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Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test.

ABSTRACT: A mathematical model is proposed for the autonomic control of cardiovascular system, which takes into account two separated self-exciting sympathetic control loops of heart rate and peripheral vascular tone. The control loops are represented by self-exciting time-delay systems and their tone depends on activity of the aortic, carotid, and lower-body baroreceptors. The model is used to study the dynamics of the adaptive processes that manifest in a healthy cardiovascular system during the passive head-up tilt test. Computer simulation provides continuous observation of the dynamics of the indexes and variables that cannot be measured in the direct experiment, including the noradrenaline concentration in vessel wall and heart muscle, tone of the sympathetic and parasympathetic control, peripheral vascular resistance, and blood pressure. In the supine and upright positions, we estimated the spectral characteristics of the model variables, especially in the low-frequency band, and the original index of total percent of phase synchronization between the low-frequency oscillations in heart rate and blood pressure signals. The model demonstrates good quantitative agreement with the dynamics of the experimentally observed indexes of cardiovascular system that were averaged for 50 healthy subjects.

SUBMITTER: Ishbulatov YM

PROVIDER: S-EPMC7536219 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test.

Ishbulatov Yurii M YM Karavaev Anatoly S AS Kiselev Anton R AR Simonyan Margarita A MA Prokhorov Mikhail D MD Ponomarenko Vladimir I VI Mironov Sergey A SA Gridnev Vladimir I VI Bezruchko Boris P BP Shvartz Vladimir A VA

Scientific reports 20201005 1

A mathematical model is proposed for the autonomic control of cardiovascular system, which takes into account two separated self-exciting sympathetic control loops of heart rate and peripheral vascular tone. The control loops are represented by self-exciting time-delay systems and their tone depends on activity of the aortic, carotid, and lower-body baroreceptors. The model is used to study the dynamics of the adaptive processes that manifest in a healthy cardiovascular system during the passive ...[more]

PMID: 33020530

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Project description:In sickle cell disease (SCD), prolonged capillary transit times, resulting from reduced peripheral blood flow, increase the likelihood of rigid red cells entrapment in the microvasculature, predisposing to vaso-occlusive crisis. Since changes in peripheral flow are mediated by the autonomic nervous system (ANS), we tested the hypothesis that the cardiac and peripheral vascular responses to head-up tilt (HUT) are abnormal in SCD. Heart rate, respiration, non-invasive continuous blood pressure and finger photoplethysmogram (PPG) were monitored before, during, and after HUT in SCD, anemic controls and healthy subjects. Percent increase in heart rate from baseline was used to quantify cardiac ANS response, while percent decrease in PPG amplitude represented degree of peripheral vasoconstriction. After employing cluster analysis to determine threshold levels, the HUT responses were classified into four phenotypes: (CP) increased heart rate and peripheral vasoconstriction; (C) increased heart rate only; (P) peripheral vasoconstriction only; and (ST) subthreshold cardiac and peripheral vascular responses. Multinomial logistic regression (MLR) was used to relate these phenotypic responses to various parameters representing blood properties and baseline cardiovascular activity. The most common phenotypic response, CP, was found in 82% of non-SCD subjects, including those with chronic anemia. In contrast, 70% of SCD subjects responded abnormally to HUT: C-phenotype = 22%, P-phenotype = 37%, or ST-phenotype = 11%. MLR revealed that the HUT phenotypes were significantly associated with baseline cardiac parasympathetic activity, baseline peripheral vascular variability, hemoglobin level and SCD diagnosis. Low parasympathetic activity at baseline dramatically increased the probability of belonging to the P-phenotype in SCD subjects, even after adjusting for hemoglobin level, suggesting a characteristic autonomic dysfunction that is independent of anemia. Further analysis using a mathematical model of heart rate variability revealed that the low parasympathetic activity in P-phenotype SCD subjects was due to impaired respiratory-cardiac coupling rather than reduced cardiac baroreflex sensitivity. By having strong peripheral vasoconstriction without compensatory cardiac responses, P-phenotype subjects may be at increased risk for vaso-occlusive crisis. The classification of autonomic phenotypes based on HUT response may have potential use for guiding therapeutic interventions to alleviate the risk of adverse outcomes in SCD.

