Pulse wave amplitude and heart period variability in children with upper airway obstruction.

OBJECTIVE: The aim of this study was to assess cardiovascular autonomic modulation in children with upper airway obstruction (UAO), to compare this modulation to that of non-snoring children and to investigate the effect of adenotonsillectomy (AT). METHODS: ECG and finger photoplethysmographic signals obtained from overnight polysomnographic (PSG) recordings of 31 children with mild-to-moderate UAO and 34 non-snoring children were analysed. The extent of autonomic modulation was assessed by symbolic analysis of heart period (HP), pulse wave amplitude (PWA), and their joint dynamics during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. RESULTS: Children with UAO showed more frequent patterns of monotonically increasing and decreasing HP in NREM sleep and monotonically increasing and decreasing joint PWA-HP patterns in REM and NREM sleep at baseline compared to controls, even when considering only periods of sleep free of discrete respiratory events. Following AT, HP, and joint PWA-HP dynamics significantly altered towards levels observed in the control group. CONCLUSIONS: In children with mild-to-moderate UAO, cardiovascular autonomic modulation is more prevalent, even during quiet, event-free sleep. AT appears to reverse this pattern.

T-wave morphology can distinguish healthy controls from LQTS patients.

Long QT syndrome (LQTS) is an inherited disorder associated with prolongation of the QT/QTc interval on the surface electrocardiogram (ECG) and a markedly increased risk of sudden cardiac death due to cardiac arrhythmias. Up to 25% of genotype-positive LQTS patients have QT/QTc intervals in the normal range. These patients are, however, still at increased risk of life-threatening events compared to their genotype-negative siblings. Previous studies have shown that analysis of T-wave morphology may enhance discrimination between control and LQTS patients. In this study we tested the hypothesis that automated analysis of T-wave morphology from Holter ECG recordings could distinguish between control and LQTS patients with QTc values in the range 400-450 ms. Holter ECGs were obtained from the Telemetric and Holter ECG Warehouse (THEW) database. Frequency binned averaged ECG waveforms were obtained and extracted T-waves were fitted with a combination of 3 sigmoid functions (upslope, downslope and switch) or two 9th order polynomial functions (upslope and downslope). Neural network classifiers, based on parameters obtained from the sigmoid or polynomial fits to the 1 Hz and 1.3 Hz ECG waveforms, were able to achieve up to 92% discrimination between control and LQTS patients and 88% discrimination between LQTS1 and LQTS2 patients. When we analysed a subgroup of subjects with normal QT intervals (400-450 ms, 67 controls and 61 LQTS), T-wave morphology based parameters enabled 90% discrimination between control and LQTS patients, compared to only 71% when the groups were classified based on QTc alone. In summary, our Holter ECG analysis algorithms demonstrate the feasibility of using automated analysis of T-wave morphology to distinguish LQTS patients, even those with normal QTc, from healthy controls.

QT variability improves risk stratification in patients with dilated cardiomyopathy.

Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to improve the risk stratification applying a multivariate technique including QT variability (QTV). We enrolled and significantly separated 56 low risk and 13 high risk DCM patients by nearly all applied BPV and QTV methods, but not with traditional heart rate variability analysis. The optimum set of two indices calculating the multivariate discriminate analysis (DA) included one BPV index calculated by symbolic dynamics method (DBP(Shannon)) and one index calculated from QTV (QTV(log)) achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Performing only electrocardiogram analysis, the optimum multivariate approach including indices from segmented Poincaré plot analysis and QTV still achieved a remarkable AUC of 88.3%. Increasing the number of indices for multivariate DA up to three, we achieved an AUC of 95.7%, sensitivity of 100% and specificity of 85.7% including one clinical, one BPV and one QTV index. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach.

Beat-to-beat QT interval variability and T-wave amplitude in patients with myocardial infarction.

