TY  - JOUR
AU  - Jovanović, Slađana
AU  - Skorić, Tamara
AU  - Sarenac, Olivera
AU  - Milutinović-Smiljanić, Sanja
AU  - Japundžić-Žigon, Nina
AU  - Bajić, Dragana
PY  - 2018
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2291
AB  - Objectives: Copula is a tool for measuring linear and non-linear interactions between two or more time series. The aim of this paper is to prove that a copula approach can accurately capture and visualize the spatial and temporal fluctuations in dependency structures of cardiovascular signals, and to outline the application possibilities. Methods: The method for measuring the level of interaction between systolic blood pressure and the corresponding pulse interval is validated statistically and pharmacologically. The time series are recorded from the freely moving male Wistar rats equipped with radio-telemetry device for blood pressure recording, before and after administration of autonomic blockers scopolamine, atenolol, prazosin and hexamethonium. Implicit (Gaussian and t) and explicit (Clayton, Frank and Gumbel) copulas were calculated and compared to the conventional bivariate methods (Kendal, Pearson, Spearman and classical correlation). Further statistical validation was done using artificially generated surrogate data. A window sliding procedure for dynamic monitoring the signals' coupling strength is implemented. Results: Under the baseline physiological conditions, SBP-PI dependency is significant for time lags 0 s-4 s. Hexamethonium completely abolished the dependency, scopolamine abolished it for time lags 0 s-2 s, atenolol first slightly increased, than for lags greater than 2 s decreased the dependency and prazosin had no effect. Isospectral and isodistributional surrogate data tests confirm that copulas successfully notify the absence of dependency as well. Conclusion: Copula approach accurately captures the temporal fluctuations in dependency structures of SBP and PI, simultaneously enabling a visualization of dependency levels within the particular signal zones. An analysis showed that copulas are more sensitive than the conventional statistical measures, with Frank copula exhibiting the best characterization of SBP and PI dependency.
PB  - Elsevier Sci Ltd, Oxford
T2  - Biomedical Signal Processing & Control
T1  - Copula as a dynamic measure of cardiovascular signal interactions
VL  - 43
SP  - 250
EP  - 264
DO  - 10.1016/j.bspc.2018.03.007
ER  - 

@article{
author = "Jovanović, Slađana and Skorić, Tamara and Sarenac, Olivera and Milutinović-Smiljanić, Sanja and Japundžić-Žigon, Nina and Bajić, Dragana",
year = "2018",
abstract = "Objectives: Copula is a tool for measuring linear and non-linear interactions between two or more time series. The aim of this paper is to prove that a copula approach can accurately capture and visualize the spatial and temporal fluctuations in dependency structures of cardiovascular signals, and to outline the application possibilities. Methods: The method for measuring the level of interaction between systolic blood pressure and the corresponding pulse interval is validated statistically and pharmacologically. The time series are recorded from the freely moving male Wistar rats equipped with radio-telemetry device for blood pressure recording, before and after administration of autonomic blockers scopolamine, atenolol, prazosin and hexamethonium. Implicit (Gaussian and t) and explicit (Clayton, Frank and Gumbel) copulas were calculated and compared to the conventional bivariate methods (Kendal, Pearson, Spearman and classical correlation). Further statistical validation was done using artificially generated surrogate data. A window sliding procedure for dynamic monitoring the signals' coupling strength is implemented. Results: Under the baseline physiological conditions, SBP-PI dependency is significant for time lags 0 s-4 s. Hexamethonium completely abolished the dependency, scopolamine abolished it for time lags 0 s-2 s, atenolol first slightly increased, than for lags greater than 2 s decreased the dependency and prazosin had no effect. Isospectral and isodistributional surrogate data tests confirm that copulas successfully notify the absence of dependency as well. Conclusion: Copula approach accurately captures the temporal fluctuations in dependency structures of SBP and PI, simultaneously enabling a visualization of dependency levels within the particular signal zones. An analysis showed that copulas are more sensitive than the conventional statistical measures, with Frank copula exhibiting the best characterization of SBP and PI dependency.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Biomedical Signal Processing & Control",
title = "Copula as a dynamic measure of cardiovascular signal interactions",
volume = "43",
pages = "250-264",
doi = "10.1016/j.bspc.2018.03.007"
}

Jovanović, S., Skorić, T., Sarenac, O., Milutinović-Smiljanić, S., Japundžić-Žigon, N.,& Bajić, D.. (2018). Copula as a dynamic measure of cardiovascular signal interactions. in Biomedical Signal Processing & Control
Elsevier Sci Ltd, Oxford., 43, 250-264.
https://doi.org/10.1016/j.bspc.2018.03.007

Jovanović S, Skorić T, Sarenac O, Milutinović-Smiljanić S, Japundžić-Žigon N, Bajić D. Copula as a dynamic measure of cardiovascular signal interactions. in Biomedical Signal Processing & Control. 2018;43:250-264.
doi:10.1016/j.bspc.2018.03.007 .

