Vagal cardiac control in rats with LPS-induced lung injury.

Heart rate variability (HRV) as an index of cardiac autonomic control in acute lung injury (ALI) has been evaluated in anaesthetized rats intratracheally instilled with bacterial lipopolysaccharide (LPS) and ventilated with breathing frequency of 60/min, 40% oxygen, inspiratory time 40%, tidal volume of 6 mL/kg. ECG was recorded before and 30, 60, 120, 180 and 240 min after LPS or saline (control) administration. HRV was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD and spectral power in high frequency (HF) band. Lactate in plasma, and oxidative stress, IL-1ß, IL-5, IL-12p70 and IL-13 and galectin-3 in heart tissue raised in LPS-injured rats. Overall HRV magnitude (SDRR) and marker of vagal heart rate control (RMSSD), as well as frequency domain parameter, spectral power HF was increased 120 and 180 min since ALI onset. In conclusion, LPS-induced ALI is accompanied by altered vagal cardiac control mediated by autonomic nervous system, likely based on the close relationship between immune response and vagally mediated autonomic nervous activity.

CHANGES IN THE VISION OF ADULT AMBLYOPIC PATIENTS FOLLOWING CLEAR LENS EXTRACTION.

AIMS: The aim of the study was to retrospectively evaluate changes in vision after the implantation of trifocal (tIOL) or rotationally asymmetric multifocal artificial intraocular lenses (mIOL) in patients undergoing clear lens extraction. The main goal was to determine whether changes to central visual acuity occur after the implantation of an IOL at a follow-up examination after one year. Other objectives were to determine the difference between the groups with implanted diffractive and rotationally asymmetric artificial intraocular lenses, as well as to evaluate the risk of accurate correction in patients who had lived most of their lives "undercorrected". MATERIAL AND METHODS: In our study, we present a retrospective longitudinal evaluation of results in patients after the implantation of an artificial intraocular lens. In the period from 2013 to 2020, we evaluated changes in the vision of 22 patients aged 39-59 years, of whom 18 were women and 5 were men. The average preoperative refraction of myopic eyes was +5.7 ±2.13 Dsf and +1.24 ±0.86 Dcyl. In amblyopic eyes, 7 diffractive lenses and 15 rotationally asymmetric lenses were used. RESULTS: Uncorrected distance visual acuity before surgery and one year (1Y) after was 0.13 ±0.09 vs. 0.57 ±0.28 (p < 0.001); the best corrected distance visual acuity before and 1Y after was 0.53 ±0.22 vs. 0.62 ±0.29 (p = 0.024); uncorrected near visual acuity before and 1Y after was 0.06 ±0.06 vs. 0.48 ±0.32 (p < 0.001); the best corrected near visual acuity before and afér the surgical procedure was 0.45 ±0.27vs. 0.55 ±0.35 (p = 0.014). CONCLUSION: Implantation of tIOL and mIOL lenses was effective in our group of patients with amblyopia, thus improving uncorrected distance and near visual acuity and without serious adverse effects. At the same time, we evaluate that the change in refraction and the removal of anisometropia lead to a significant change in the best corrected visual acuity for distance or near vision at the one-year follow-up examination.

Mechanisms of Cardiovascular Changes of Phototherapy in Newborns with Hyperbilirubinemia.

During phototherapy of jaundiced newborns, vasodilation occurs in the skin circulation compensated by vasoconstriction in the renal and mesenteric circulation. Furthermore, there is a slight decrease in cardiac systolic volume, and blood pressure, as well as an increase in heart rate and discrete changes in the heart rate variability (HRV). The primary change during phototherapy is the skin vasodilation mediated by multiple mechanisms: 1) Passive vasodilation induced by direct skin heating effect of the body surface and subcutaneous blood vessels, modified by myogenic autoregulation. 2) Active vasodilation mediated via the mechanism provided by axon reflexes through nerve C-fibers and humoral mechanism via nitric oxide (NO) and endothelin 1 (ET-1). During and after phototherapy is a rise in the NO:ET-1 ratio. 3) Regulation of the skin circulation through the sympathetic nerves is unique, but their role in skin vasodilation during phototherapy was not studied. 4) Special mechanism is a photorelaxation independent of the skin heating. Melanopsin (opsin 4) - is thought to play a major role in systemic vascular photorelaxation. Signalling cascade of the photorelaxation is specific, independent of endothelium and NO. The increased skin blood flow during phototherapy is enabled by the restriction of blood flow in the renal and mesenteric circulation. An increase in heart rate indicates activation of the sympathetic system as is seen in the measures of the HRV. High-pressure, as well as low-pressure baroreflexes, may play important role in these adaptation responses. The integrated complex and specific mechanism responsible for the hemodynamic changes during phototherapy confirm adequate and functioning regulation of the neonatal cardiovascular system, including baroreflexes.