The purpose of this study was to investigate the effects of T-wave amplitude and ECG lead on beat-to-beat QT interval variability (QTV) in patients with myocardial infarction (MI) compared to healthy subjects. Standard resting 12-lead ECGs of 79 MI patients and 69 healthy subjects were investigated. Beat-to-beat QT intervals were measured separately for each lead using a template matching algorithm. In addition, we extracted the beat-to-beat T-wave amplitude in each lead. We computed the standard deviation of beat-to-beat QT intervals as a marker of QTV for both healthy subjects and MI patients. Significant QTV differences were observed between the 12 ECG leads as well as between the groups of healthy subjects and MI patients. Beat-to-beat QTV was significantly higher in MI patients than in healthy subjects for half of the leads. Furthermore, significant T-wave amplitude differences across leads and between groups were observed. A significant inverse relation between beat-to-beat QTV and T-wave amplitude was demonstrated. The group differences in QTV remained significant after co-varying for the T-wave amplitude. In conclusion, the increase in beat-to-beat QTV that has been repeatedly reported in patients with MI is partly due to the lower T-wave amplitudes. However, QTV remains significantly increased in MI patients after covarying for this effect.

Ondansetron prevents changes in respiratory pattern provoked by LiCl: a new approach for studying pro-emetic states in rodents?

There are a limited number of biological indices for assessing pro-emetic states in laboratory rodents as they do not possess the vomiting response. In the present study we tested the hypothesis that in rats, pro-emetic intervention would affect the respiratory pattern. To this end, using whole-body plethysmography, in adult male Wistar rats we recorded respiration after i.p. administration of either the emetic agent LiCl or Ringer. Quantification of respiratory signals (from 5 to 35 min post-injection) revealed that post-LiCl, mean respiratory rate was significantly lower (126 ± 9 vs. 178 ± 10 cpm, p < 0.005) and less variable (Kvar 59 ± 8% vs. 73 ± 3%; p<0.05) compared to the post-Ringer condition. Furthermore, while mode values of respiratory rate histograms did not differ between the treatments (indicating that the dominant respiratory frequency remained unchanged), LiCl reduced the fraction of time spent at high respiratory rate (>200 cpm) from 25 ± 3% to 9 ± 2% (p = 0.004). Thus, reduction of the mean respiratory rate by LiCl was predominantly due to reduced contribution of high-frequency breathing that is normally associated with motor activity and/or arousal. Non-linear multifractal analysis of respiratory signals revealed that post-LiCl, respiration becomes less random and more orderly. 5-HT3 antagonist ondansetron prevented respiratory changes elicited by LiCl. We conclude that the observed changes likely reflect effects of LiCl on animals' motion, and that this effect is mediated via 5-HT3 receptors. Providing that the effects observed in our study were quite robust, we suggest that simple and non-invasive respiratory monitoring may be a promising approach for studying emesis in rodents.

Multiscale time irreversibility of heart rate and blood pressure variability during orthostasis.

Time irreversibility is a characteristic feature of non-equilibrium, complex systems such as the cardiovascular control mediated by the autonomic nervous system (ANS). Time irreversibility analysis of heart rate variability (HRV) and blood pressure variability (BPV) represents a new approach to assess cardiovascular regulatory mechanisms. The aim of this paper was to assess the changes in HRV and BPV irreversibility during the active orthostatic test (a balance of ANS shifted towards sympathetic predominance) in 28 healthy young subjects. We used three different time irreversibility indices-Porta's, Guzik's and Ehler's indices (P%, G% and E, respectively) derived from data segments containing 1000 beat-to-beat intervals on four timescales. We observed an increase in the HRV and a decrease in the BPV irreversibility during standing compared to the supine position. The postural change in irreversibility was confirmed by surrogate data analysis. The differences were more evident in G% and E than P% and for higher scale factors. Statistical analysis showed a close relationship between G% and E. Contrary to this, the association between P% and G% and P% and E was not proven. We conclude that time irreversibility of beat-to-beat HRV and BPV is significantly altered during orthostasis, implicating involvement of the autonomous nervous system in its generation.

Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders.

Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

Altered interactions of heart rate and blood pressure during normal and abnormal pregnancy.

