Dynamic Modeling of State-Cardiorespiratory Interactions
Michael C.K. Khoo, Ph.D. -
Project Leader
The fundamental premise of this research project is that the spontaneous variabilities observed in measurements of respiration, heart rate, blood pressure and sleep-wake state reflect the dynamics of complex interactions that take place among the underlying physiological mechanisms. Due to the abundance of feedback and feedforward connections within and across these mechanisms, it is generally difficult to delineate these mechanisms by applying traditional “open-loop” physiological techniques, particularly in studies involving human data. Thus, the long-term goal of this project is to elucidate the nature of these complex state-cardiorespiratory interactions through the parallel application of closed-loop minimal modeling and structural modeling approaches. However, the emphasis will be on minimal modeling: i.e. development of models in which all the parameters can be estimated from the available measurements. To attain this long-term goal, we have identified the following specific objectives:
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In previous work, attention was focused
primarily on developing the components of the closed-loop minimal model
that account for heart rate variability. In this phase of the project,
we extend and validate the development of the other half of the
closed-loop model that predicts blood pressure variability. More
specifically, we incorporate components that represent the baroreflex
control of peripheral resistance and variability in stroke volume,
features that are not represented in the current model.
- We expand the model to incorporate nonstationary and nonlinear characteristics pertinent to state-cardiorespiratory control. This approach is applied to determine how the major components of autonomic control vary during overnight sleep as a function of both sleep stage and time of night. We also extend the existing closed-loop minimal model to incorporate the dynamic effects on cardiovascular autonomic control of exposure to sustained or intermittent episodes of chemoreflex stimulation or intermittent arousals. In particular, this part of the study determines whether the model predicts the cumulative effects of overnight exposure to intermittent hypoxia or arousal on cardiovascular control.
- We determine whether certain parameters of the closed-loop minimal model can be used as reliable noninvasive markers of parasympathetic and sympathetic cardiovascular activation. As well, we determine whether the parameters that characterize the model nonlinearities are capable of detecting changes or abnormalities in autonomic function with greater sensitivity relative to the model parameters associated with linear dynamics.
- The information derived from our minimal modeling efforts will be used to further develop and refine a comprehensive structured model of sleep-cardiorespiratory physiology within the context of PNEUMA.
Selected Publications
Khoo, M.C.K. Modeling autonomic control in sleep-disordered breathing. Cardiovascular Engineering (in press).
Chaicharn, J., M. Carrington, J. Trinder and M.C.K. Khoo. The effects on cardiovascular autonomic control of repetitive arousal from sleep. Sleep 31:93-103, 2008. [PDF – 690 KB]
Jo, J., A. Blasi, E. Valladares, R. Juarez, A. Baydur and M.C.K. Khoo. A nonlinear model of cardiac autonomic control in obstructive sleep apnea syndrome. Annals of Biomedical Engineering 35(8):1425-1443, 2007. [PDF – 1,021 KB]
Asyali, M., R.B. Berry, M.C.K. Khoo and A. Altinok. Determining a continuous marker for sleep depth. Computers in Biology and Medicine 37(11):1600-1609, 2007. [PDF – 191 KB]
Blasi, A., J. Jo, E. Valladares, R. Juarez, A. Baydur and M.C.K. Khoo. Autonomic cardiovascular control following transient arousal from sleep: A time-varying closed-loop model. IEEE Transactions on Biomedical Engineering 53(1):74-82, 2006. [PDF – 539 KB]
Ivanova, O., L. Marcu and M.C.K. Khoo. A nonparametric method for analysis of fluorescence emission in combined time and wavelength dimensions. Annals of Biomedical Engineering 33(4):529-542, 2005. [PDF - 883 KB]
Jo, J., A. Blasi, E. Valladares, R. Juarez, A. Baydur and M.C.K. Khoo. Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep. American Journal of Physiology - Heart and Circulatory Physiology 288:H1103-H1112, 2005. [PDF - 744 KB]
Ivanova O.V., M.C.K. Khoo. Simulation of spontaneous cardiovascular variability using PNEUMA. Proc 26th Annual IEEE EMBS Conference, p.3901-3904, 2004.