Autonomic control of heart and vessels in patients with very early stage of Parkinson disease.

Objective. Non-motor symptoms including those reflecting autonomic cardiovascular dysregulation are often present in Parkinson disease. It is unclear whether it is possible to detect cardiovascular autonomic dysregulation in the very early stage of Parkinson disease potentially supporting the concept of the upstream propagation of nervous system damage through autonomic nerves. We hypothesized that cardiovascular dysregulation should precede the motor symptoms and at the time of their occurrence autonomic dysregulation should be clearly demonstrable. Therefore, the aim of this study was to assess the various aspects of autonomic cardiovascular control in the very early stage of Parkinson disease.Approach. We performed prospective case-control study on 19 patients with Parkinson disease (<6 months after motor signs occurrence) and 19 healthy control subjects. For each phase of study protocol (supine, head-up tilt, supine recovery), we calculated a wide array of cardiovascular control related parameters reflecting cardiac chronotropic, cardiac inotropic and vasomotor control and baroreflex mediated cardiovascular response.Main results. We observed the well-preserved heart rate and blood pressure control in patients with early stage of Parkinson disease. However, causal analysis of interactions between heart rate and blood pressure oscillations revealed subtle differences in baroreflex function and baroreflex mediated vasoconstriction response to orthostasis. Furthermore, a tendency towards a decreased contraction strength in Parkinson disease was observed.Significance. Considering only subtle cardiovascular control impairment in our study employing a wide array of sensitive methods at the time when motor signs were clearly expressed, we suggest that motor signs dominated in this stage of Parkinson disease.

Stroke volume variation as an index of fluid responsiveness can be impaired by mental stress.

Cardiac stroke volume variation (SVV) measurement is one of the techniques to detect fluid-responsive hypovolemia in patients under mechanical ventilation. There is an ongoing effort to apply SVV for this purpose also in conscious patients. However, the effect of mental stress often occurring in conscious patients as a potential confounding factor on SVV is not known. The aim of our study was to compare effect of simulated hypovolemia and mental stress on SVV in healthy volunteers in the context of potential confounders - breathing pattern, respiratory sinus arrhythmia magnitude and sex. We examined 102 young healthy volunteers (58 females), mean age 18.6 years. Finger arterial blood pressure was recorded by volume-clamp photoplethysmographic method (Finometer Pro, FMS, Amsterdam, Netherland). From the blood pressure curve, a built in ModelFlow algorithm calculated stroke volume values (SV) for each heartbeat. Respiratory volume was recorded using calibrated respiratory inductive plethysmography (RespiTrace, NIMS, Miami Beach, FL, USA). During four phases of examination protocol (supine rest, head-up tilt (HUT), supine recovery, mental arithmetic task (MA)) we analyzed SVV related to respiratory activity. While during HUT we found an expected increase in SVV together with mean SV decrease, SVV significantly decreased during MA. The observed changes during MA could be attributed to an increased respiratory rate and/or decreased respiratory sinus arrhythmia. Sex related differences in SVV responses to HUT and MA were observed. We conclude that mental stress together with respiratory sinus arrhythmia and respiratory pattern changes can significantly influence SVV as a potential index of fluid responsiveness in conscious patients.

EVALUATION OF THE CORNEAL STROMAL DEMARCATION LINE AFTER THE ACCELERATED CORNEAL CROSS-LINKING USING ANTERIOR SEGMENT OCT.