The assessment of the autonomic cardiovascular regulation provides important diagnostic and prognostic information. The aim of this study was to investigate the alterations of this autonomic regulation in the progress of a normal pregnancy and in several pregnancy disorders associated with hypertension, especially pre-eclampsia, applying the method of Joint Symbolic Dynamics (JSD). The JSD reveals nonlinear interactions/ coupling between two time series.

Blockade of 5-HT2A receptors suppresses hyperthermic but not cardiovascular responses to psychosocial stress in rats.

The aim of this study was to determine whether 5-HT2A receptors mediate cardiovascular and thermogenic responses to acute psychological stresses. For this purpose, adult male Wistar hooded rats instrumented for telemetric recordings of either electrocardiogram (ECG) (n=12) or arterial pressure (n=12) were subjected, on different days, to four 15-min episodes of social defeat. Prior to stress, animals received s.c. injection of the selective 5-HT2A receptor antagonist SR-46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate) (at doses of 0.3, 1.0 and 3.0 mg/kg) or vehicle. The drug had no effect on basal heart rate or heart rate variability indexes, arterial pressure, and core body temperature. Social defeat elicited significant and substantial tachycardic (347+/-7 to 500+/-7 bpm), pressor (77+/-4 to 97+/-4 mm Hg) and hyperthermic (37.0+/-0.3 to 38.5+/-0.1 degrees C) responses. Blockade of 5-HT2A receptors, at all doses of the antagonist, completely prevented stress-induced hyperthermia. In contrast, stress-induced cardiovascular responses were not affected by the blockade (except small reduction of tachycardia by the highest dose of the drug). We conclude that in rats, 5-HT2A receptors mediate stress-induced hyperthermic responses, but are not involved in the genesis of stress-induced rises in heart rate or arterial pressure, and do not participate in cardiovascular control at rest.

The effect of orthostasis on recurrence quantification analysis of heart rate and blood pressure dynamics.

The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.

Acylation stimulating protein is associated with pregnancy weight gain.

Among the proteins secreted by adipocytes, acylation stimulating protein (ASP), which plays a crucial role in energetic balance regulation, merits particular attention. ASP is a protein of the C3 complement system, responsible for glucose and lipids metabolism in an insulin-independent mechanism. ASP's role during pregnancy and its interactions with pregnancy hormones remains unknown. The lipogenic character of ASP may impose a question as to what extent this hormone participates in pregnant women lipogenesis, and what is the basal and postprandial ASP secretion during the second trimester of pregnancy. The results of the examinations of 26 pregnant women during the second trimester of their first pregnancy were analyzed. Due to the limited data available in the literature, a control group was examined. The group consisted of 8 healthy non-pregnant patients within similar age ranges. Blood samples were collected in order to determine ASP, total cholesterol, HDL, LDL and triglyceride levels. Basal ASP levels present in obese pregnant women (group OBP; 30.20 +/- 2.13 ng/mL) were significantly higher than those in the healthy control group (group LnP; 20.49 +/- 1.97 ng/mL), P<0.05. Mann-Whitney U test- analysis of these group differences indicated that OBP patients had significantly higher ASP levels than controls at 30 (P<0.01), 60 (P<0.01), and 120 (P<0.01) min after a meal. After a meal, the incremental ASP area under the curve in group OBW patients was significantly higher from that observed in control group LnP (718,9 +/- 263,9 ng/mL x 2h vs. 35,1 +/- 14,6 ng/mL x 2h, P<0.05). Basal concentration of triglycerides, total cholesterol and LDL cholesterol were significantly higher in all pregnant women compared to the group of non-obese non-pregnant women. It was found that lipid parameters were highly dependent upon body mass gain during pregnancy. Group OBP demonstrated significantly higher basal concentrations of all parameters of lipid metabolism in comparison with the remaining groups of pregnant patients. In conclusion, we found abnormalities of ASP and lipid profiles in lean, overweight, and obese pregnant women strictly connected with obesity. Acylation stimulating protein correlated with lipid parameters, suggesting increased risk of dyslipidemia in obese pregnant women.