Jovanović, Slađana, Skorić, Tamara, Sarenac, Olivera, Milutinović-Smiljanić, Sanja, Japundžić-Žigon, Nina, Bajić, Dragana, "Copula as a dynamic measure of cardiovascular signal interactions" in Biomedical Signal Processing & Control, 43 (2018):250-264,
https://doi.org/10.1016/j.bspc.2018.03.007 . .

TY  - JOUR
AU  - Milutinović-Smiljanić, Sanja
AU  - Sarenac, Olivera
AU  - Lozic-Đurić, Maja
AU  - Murphy, David
AU  - Japundžić-Žigon, Nina
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1834
AB  - Background and Purpose It is well recognized that vasopressin modulates the neurogenic control of the circulation. Here, we report the central mechanisms by which vasopressin modulates cardiovascular response to stress induced by immobilization. Experimental Approach Experiments were performed in conscious male Wistar rats equipped with radiotelemetric device for continuous measurement of haemodynamic parameters: systolic and diastolic BP and heart rate (HR). The functioning of the spontaneous baro-receptor reflex (BRR) was evaluated using the sequence method and the following parameters were evaluated: BRR sensitivity (BRS) and BRR effectiveness index (BEI). Key Results Under baseline physiological conditions intracerebroventricular injection of 100 and 500ng of selective non-peptide V1a or V1b or V2 receptor antagonist did not modify BP, HR and BRR. Rats exposed to 15min long stress by immobilization exhibited increase of BP, HR, reduction of BRS and no change in BEI. Pretreatment of rats with V1a receptor antagonist did not modulate the BP, HR, BRS and BEI response to stress. Pretreatment of rats with V1b receptor and V2 receptor antagonist, at both doses, prevented BRR desensitization and tachycardia, but failed to modulate stress-induced hypertension. Conclusions and Implications Vasopressin by the stimulation of central V1b- and V2-like receptors mediates stress-induced tachycardia and BRR desensitization. If these mechanisms are involved, BRR desensitization in heart failure and hypertension associated with poor outcome, they could be considered as novel targets for cardiovascular drug development.
PB  - Wiley-Blackwell, Hoboken
T2  - British Journal of Pharmacology
T1  - Evidence for involvement of central vasopressin V1b and V2 receptors in stress-induced baroreflex desensitization
VL  - 169
IS  - 4
SP  - 900
EP  - 908
DO  - 10.1111/bph.12161
ER  - 

@article{
author = "Milutinović-Smiljanić, Sanja and Sarenac, Olivera and Lozic-Đurić, Maja and Murphy, David and Japundžić-Žigon, Nina",
year = "2013",
abstract = "Background and Purpose It is well recognized that vasopressin modulates the neurogenic control of the circulation. Here, we report the central mechanisms by which vasopressin modulates cardiovascular response to stress induced by immobilization. Experimental Approach Experiments were performed in conscious male Wistar rats equipped with radiotelemetric device for continuous measurement of haemodynamic parameters: systolic and diastolic BP and heart rate (HR). The functioning of the spontaneous baro-receptor reflex (BRR) was evaluated using the sequence method and the following parameters were evaluated: BRR sensitivity (BRS) and BRR effectiveness index (BEI). Key Results Under baseline physiological conditions intracerebroventricular injection of 100 and 500ng of selective non-peptide V1a or V1b or V2 receptor antagonist did not modify BP, HR and BRR. Rats exposed to 15min long stress by immobilization exhibited increase of BP, HR, reduction of BRS and no change in BEI. Pretreatment of rats with V1a receptor antagonist did not modulate the BP, HR, BRS and BEI response to stress. Pretreatment of rats with V1b receptor and V2 receptor antagonist, at both doses, prevented BRR desensitization and tachycardia, but failed to modulate stress-induced hypertension. Conclusions and Implications Vasopressin by the stimulation of central V1b- and V2-like receptors mediates stress-induced tachycardia and BRR desensitization. If these mechanisms are involved, BRR desensitization in heart failure and hypertension associated with poor outcome, they could be considered as novel targets for cardiovascular drug development.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "British Journal of Pharmacology",
title = "Evidence for involvement of central vasopressin V1b and V2 receptors in stress-induced baroreflex desensitization",
volume = "169",
number = "4",
pages = "900-908",
doi = "10.1111/bph.12161"
}