OBJECTIVES: Evaluation of the visibility and depth of the demarcation line in the corneal stroma in eyes with keratoconus 1 month and 3 months after epi-off accelerated corneal cross-linking (ACXL) using anterior segment optical coherence tomography (AS OCT). MATERIAL AND METHODS: This study analyses a group of 34 eyes with keratoconus 1 month and 3 months after ACXL (9 mW/cm2 for 10 min). The group was classified based on the ABCD clinical classification of keratoconus according to Belin and Duncan. AS OCT (ZeissCirrus 500, Anterior Segment Premier module) was used to assess the visibility and exact depth of the demarcation line in the corneal stroma. RESULTS: The demarcation line was visible 1 month after ACXL in 76.5% of eyes with a mean depth of 238.13 ±20.36 μm and 3 months after ACXL in 100% of eyes with a mean depth of 263.43 ±12.59 μm. Statistical analysis of the group did not show a significant relationship between the disease stage and the demarcation line visibility; however, there was a trend towards higher age (>30 years) in the group in those eyes where the demarcation line was visible vs. partially visible 3 months after ACXL. We found no difference in the mean and maximum line depth when comparing 1 month and 3 months after the procedure. There were no cases of disease progression 3 months after ACXL in the group. CONCLUSION: Our study suggests that the assessment of the demarcation line in the corneal stroma is more reliable 3 months compared to 1 month after ACXL. We also observed a trend towards higher patient age in eyes where the demarcation line was clearly visible 3 months after ACXL. We did not confirm a relationship between the stage of keratoconus and the depth of the line, nor a difference in its mean and maximum depth 1 month and 3 months after the procedure.

Input for baroreflex analysis: which blood pressure signal should be used?

The baroreflex (BR) is an important physiological regulatory mechanism which reacts to blood pressure perturbations with reflex changes of target variables such as the heart period (electrocardiogram derived RR interval) or the peripheral vascular resistance (PVR). Evaluation of cardiac chronotropic (RR as a target variable) and vascular resistance (target PVR) BR arms was in previous studies mainly based on the use of the spontaneous variability of the systolic or diastolic blood pressure (SBP, DBP), respectively, as the input signals. The use of other blood pressure measures such as the mean blood pressure (MBP) as an input signal for BR analysis is still under investigation. Making the assumption that the strength of coupling along the BR indicates the more appropriate input signal for baroreflex analysis, we employ partial spectral decomposition to assess in the frequency domain the causal coupling from SBP, MBP or DBP to RR or PVR. Noninvasive beat-to-beat recording of RR, SBP, MBP and DBP and PVR was performed in 39 and 36 volunteers in whom orthostatic and cognitive loads were evoked respectively through head-up tilt and mental arithmetic task. At rest, the MBP was most tightly coupled with RR, in contrast to the analysis of the vascular resistance BR arm where the results showed similar importance of all blood pressure input signals. During orthostasis, the increased importance of SBP as the input signal for BR analysis along the cardiac chronotropic arm was demonstrated. In addition, the gain from MBP to RR was more sensitive to physiological state changes compared to gains with SBP or DBP signal as inputs. We conclude that the coupling strength depends not only on the analysed baroreflex arm but also on the selection of the input blood pressure signal and the physiological state. The MBP signal should be more frequently used for the cardiac baroreflex analysis.

Arterial compliance and its dynamics in obese adolescents.

Arterial compliance (AC) decrease with aging is accelerated by factors associated with the progression of atherosclerotic process, including obesity. Prevalence of obesity increases not only in adult population but also in children and adolescents. The results of studies characterizing the effect of obesity on AC (often indirectly estimated by pulse wave velocity (PWV)) are contradictory. Considering the limitations of previously applied methods and the need to interpret AC values in the context of potential confounders or during various physiological states, the aim of this study was to compare AC of control and obese adolescents during four different physiological states: supine rest, head-up tilt (HUT), supine recovery and mental arithmetic (MA). AC was assessed by the method based on two-element Windkessel model as the ratio of a time constant t characterizing diastolic blood pressure decay and total peripheral resistance (TPR). In total, fifty healthy and normotensive subjects (40 females, 10 males, age 17.5 years (SD=1.1 years)) were examined - 25 obese and 25 age- and sex-matched control subjects. We observed significantly increased AC values during all phases in obese group. An increase in AC was also preserved after controlling for blood pressure influence. These results were confirmed using PWV based AC estimation. Interestingly, AC decreased similarly during stress phases (HUT, MA) in both groups. Lastly, TPR was decreased throughout the study protocol in obese subjects. In conclusion, AC is increased in young obese subjects consistently during various physiological states. Furthermore, changes of physiological states evoke similar response of AC in both groups indicating preserved autonomic control of elastic arteries. A decreased TPR in obese subjects points towards the influence of different maturation state of the arterial tree and/or changes in vasomotion possibly counterbalancing acceleration of atherosclerosis process.