Epidemiology of peri/intraventricular haemorrhage in newborns at term.

Peri/intraventricular hemorrhage (PIVH) has significant consequences, particularly leading to cases of adverse neurodevelopment. The aim of this study was to asses the epidemiology of peri/intraventricular haemorrhage in newborns born at term. Study was designed and performed according to epidemiological model of case-controlled studies. The study population was based on 2675 full-term neonates (the mean gestational age was 39.1 +/- 1.2 weeks) admitted to Department of Neonatology of Medical University of Silesia in Katowice (Poland) between the years 2003-2005. Periventricular/intraventricular hemorrhage was diagnosed in 392 neonates (14.65%). In this group of neonates 281 (71.68%) were diagnosed as IVH I degrees , 108 (27.55%) as PIVH II degrees , 2 (0.5%) as PIVH III degrees and in 1 neonate (0.25%) as IVH IV degrees . Further research was carried out on 392 neonates who were diagnosed with PIVH (together I degrees -IV degrees ) and 2283 healthy neonate. The study's inclusion criterion was term delivery (after 37(th) week of gestation). Mean gestational age of the group was 39.11 +/-1.26 weeks and ranged from 37 to 43 weeks. The mean gestational age of neonates with PIVH was 38.91 +/- 1.26 week and -38.14 +/- 1.23 week for those neonates without this pathology. Also, the various potential risk factors of PIVH were analyzed such as: gender, newborn's condition in the 5 minutes after birth (assessed by Apgar score), type of delivery (vaginal, cesarean section, vacuum extractor), umbilical collision, intrauterine infection, hypertension, mother's inflammation of urinary tract and infection of upper airways. We postulate that the etiology of PIVH in term neonates is multifactoral. The findings suggest that male gender, lower birth weight and the mode of delivery are associated with the development of PIVH in term neonates.

Collisions of dark solitons in elongated Bose-Einstein condensates.

We present experimental data showing the head-on collision of dark solitons generated in an elongated Bose-Einstein condensate. No discernable interaction can be recorded, in full agreement with the fundamental theoretical concepts of solitons as mutually transparent quasiparticles. Our soliton generation technique allows for the creation of solitons with different depths; hence, they can be distinguished and their trajectories be followed. Simulations of the 1D-Gross-Pitaevskii equation have been performed to compare the experiment with a mean-field description.

Reduced short-term complexity of heart rate and blood pressure dynamics in patients with diabetes mellitus type 1: multiscale entropy analysis.

Multiscale entropy (MSE) analysis provides information about complexity on various time scales. The aim of this study was to test whether MSE is able to detect autonomic dysregulation in young patients with diabetes mellitus (DM). We analyzed heart rate (HR) oscillations, systolic (SBP) and diastolic blood pressure (DBP) signals in 14 patients with DM type 1 and 14 age- and sex-matched healthy controls. SampEn values (scales 1-10) and linear measures were computed. HR: among the linear measures of heart rate variability significant differences between groups were only found for RMSSD (p = 0.043). MSE was significantly reduced on scales 2 and 3 in DM (p = 0.023 and 0.010, respectively). SBP and DBP: no significant differences were detected with linear measures. In contrast, MSE analysis revealed significantly lower SampEn values in DM on scale 3 (p = 0.039 for SBP; p = 0.015 for DBP). No significant correlations were found between MSE and linear measures. In conclusion, MSE analysis of HR, SBP and DBP oscillations is able to detect subtle abnormalities in cardiovascular control in young patients with DM and is independent of standard linear measures.

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders.

Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.

Joint symbolic dynamic analysis of cardiorespiratory interactions in patients on weaning trials.

