Andrea Calkovska

The effect of orthostatic stress on multiscale entropy of heart rate and blood pressure

Cardiovascular control acts over multiple time scales, which introduces a significant amount of complexity to heart rate and blood pressure time series. Multiscale entropy (MSE) analysis has been developed to quantify the complexity of a time series over multiple time scales. In previous studies, MSE analyses identified impaired cardiovascular control and increased cardiovascular risk in various pathological conditions. Despite the increasing acceptance of the MSE technique in clinical research, information underpinning the involvement of the autonomic nervous system in the MSE of heart rate and blood pressure is lacking. The objective of this study is to investigate the effect of orthostatic challenge on the MSE of heart rate and blood pressure variability (HRV, BPV) and the correlation between MSE (complexity measures) and traditional linear (time and frequency domain) measures. MSE analysis of HRV and BPV was performed in 28 healthy young subjects on 1000 consecutive heart beats in the supine and standing positions. Sample entropy values were assessed on scales of 1-10. We found that MSE of heart rate and blood pressure signals is sensitive to changes in autonomic balance caused by postural change from the supine to the standing position. The effect of orthostatic challenge on heart rate and blood pressure complexity depended on the time scale under investigation. Entropy values did not correlate with the mean values of heart rate and blood pressure and showed only weak correlations with linear HRV and BPV measures. In conclusion, the MSE analysis of heart rate and blood pressure provides a sensitive tool to detect changes in autonomic balance as induced by postural change.

Heart rate variability in young patients with diabetes mellitus and healthy subjects explored by Poincaré and sequence plots

Autonomic neuropathy is a common complication of the diabetes mellitus (DM). The significance of its early diagnosis is very high because the mortality of the patients with this complication is elevated. Considering the effort to apply new mathematical methods to cardiac dysregulation diagnosis, the major aim of the study was to ascertain which of the new heart rate variability (HRV) parameters are different in young patients with DM type 1 compared with control group. The next aim was to assess the HRV changes during prolonged (40 min) supine rest. The heart rate was continuously recorded during supine rest in 17 young patients with DM type 1 (10 women, 7 men) aged 22·4 ± 1·0 years (mean ± SEM). The control group consisted of 17 healthy matched probands. The HRV (time/frequency domains, Poincaré and sequence plots, sample entropy) was analysed in two intervals – T1 starting at fifth minute and T2 starting at 30th minute of supine rest. The major results of our study are: the reduced Poincaré plot pattern measures in the young DM group; the lower percentage of points in the third quadrant of sequence plot (this parameter was not correlated with the mean heart rate) and significant changes in HRV during supine rest in DM group (in contrast to control subjects). In conclusion, HRV parameters based on nonlinear dynamics were able to distinguish cardiac dysregulation in young patients with DM from the control group. The percentage of points in the third quadrant of sequence plot provides information that is not dependent on mean heart rate. Poincaré and sequence plots, together with the rate of HRV changes during supine rest, can provide clinically relevant information usable in diagnosis of the cardiac dysregulation.

Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A

Surfactant protein A (SP-A), a major protein component of natural pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. We investigated the physical and physiological properties of one of these modified natural surfactants (Curosurf) after enrichment with 5% SP-A (SP-A-Curosurf). A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects. In the presence of various potential inhibitors (meconium 5 mg.mL-1, fibrinogen 5 mg.mL-1, albumin 25 mg.mL-1, or whole serum proteins 25 mg.mL-1), Curosurf at a concentration of 5 mg.mL-1 was inactivated while SP-A-Curosurf and natural porcine surfactant at the same concentration had normal maximum and minimum surface tension. This protective effect of SP-A was calcium dependent. In immature newborn rabbits, the improvement of lung-thorax compliance observed after treatment with 100 mg.kg-1 of SP-A-Curosurf was equivalent to that obtained with 200 mg.kg-1 of Curosurf. Similarly, in near-term newborn rabbits with respiratory failure induced by instillation of fibrinogen via the airways, the increase in compliance after administration of 100 mg.kg-1 of SP-A-Curosurf corresponded to that seen after treatment with 200 mg.kg-1 of Curosurf, whereas Curosurf at a dose of 100 mg.kg-1 had no substantial effect. Our data thus indicate that surfactant protein A increases the resistance of Curosurf to inactivation under in vivo conditions.

Complexity and time asymmetry of heart rate variability are altered in acute mental stress.