Milutinović-Smiljanić, S., Sarenac, O., Lozic-Đurić, M., Murphy, D.,& Japundžić-Žigon, N.. (2013). Evidence for involvement of central vasopressin V1b and V2 receptors in stress-induced baroreflex desensitization. in British Journal of Pharmacology
Wiley-Blackwell, Hoboken., 169(4), 900-908.
https://doi.org/10.1111/bph.12161

Milutinović-Smiljanić S, Sarenac O, Lozic-Đurić M, Murphy D, Japundžić-Žigon N. Evidence for involvement of central vasopressin V1b and V2 receptors in stress-induced baroreflex desensitization. in British Journal of Pharmacology. 2013;169(4):900-908.
doi:10.1111/bph.12161 .

Milutinović-Smiljanić, Sanja, Sarenac, Olivera, Lozic-Đurić, Maja, Murphy, David, Japundžić-Žigon, Nina, "Evidence for involvement of central vasopressin V1b and V2 receptors in stress-induced baroreflex desensitization" in British Journal of Pharmacology, 169, no. 4 (2013):900-908,
https://doi.org/10.1111/bph.12161 . .

TY  - JOUR
AU  - Stojičić, Sonja
AU  - Milutinović-Smiljanić, Sanja
AU  - Sarenac, Olivera
AU  - Milosavljević, S.
AU  - Paton, J. F. R.
AU  - Murphy, David
AU  - Japundžić-Žigon, Nina
PY  - 2008
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1431
AB  - To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V-1a (SR49059), V-1b (SSR 149415), V-2 (SR 121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LFBP and LF/HFHR). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LFBP oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V-1a, V-1b and V-2, receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V-1b and V-2 receptor antagonists reduced BPMAX whereas V-1a, V-1b antagonist and diazepam reduced HRMAX induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LFBP without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V-1b receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Neuropharmacology
T1  - Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats
VL  - 54
IS  - 5
SP  - 824
EP  - 836
DO  - 10.1016/j.neuropharm.2007.12.013
ER  - 

@article{
author = "Stojičić, Sonja and Milutinović-Smiljanić, Sanja and Sarenac, Olivera and Milosavljević, S. and Paton, J. F. R. and Murphy, David and Japundžić-Žigon, Nina",
year = "2008",
abstract = "To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V-1a (SR49059), V-1b (SSR 149415), V-2 (SR 121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LFBP and LF/HFHR). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LFBP oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V-1a, V-1b and V-2, receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V-1b and V-2 receptor antagonists reduced BPMAX whereas V-1a, V-1b antagonist and diazepam reduced HRMAX induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LFBP without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V-1b receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Neuropharmacology",
title = "Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats",
volume = "54",
number = "5",
pages = "824-836",
doi = "10.1016/j.neuropharm.2007.12.013"
}

Stojičić, S., Milutinović-Smiljanić, S., Sarenac, O., Milosavljević, S., Paton, J. F. R., Murphy, D.,& Japundžić-Žigon, N.. (2008). Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats. in Neuropharmacology
Pergamon-Elsevier Science Ltd, Oxford., 54(5), 824-836.
https://doi.org/10.1016/j.neuropharm.2007.12.013

Stojičić S, Milutinović-Smiljanić S, Sarenac O, Milosavljević S, Paton JFR, Murphy D, Japundžić-Žigon N. Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats. in Neuropharmacology. 2008;54(5):824-836.
doi:10.1016/j.neuropharm.2007.12.013 .

Stojičić, Sonja, Milutinović-Smiljanić, Sanja, Sarenac, Olivera, Milosavljević, S., Paton, J. F. R., Murphy, David, Japundžić-Žigon, Nina, "Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats" in Neuropharmacology, 54, no. 5 (2008):824-836,
https://doi.org/10.1016/j.neuropharm.2007.12.013 . .