USE OF A FEMTOSECOND LASER IN CATARACT SURGERY.

AIMS: Cataracts continue to be the leading cause of blindness worldwide. Phacoemulsification is the gold standard in the treatment of cataracts. The aim of the study was to compare the postoperative results of the phacoemulsification technique in comparison with femtosecond laser-assisted cataract surgery (FLACS). MATERIAL AND METHODS: Our work retrospectively evaluates the results of patients after implantation of an artificial intraocular lens for cataract from May 2017 to March 2019. The study evaluated a total of 80 implanted lenses in 47 patients operated on by two surgeons. Of the 47 patients, 28 were women. The mean age in the group at the time of surgery was 63.7 years, ranging from 34-79 years. Patients could choose FLACS (n = 45) surgery or standard phacoemulsification procedure (n = 35). RESULTS: Upon a comparison of the group regarding uncorrected distal visual acuity (UCDVA) up to 12 months after surgery, the group FAKO CATARACTS recorded 0.85 ±0.18 vs. 0.93 ±0.12 in the FEMTO CATARACTS group (p = 0.021), comparably uncorrected near visual acuity (UCNVA) was 0.77 ±0.18 vs. 0.84 ±0.17 (p = 0.034) respectively. A difference in the use of phacoemulsification energy (OZIL) was measured in patients with phacoemulsification 3.5 ±3.1 and in the use of femtosecond laser 2.2 ±3.1, (p = 0.005). In all cases, an AT LISA 839 trifocal lens (Carl Zeiss Meditec, Germany) was implanted. CONCLUSION: The femtosecond platform assists the surgeon in cataract surgery with capsulorhexis and pre-fragmentation of the lens nucleus, which can be advantageous especially for complicated cataracts. We recorded significantly higher uncorrected distance and near visual acuity in the FLACS group, and also a significantly lower value of the phacoemulsification energy used.

Cardiovascular changes during phototherapy in newborns.

Phototherapy is the most effective non-invasive method of neonatal hyperbilirubinemia treatment. Application of this method can be associated with side effects including changes in the cardiovascular system. During phototherapy, the primary effects in the cardiovascular system include cutaneous vasodilation leading to skin hyperperfusion and subsequent redistribution of blood. The increased blood flow through the skin is associated with increased transepidermal water loss. Further effects include an increase in cerebral blood flow. Redistribution of blood to the cutaneous bed is compensated by hypoperfusion in the splanchnic area (mostly postprandial) and a significant reduction of the renal blood flow. Regarding closure/reopening of the ductus arteriosus, the results suggest that that phototherapy does not affect ductal patency. During phototherapy the cardiac output can be slightly reduced due to a decreased stroke volume, especially in preterm newborns. Systemic blood pressure is decreased and heart rate is elevated in both preterm and term newborns during phototherapy. The heart rate variability is slightly reduced. Symbolic dynamics analysis of the short-term HRV showed that during phototherapy the activity of the ANS regulating the heart rate is shifted towards the dominancy of the sympathetic activity. The responses in the cardiovascular system of premature/mature newborns without other pathology confirm a well physiologically functioning control of this system, even under specific conditions of phototherapy.

Extending the spectral decomposition of Granger causality to include instantaneous influences: application to the control mechanisms of heart rate variability.