Blasi, A., J. Jo, E. Valladares, B.J. Morgan, J.B. Skatrud, and M.C.K. Khoo. Cardiovascular variability after arousal from sleep: time-varying spectral analysis. J Appl Physiol 95:1394-1404, 2003. [PDF - 641 KB]
Blasi A., J. Jo, E. Valladares, R. Juarez, A. Baydur and M.C.K. Khoo. Time-varying analysis of autonomic control during arousal from sleep in obstructive sleep apnea syndrome. Proc 25th Annual EMBS Conference, p.350-353, 2003.
Jo J., A. Blasi, A. Baydur, R. Juarez and M.C.K. Khoo. Nonlinear assessment of autonomic function in obstructive sleep apnea during long-term CPAP therapy. Proc 25th Annual EMBS Conference, p.346-349, 2003.
Ivanova O.V., L. Marcu and M.C.K. Khoo. Estimation of optical fluorescent impulse response kernel in combined time and wavelength spaces. Proc. SPIE, Vol. 4955, p.330-341, 2003.
Belozeroff, V., R.B. Berry, & M.C.K. Khoo. Model-based assessment of autonomic control obstructive sleep apnea syndrome. Sleep 26(1):1-9, 2003. [PDF - 327 KB]
Belozeroff, V., R.B. Berry, C.S.H. Sassoon & M.C.K. Khoo. Effects of CPAP therapy on cardiovascular variability in obstructive sleep apnea: a closed-loop analysis. Am. J. Physiol. Heart Circ. Physiol., 282:H110-H121, 2002. [PDF - 223 KB]
Blasi, A., J. Jo, A. Baydur, R. Juarez & M.C.K. Khoo. Effects of arousal from sleep on autonomic cardiovascular control in obstructive sleep apnea syndrome. Proc. 2nd Joint EMBS-BMES Conference, p.1525-1526, 2002.
Fan H. & M.C.K. Khoo. PNEUMA: a comprehensive cardiorespiratory model. Proc 2nd Joint EMBS-BMES Conference, p.1533-1534, 2002.
Jo, J., M.C.K. Khoo, A. Blasi, A. Baydur & R. Juarez. Detection of autonomic abnormality in obstructive sleep apnea using a nonlinear model of heart rate variability. Proc. 2nd Joint EMBS-BMES Conference, p.1554-1555, 2002.
Fan H. & M.C.K. Khoo. Cardiorespiratory interactions in sleep-disordered breathing: an integrative model. Am. J. Respir. Crit. Care Med. 163(4):A630, 2001.
Garde, S., M.G. Regalado, V.L. Schechtman, & M.C.K. Khoo. Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep. Am J. Physiol. Heart Circ. Physiol, 280: H2920–H2928, 2001. [PDF - 244 KB]
Khoo, M.C.K., V. Belozeroff & R.B. Berry. Dynamics of heart rate control in obstructive sleep apnea: a minimal model. In: Cardiac autonomic control in obstructive sleep apnea: effects of long-term CPAP therapy. Am. J. Respir. Crit. Care Med.,Frontiers in Modeling and Control of Breathing: Integration at Molecular, Cellular, and Systems Levels, eds. C.-S. Poon and H. Kazemi, p. 465-470, Kluwer Academic: NY, 2001.
Khoo, M.C.K., V. Belozeroff, R.B. Berry & C.S.H. Sassoon. Cardiac autonomic control in obstructive sleep apnea: effects of long-term CPAP therapy. Am. J. Respir. Crit. Care Med., 164:807-812, 2001. [PDF - 108 KB]
Regalado, M., V. Schechtman and M.C.K. Khoo. Spectral analysis of heart rate variability and respiration during sleep in cocaine-exposed neonates. Clinical Physiology 21:428-436, 2001.
Khoo, M.C.K., T.S. Kim & R.B. Berry. Spectral indices of cardiac autonomic function in obstructive sleep apnea. Sleep, 22:443-451, 1999. [PDF - 187 KB]