TY  - JOUR
AU  - Stojičić, Sonja
AU  - Milutinović-Smiljanić, Sanja
AU  - Sarenac, Olivera
AU  - Živković, Slavoljub
AU  - Japundžić-Žigon, Nina
PY  - 2006
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1316
AB  - This study investigates the contribution of central vasopressin receptors in the modulation of systolic arterial pressure (SAP) and heart rate (HR) response to air-jet stress in conscious Wistar rats equipped with a femoral arterial catheter and intracerebroventricular cannula using novel non-peptide and selective vasopressin V, (SR49059) and V-1b (SSR149415) antagonists. The effects of stress on SAP and HR were evaluated by measuring the maximal response to stress, the latency of the maximal response, the duration of the recovery period, and the increase in the low frequency (LF) short-term variability component. Stress induced a parallel and almost immediate increase in both SAP and HR, followed by enhanced LF SAP variability in the recovery period. Pretreatment of rats with V-1a antagonist did not affect the maximal increase or the latency of SAP and HR response to acute stress, but shortened the recovery period of SAP and HR and prevented the increase in LF SAP. The V-1b antagonist reduced the maximal increase in SAP without affecting HR and their latencies, shortened the recovery period of SAP and inhibited the increase in LF SAP variability. These results indicate that both central V-1a and V-1b receptors mediate cardiovascular changes induced by air-jet stress in conscious rats.
PB  - Walter De Gruyter Gmbh, Berlin
T2  - Biomedizinische Technik
T1  - Central vasopressin V-1a and V-1b receptors modulate the cardiovascular response to air-jet stress in conscious rats
VL  - 51
IS  - 4
SP  - 268
EP  - 271
DO  - 10.1515/BMT.2006.053
ER  - 

@article{
author = "Stojičić, Sonja and Milutinović-Smiljanić, Sanja and Sarenac, Olivera and Živković, Slavoljub and Japundžić-Žigon, Nina",
year = "2006",
abstract = "This study investigates the contribution of central vasopressin receptors in the modulation of systolic arterial pressure (SAP) and heart rate (HR) response to air-jet stress in conscious Wistar rats equipped with a femoral arterial catheter and intracerebroventricular cannula using novel non-peptide and selective vasopressin V, (SR49059) and V-1b (SSR149415) antagonists. The effects of stress on SAP and HR were evaluated by measuring the maximal response to stress, the latency of the maximal response, the duration of the recovery period, and the increase in the low frequency (LF) short-term variability component. Stress induced a parallel and almost immediate increase in both SAP and HR, followed by enhanced LF SAP variability in the recovery period. Pretreatment of rats with V-1a antagonist did not affect the maximal increase or the latency of SAP and HR response to acute stress, but shortened the recovery period of SAP and HR and prevented the increase in LF SAP. The V-1b antagonist reduced the maximal increase in SAP without affecting HR and their latencies, shortened the recovery period of SAP and inhibited the increase in LF SAP variability. These results indicate that both central V-1a and V-1b receptors mediate cardiovascular changes induced by air-jet stress in conscious rats.",
publisher = "Walter De Gruyter Gmbh, Berlin",
journal = "Biomedizinische Technik",
title = "Central vasopressin V-1a and V-1b receptors modulate the cardiovascular response to air-jet stress in conscious rats",
volume = "51",
number = "4",
pages = "268-271",
doi = "10.1515/BMT.2006.053"
}

Stojičić, S., Milutinović-Smiljanić, S., Sarenac, O., Živković, S.,& Japundžić-Žigon, N.. (2006). Central vasopressin V-1a and V-1b receptors modulate the cardiovascular response to air-jet stress in conscious rats. in Biomedizinische Technik
Walter De Gruyter Gmbh, Berlin., 51(4), 268-271.
https://doi.org/10.1515/BMT.2006.053

Stojičić S, Milutinović-Smiljanić S, Sarenac O, Živković S, Japundžić-Žigon N. Central vasopressin V-1a and V-1b receptors modulate the cardiovascular response to air-jet stress in conscious rats. in Biomedizinische Technik. 2006;51(4):268-271.
doi:10.1515/BMT.2006.053 .

Stojičić, Sonja, Milutinović-Smiljanić, Sanja, Sarenac, Olivera, Živković, Slavoljub, Japundžić-Žigon, Nina, "Central vasopressin V-1a and V-1b receptors modulate the cardiovascular response to air-jet stress in conscious rats" in Biomedizinische Technik, 51, no. 4 (2006):268-271,
https://doi.org/10.1515/BMT.2006.053 . .