Assessing Granger causality (GC) intended as the influence, in terms of reduction of variance of surprise, that a driver variable exerts on a given target, requires a suitable treatment of 'instantaneous' effects, i.e. influences due to interactions whose time scale is much faster than the time resolution of the measurements, due to unobserved confounders or insufficient sampling rate that cannot be increased because the mechanism of generation of the variable is inherently slow (e.g. the heartbeat). We exploit a recently proposed framework for the estimation of causal influences in the spectral domain and include instantaneous interactions in the modelling, thus obtaining (i) a novel index of undirected instantaneous causality and (ii) a novel measure of GC including instantaneous effects. An effective procedure to speed up the optimization of parameters in this frame is also presented. After illustrating the proposed formalism in a theoretical example, we apply it to two datasets of cardiovascular and respiratory time series and compare the values obtained within the frequency bands of physiological interest by the proposed total measure of causality with those derived from the standard GC analysis. We find that the inclusion of instantaneous causality allows us to correctly disentangle the baroreflex mechanism from the effects related to cardiorespiratory interactions. Moreover, studying how controlling the respiratory rhythm acts on cardiovascular interactions, we document an increase of the direct (non-baroreflex mediated) influence of respiration on the heart rate in the respiratory frequency band when switching from spontaneous to paced breathing. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Beta-adrenergic receptors gene polymorphisms are associated with cardiac contractility and blood pressure variability.

Beta-adrenergic receptors (beta-ARs) play a pivotal role in the cardiovascular regulation. In the human heart beta1- and beta2-ARs dominate in atria as well as in ventricle influencing heart rate and myocardial contractility. Some single nucleotide polymorphisms (SNPs) of beta-ARs might influence cardiovascular function. However, the influence of beta-AR genes SNPs on hemodynamic parameters at rest and their reactivity under stress is still not well known. We aimed to explore the associations between four selected beta-ARs gene polymorphisms and selected cardiovascular measures in eighty-seven young healthy subjects. While in beta1-AR polymorphism rs1801252 no significant association was observed, second beta1-AR polymorphism rs1801253 was associated with decreased cardiac output and cardiac index during all phases and with decreased flow time corrected and ejection time index at rest and during mental arithmetics. Polymorphism rs1042713 in beta2-AR was associated with alterations in blood pressure variability at rest and during head-up-tilt, while rs1042714 was associated predominantly with decreased parameters of cardiac contractility at rest and during mental arithmetics. We conclude that complex analysis of various cardiovascular characteristics related to the strength of cardiac contraction and blood pressure variability can reveal subtle differences in cardiovascular sympathetic nervous control associated with beta-ARs polymorphisms.

Short-term arterial compliance changes in the context of systolic blood pressure influence.

Arterial compliance (C) is a complex parameter influencing ventricular-arterial coupling depending on structural (arterial wall remodeling) and functional (blood pressure, smooth muscles tone) changes. Based on Windkessel model, C can be calculated as the ratio of a time constant Tau characterizing diastolic blood pressure decay and total peripheral resistance (TPR). The aim of this study was to assess changes of C in the context of systolic arterial pressure (SAP) perturbations during four physiological states (supine rest, head-up tilt, supine recovery, mental arithmetic). In order to compare pressure independent changes of C a new index of C120 was proposed predicting C value at 120 mm Hg of SAP. Eighty-one healthy young subjects (48 f, average age 18.6 years) were examined. Hemodynamic parameters were measured beat-to-beat using volume-clamp photoplethysmographic method and impedance cardiography. We observed that C was strongly related to SAP values on the beat-to-beat time scale. Interestingly, C120 decreased significantly during stress phases. In conclusion, potential changes of SAP should be considered when measuring C. Arterial compliance changes in the opposite direction to TPR pointing towards influence of vascular tone changes on its value.

Baroreflex sensitivity and blood pressure in premature infants - dependence on gestational age, postnatal age and sex.

To characterize the differences in baroreflex sensitivity (BRS), blood pressure (BP), heart rate (HR) and respiration rate (RR) in preterm infants with a similar postconceptional age reached by various combinations of gestational and postnatal ages. To detect potential sex differences in assessed cardiovascular parameters. The study included 49 children (24 boys and 25 girls), postconceptional age 34.6+/-1.9 weeks. Two subgroups of infants were selected with the similar postconceptional age (PcA) and current weight, but differing in gestational (GA) and postnatal (PnA) ages, as well as two matched subgroups of boys and girls. Blood pressure (BP) was recorded continuously using Portapres device (FMS). A stationary segment of 250 beat-to-beat BP values was analyzed for each child. Baroreflex sensitivity (BRS) was calculated by cross-correlation sequence method. Despite the same PcA age and current weight, children with longer GA had higher BRS, diastolic and mean BP than children with shorter GA and longer PnA age. Postconceptional age in preterm infants is a parameter of maturation better predicting baroreflex sensitivity and blood pressure values compared to postnatal age. Sex related differences in BRS, BP, HR and RR were not found in our group of preterm infants.