Assessing autonomic control provides information about patho-physiological imbalances. Measures of variability of the cardiac interbeat duration RR(n) and the variability of the breath duration TTot(n) are sensitive to those changes. The interactions between RR(n) and TTot(n) are complex and strongly non-linear. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate these interactions in patients on weaning trials. 78 patients from mechanical ventilation are studied: Group A (patients that failed to maintain spontaneous breathing and were reconnected) and Group B (patients with successful trials). Using the concept of joint symbolic dynamics, cardiac and respiratory changes were transformed into a word series, and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in 13 words, and the most significant pn(Wc010, r010): 0.0041 ± 0.0036 (group A) against 0.0012 ± 0.0024 (group B), p-value = 0.00001. The number of seldom occurring word types (forbidden words) also presents significant differences fwcr: 6.9 ± 6.6 against 13.5 ± 5.3, p-value = 0.00004. Joint symbolic dynamics provides an efficient non-linear representation of cardiorespiratory interactions that offers simple physiological interpretations.

Forecasting of life threatening arrhythmias using the compression entropy of heart rate.

OBJECTIVES: Ventricular tachycardia (VT) provoking sudden cardiac death (SCD) are a major cause of mortality in the developed countries. The most efficient therapy for SCD prevention are implantable cardioverter defibrillators (ICD). In this study heart rate variability (HRV) measures were analyzed for short-term forecasting of VT in order to improve VT sensing and to enable a patient warning of forth-coming shocks. METHODS: The last 1000 normal beat-to-beat intervals before 50 VT episodes stored by the ICD were analyzed and compared to individually acquired control time series (CON). HRV analysis was performed with standard parameters of time and frequency domain as suggested by the HRV Task Force and furthermore with a newly developed and optimized nonlinear parameter that assesses the compression entropy of heart rate (Hc). RESULTS: Except of meanNN (p = 0.02) we found no significant differences in standard HRV parameters. In contrast, Hc revealed highly significant (p = 0.007) alterations in VT compared with CON suggesting a decreased complexity before the onset of VT. CONCLUSION: Compression entropy might be a suitable parameter for short-term forecasting of life-threatening tachycardia in ICD.

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

Hypertensive pregnancy disorders are a leading cause of perinatal and maternal morbidity and mortality. Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) are relevant predictors of cardiovascular risk in humans. The aim of the study was to evaluate whether HRV, BPV, and BRS differ between distinct hypertensive pregnancy disorders. Continuous heart rate and blood pressure recordings were performed in 80 healthy pregnant women as controls (CON), 19 with chronic hypertension (CH), 18 with pregnancy-induced hypertension (PIH), and 44 with pre-eclampsia (PE). The data were assessed by time and frequency domain analysis, nonlinear dynamics, and BRS. BPV is markedly altered in all three groups with hypertensive disorders compared to healthy pregnancies, whereby changes were most pronounced in PE patients. Interestingly, this increase in PE patients did not lead to elevated spontaneous baroreflex events, while BPV changes in both the other hypertensive groups were paralleled by alterations in baroreflex parameters. The HRV is unaltered in CH and PE but significantly impaired in PIH. We conclude that parameters of the HRV, BPV, and BRS differ between various hypertensive pregnancy disorders. Thus, distinct clinical manifestations of hypertension in pregnancy have different pathophysiological, regulatory, and compensatory mechanisms.

[Heart rate and blood pressure interaction in normotensive and chronic hypertensive pregnancy]. / Herzfrequenz- und Blutdruckinteraktion bei normotensiver und chronisch hypertensiver Schwangerschaft.

Pregnancy has impact on autonomic control. Since hypertensive pregnancy disorders are a major cause of maternal mortality we investigated the baroreflex sensitivity (BRS) in chronic hypertensive pregnant women (CH), normotensive pregnant (PRE) and non-pregnant (NPRE) women. In addition to the traditional 'sequence method' we used joint symbolic dynamics (JSD). BRS was significantly reduced in all pregnancies compared with NPRE (p < 0.00001) but there was no significant difference between CH and PRE. Contrary, the JSD measures revealed significant differences (p < 0.00001) in the heart rate and blood pressure interactions between PRE and CH. In conclusion, JSD measures uncovered a different gestation related adaptation of autonomic regulation in women with chronic.