We aimed to study the complexity and time asymmetry of short-term heart rate variability (HRV) as an index of complex neurocardiac control in response to stress using symbolic dynamics and time irreversibility methods. ECG was recorded at rest and during and after two stressors (Stroop, arithmetic test) in 70 healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%), and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV magnitude was quantified by linear parameters: spectral powers in low (LF) and high frequency (HF) bands. Our results showed a reduction of HRV complexity in stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern classification analysis revealed significantly higher 0V% and lower 2LV% with both stressors, indicating a shift in sympathovagal balance, and significantly higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time irreversibility: significantly lower G% and E with both stressors, P% index significantly declined only with arithmetic test. Linear HRV analysis confirmed vagal withdrawal (lower HF) with both stressors; LF significantly increased with Stroop and decreased with arithmetic test. Correlation analysis revealed no significant associations between symbolic dynamics and time irreversibility. Concluding, symbolic dynamics and time irreversibility could provide independent information related to alterations of neurocardiac control integrity in stress-related disease.

Respiratory sinus arrhythmia is reduced in adolescent major depressive disorder

ObjectiveAlthough the emotion regulatory difficulties in patients with major depressive disorder (MDD) are predicted to associate with impaired cardiovascular autonomic regulation, the changes of cardiac vagal regulation in MDD are incompletely understood. The aim of the study was to evaluate the respiratory sinus arrhythmia (as an index of cardiac vagal regulation) using the spectral analysis in high frequency band of the heart rate variability and the indices of deep breathing test in adolescent patients with major depressive disorder.Materials and methodsTwenty-eight adolescent girls were examined - 14 patients with major depressive disorder without pharmacological treatment (average age: 16.4 ± 0.2 yr) and 14 healthy probands (control group) matched for age and gender. The respiratory sinus arrhythmia was evaluated using the spectral analysis in high frequency band of the heart rate variability (HF-HRV) and the parameters of deep breathing test (I-E, I/E). In addition, mean R-R interval was calculated.ResultsThe adolescent patients with MDD had significantly reduced spectral activity in the HF-HRV and lower I/E, I-E parameters compared to matched healthy subjects (P < 0.05).ConclusionsWe conclude that the adolescent girls with MDD have reduced respiratory sinus arrhythmia indicating cardiac vagal dysregulation. Since impaired cardiac vagal regulation is associated with increased risk of cardiovascular morbidity, this finding underscores the importance of impaired autonomic neurocardiac integrity already in adolescents with major depressive disorder without pharmacological treatment.

Biophysical and Physiological Properties of Porcine Surfactant Enriched with Polymyxin B

Objective: We examined whether the biophysical and physiological properties of Curosurf® were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). Methods: Curosurf was diluted to 1–5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (γmin) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. Results: At surfactant concentration 2 mg/ml, γmin was high (17 ± 8.9 mN/m) but remained low (2.7 ± 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. Conclusion: Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.

New Generation Synthetic Surfactants

The treatment of preterm newborn rabbits with synthetic surfactants containing simple phospholipid mixtures and peptides gives similar tidal volumes to treatment with poractant alfa (Curosurf®). The addition of both surfactant protein B and C analogs to the phospholipid mixture will stabilize the alveoli, measured as lung gas volumes at end expiration, even if no positive end-expiratory pressure is applied. The effect on lung gas volumes seems to depend on the structure of the peptides as well as the phospholipid composition. It seems that synthetic surfactants containing two peptides and a more complex phospholipid composition will be able to replace natural surfactants within the near future, but more experiments need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants.

Combined effects of high-frequency ventilation and surfactant treatment in experimental meconium aspiration syndrome.

Background: Deterioration of lung function in meconium aspiration syndrome may in part be due to inactivation of endogenous surfactant. We evaluated the efficacy of high‐frequency ventilation (HFV) and the combination of HFV and surfactant therapy in the management of respiratory failure induced by experimental meconium aspiration in adult rats.

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-Portas, Guziks and Ehlers 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.

Defensive reflexes of the respiratory system in anaesthetized rabbits during high frequency jet ventilation

The defensive airway reflexes during high frequency jet ventilation (HFJV) were studied in anaesthetized, non‐vagotomized (n = 16) and vagotomized (n = 11) rabbits. The animals were ventilated by a high frequency jet ventilator. Sneezing and coughing were evoked by mechanical stimulation of the airways. During HFJV spontaneous breathing was inhibited only in the non‐vagotomized rabbits. Mechanical stimulation of the airways during HFJV evoked sneezing and coughing, in which the inspiratory component was inhibited. This inhibition occurred not only in defensive reflexes evoked from the regions with increased pressure (trachea, bronchi), but also from the nose. Vagotomy diminished but did not fully eliminate the changes in sneezing accompanying HFJV. The intensity of maximum expiratory efforts was not significantly affected by HFJV in both subgroups.