Project description:Introduction: Tilt tables enable early mobilization of patients by providing verticalization. But there is a high risk of orthostatic hypotension provoked by verticalization, especially after neurological diseases such as spinal cord injury. Robot-assisted tilt tables might be an alternative as they add passive robotic leg exercise (PE) that can be enhanced with functional electrical stimulation (FES) to the verticalization, thus reducing the risk of orthostatic hypotension. We hypothesized that the influence of PE on the cardiovascular system during verticalization (i.e., head-up tilt) depends on the verticalization angle, and FES strengthens the PE influence. To test our hypotheses, we investigated the PE effects on the cardiovascular parameters heart rate (HR), and systolic and diastolic blood pressures (sBP, dBP) at different angles of verticalization in a healthy population. Methods: Ten healthy subjects on a robot-assisted tilt table underwent four different study protocols while HR, sBP, and dBP were measured: (1) head-up tilt to 60° and 71° without PE; (2) PE at 20°, 40°, and 60° of head-up tilt; (3) PE while constant FES intensity was applied to the leg muscles, at 20°, 40°, and 60° of head-up tilt; (4) PE with variation of the applied FES intensity at 0°, 20°, 40°, and 60° of head-up tilt. Linear mixed models were used to model changes in HR, sBP, and dBP responses. Results: The models show that: (1) head-up tilt alone resulted in statistically significant increases in HR and dBP, but no change in sBP. (2) PE during head-up tilt resulted in statistically significant changes in HR, sBP, and dBP, but not at each angle and not always in the same direction (i.e., increase or decrease of cardiovascular parameters). Neither adding (3) FES at constant intensity to PE nor (4) variation of FES intensity during PE had any statistically significant effects on the cardiovascular parameters. Conclusion: The effect of PE on the cardiovascular system during head-up tilt is strongly dependent on the verticalization angle. Therefore, we conclude that orthostatic hypotension cannot be prevented by PE alone, but that the preventive effect depends on the verticalization angle of the robot-assisted tilt table. FES (independent of intensity) is not an important contributing factor to the PE effect.

Project description:Introduction: Robot-assisted tilt table therapy was proposed for early rehabilitation and mobilization of patients after diseases such as stroke. A robot-assisted tilt table with integrated passive robotic leg exercise (PE) mechanism has the potential to prevent orthostatic hypotension usually provoked by verticalization. In a previous study with rather young healthy subjects [average age: 25.1 ± 2.6 years (standard deviation)], we found that PE effect on the cardiovascular system depends on the verticalization angle of the robot-assisted tilt table. In the current study, we investigated in an older population of neurological patients (a) whether they show the same PE effects as younger healthy population on the cardiovascular system at different tilt angles, (b) whether changing the PE frequency (i.e., stepping speed) influences the PE effect on the cardiovascular system, (c) whether PE could prevent orthostatic hypotension, and finally, (d) whether PE effect is consistent from day to day. Methods: Heart rate (HR), and systolic and diastolic blood pressures (sBP, dBP) in response to PE at two different tilt angles (? = 20°, 60°) with three different PE frequencies (i.e., 0, 24, and 48 steps per minute) of 10 neurological patients [average age: 68.4 ± 13.5 years (standard deviation)] were measured on 2 consecutive days. Linear mixed models were used to develop statistical models and analyze the repeated measurements. Results: The models show that: PE significantly increased sBP and dBP but had no significant effect on HR. (a) Similar to healthy subjects the effect of PE on sBP was dependent on the tilt angle with higher tilt angles resulting in a higher increase. Head-up tilting alone significantly increased HR and dBP but resulted in a non-significant drop in sBP. PE, in general, had a more additive effect on increasing BP. (b) The effect of PE was not influenced by its speed. (c) Neither during head-up tilt alone nor in combination with PE did participants experience orthostatic hypotension. (d) The measurement day was not a statistically significant factor regarding the effects of verticalization and PE on the cardiovascular response. Conclusion: We provide evidence that PE can increase steady-state values of sBP and dBP in neurological patients during head-up tilt. Similar to healthy subjects the effect on sBP depends on the verticalization angle of the robot-assisted tilt table. PE might have the potential to prevent orthostatic hypotension, but as the amount of drop in BP in response to head-up tilting was not leading to orthostatic hypotension in our patients, we could neither conclude nor reject such a preventive compensatory effect. Furthermore, we found that changing the PE speed does not influence the steady-state cardiovascular response.

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Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test.

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Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test.

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