Noninvasive arterial compliance estimation.

Arterial compliance is an important cardiovascular parameter characterizing mechanical and structural properties of arteries and significantly influencing ventricular-arterial coupling. Decreased arterial compliance is associated with several physiological states and pathological processes. Furthermore, arterial compliance is influenced by other cardiovascular parameters even at short time scales. Today, there are numerous noninvasive methods of estimation arterial compliance in vivo introducing some level of confusion about selection of the best method for particular application and measurement setting. In this review, the most common noninvasive methods of arterial compliance estimation are summarized, discussed and categorized. Finally, interpretation of estimated arterial compliance in the context of other possible confounders is discussed.

Adrenergic receptors gene polymorphisms and autonomic nervous control of heart and vascular tone.

Adrenergic receptors (ARs) are the primary targets of catecholamines released from the sympathetic nerve endings during their activation. ARs play a central role in autonomic nervous system and serve as important targets of widely used drugs. Several ARs gene polymorphisms were found to be associated with cardiovascular disease in previous clinical studies. Although more precise mechanism of the polymorphisms influence on autonomic control of cardiovascular system was studied in many previous physiological studies, their results are not unequivocal. This paper reviews the results of clinical and physiological studies focused on the impact of selected common single nucleotide polymorphisms of ARs genes involved in sympathetic control on cardiovascular system and its control. In summary, many studies assessed only a very limited range of cardiovascular control related parameters providing only very limited view on the complex cardiovascular control. The overview of partially contradicting results underlines a need to examine wider range of cardiovascular measures including their reactivity under various stress conditions requiring further study. It is expected that an effect of one given polymorphism is not very prominent, but it is suggested that even subtle differences in cardiovascular control could - on a longer time scale - lead to the development of severe pathological consequences.

Vascular resistance arm of the baroreflex: methodology and comparison with the cardiac chronotropic arm.

Baroreflex response consists of cardiac chronotropic (effect on heart rate), cardiac inotropic (on contractility), venous (on venous return) and vascular (on vascular resistance) arms. Because of the simplicity of its measurement, the cardiac chronotropic arm is most often analyzed. The aim was to introduce a method to assess the vascular baroreflex arm and to characterize its changes during stress. We evaluated the effect of orthostasis and mental arithmetics (MA) in 39 (22 women, 17 men; median age: 18.7 yr) and 36 (21 women, 15 men; 19.2 yr) healthy volunteers, respectively. We recorded systolic (SBP) and mean (MBP) blood pressure by volume-clamp method and R-R interval (RR) by ECG. Cardiac output (CO) was recorded by impedance cardiography. From MBP and CO, peripheral vascular resistance (PVR) was calculated. The directional spectral coupling and gain of cardiac chronotropic (SBP to RR) and vascular (SBP to PVR) arms were quantified. The strength of the causal coupling from SBP to PVR was significantly higher than that of SBP to RR coupling over the whole protocol (P < 0.001). Along both arms, the coupling was higher during orthostasis compared with the supine position (P < 0.001 and P = 0.006); no MA effect was observed. No significant changes in the spectral gain (ratio of RR or PVR change to a unit SBP change) across all phases were found (0.111 ≤ P ≤ 0.907). We conclude that changes in PVR are tightly coupled with SBP oscillations via the baroreflex, providing an approach for baroreflex vascular arm analysis with the potential to reveal new aspects of blood pressure dysregulation.NEW & NOTEWORTHY Baroreflex response consists of several arms, but the cardiac chronotropic arm (blood pressure changes evoking heart rate response) is usually analyzed. This study introduces a method to assess the vascular baroreflex arm with the continuous noninvasive measurement of peripheral vascular resistance as an output considering causality in the interaction between oscillations and slower dynamics of vascular tone changes. We conclude that although vascular baroreflex arm involvement becomes dominant during orthostasis, gain of this interaction is relatively stable.

