinical monitoring of hypoxia-induced changes of autonomic regulation in newborn humans.

Discrimination and characterization of breath from smokers and non-smokers via electronic nose and GC/MS analysis.

The objective of this study was to prove the general applicability of an electronic nose for analyzing exhaled breath considering the dependency on smoking. At first, odor compounds from spices (n=6) were detected via the electronic nose and further characterized and classified with gas chromatography/ mass spectrometry to demonstrate the principle ability of the electronic nose. Then, the exhaled breath from smokers and non-smokers were analyzed to prove the influence of smoking on breath analyses with the electronic nose. The exhaled breath was sampled from 11 smokers and 11 non-smokers in a special sampling bag with the mounted sensor chip of the electronic nose. Additionally, solid phase micro-extraction (SPME) technique was established for detection of the specific chemical compounds with gas chromatography and mass spectrometry (GC/MS). For analyses of the sensor signals the principle component analysis (PCA) was applied and the groups were differentiated by linear discriminant function analysis. In accordance to the discrimination between the different spices and between smokers and non-smokers the PCA analysis leads to an optimum accuracy of 100%. The results of this study show that an electronic nose has the ability to detect different changes of odor components and provides separation of smoking side effects in smelling different diseases.