Quantification of Different Regulatory Pathways Contributing to Heartbeat Dynamics during Multiple Stimuli: a Proof of the Concept.

The dynamical interplay between brain and heart is mediated by several feedback mechanisms including the central autonomic network and baroreflex loop at a peripheral level, also for a short-term regulation. State of the art focused on the characterization of each regulatory pathway through a single stressor elicitation. However, no studies targeted the actual quantification of different mediating routes leading to the generation of heartbeat dynamics, particularly in case of combined exogenous stimuli. In this study, we propose a new approach based on computational modeling to quantify the contribution of multiple concurrent stimuli in modulating cardiovascular dynamics. In this preliminary attempt, the model estimates the high-frequency power of heartbeat dynamics, and derives disentangling coefficients quantifying the effect of multiple elicitations. Model evaluation is performed on healthy rate variability (HRV) series from fourteen healthy subjects undergoing physical (tilt-table) and mental stressors (aritmetics), as well as their combined administration. Results indicate that, at a group-wise level, in base of concurrent physical and mental elicitations, the physical stressor contributes for the 85% of the resulting heartbeat dynamics. These findings are in agreement with the current knowledge on heartbeat regulatory systems, providing valuable perspectives on the quantification of underlying generative mechanisms of HRV.

Information domain analysis of respiratory sinus arrhythmia mechanisms.

Ventilation related heart rate oscillations - respiratory sinus arrhythmia (RSA) - originate in human from several mechanisms. Two most important of them - the central mechanism (direct communication between respiratory and cardiomotor centers), and the peripheral mechanism (ventilation-associated blood pressure changes transferred to heart rate via baroreflex) have been described in previous studies. The major aim of this study was to compare the importance of these mechanisms in the generation of RSA non-invasively during various states by quantifying the strength of the directed interactions between heart rate, systolic blood pressure and respiratory volume signals. Seventy-eight healthy volunteers (32 male, age range: 16.02-25.77 years, median age: 18.57 years) participated in this study. The strength of mutual interconnections among the spontaneous beat-to-beat oscillations of systolic blood pressure (SBP), R-R interval (RR signal) and respiration (volume changes - RESP signal) was quantified during supine rest, orthostatic challenge (head-up tilt, HUT) and cognitive load (mental arithmetics, MA) using bivariate and trivariate measures of cardio-respiratory information transfer to separate baroreflex and nonbaroreflex (central) mechanisms. Our results indicate that both basic mechanisms take part in RSA generation in the intact cardiorespiratory control of human subjects. During orthostatic and mental challenges baroreflex based peripheral mechanism becomes more important.

Univariate and multivariate conditional entropy measures for the characterization of short-term cardiovascular complexity under physiological stress.

OBJECTIVE: A defining feature of physiological systems under the neuroautonomic regulation is their dynamical complexity. The most common approach to assess physiological complexity from short-term recordings, i.e. to compute the rate of entropy generation of an individual system by means of measures of conditional entropy (CE), does not consider that complexity may change when the investigated system is part of a network of physiological interactions. This study aims at extending the concept of short-term complexity towards the perspective of network physiology, defining multivariate CE measures whereby multiple physiological processes are accounted for in the computation of entropy rates. APPROACH: Univariate and multivariate CE measures are computed using state-of-the-art methods for entropy estimation and applied to time series of heart period (H), systolic (S) and diastolic (D) arterial pressure, and respiration (R) variability measured in healthy subjects monitored in a resting state and during conditions of postural and mental stress. MAIN RESULTS: Compared with the traditional univariate metric of short-term complexity, multivariate measures provide additional information with plausible physiological interpretation, such as (i) the dampening of respiratory sinus arrhythmia and activation of the baroreflex control during postural stress; (ii) the increased complexity of heart period and blood pressure variability during mental stress, reflecting the effect of respiratory influences and upper cortical centers; (iii) the strong influence of D on S, mediated by left ventricular ejection fraction and vascular properties; (iv) the role of H in reducing the complexity of D, related to cardiac run-off effects; and (v) the unidirectional role of R in influencing cardiovascular variability. SIGNIFICANCE: Our results document the importance of employing a network perspective in the evaluation of the short-term complexity of cardiovascular and respiratory dynamics across different physiological states.