Modeling of Autonomic, Metabolic and Vascular Control Interactions
Michael C.K. Khoo, Ph.D.
Project Leader
The long-term goal of this project is to extend the minimal and structured modeling approaches that we have developed and successfully applied in the study of state-cardiorespiratory control to incorporate interactions with other physiological subsystems, such as glucose-insulin control and the control of peripheral vascular function. The knowledge gained would be useful in improving our understanding and providing a quantitative, dynamic characterization of the key interactions that underlie multi-factor disease syndromes, such as the combination of metabolic syndrome and sleep-disordered breathing, and vaso-occlusive episodes in sickle-cell anemia. The models derived from the proposed investigations could lead to novel, noninvasive methods for the early detection of the deleterious consequences of these diseases or improvements in the associated therapeutic interventions. As steps towards achieving the overall goal, we propose to address the following specific aims:
(1) To develop an extended model of autonomic-metabolic interaction, based on existing “minimal” models of autonomic cardiovascular control and glucose-insulin control, and to determine how the extended model parameters are affected in disease.
(2) To elucidate the time-varying characteristics of the model of autonomic-metabolic interaction in relation to changes in sleep-wake state, and to determine how these characteristics may be altered in disease.
(3) To determine the relationships between the parameters of the model of autonomic control and the factors that regulate blood flow through the peripheral microvasculature in health and disease (eg. sickle-cell anemia and diabetes).
(4) To develop a comprehensive structured model, based on PNEUMA, that reflects state-of-the-art knowledge about the physiological mechanisms that link the respiratory, cardiovascular, sleep-wake, and metabolic control systems. As well, new information derived from the extended minimal model will be incorporated into the structured model.
(5)
To incorporate structural changes into PNEUMA that would enhance its
ability to simulate the effects of disease progression and the effects
of long-term pharmacological intervention
Selected Publications
Khoo, M.C.K. Modeling autonomic control in sleep-disordered breathing. Cardiovascular Engineering 8:30-41, 2008. [PDF – 558 KB]
Chaicharn, J., M. Carrington, J. Trinder and M.C.K. Khoo. The effects on autonomic control of repetitive arousal from sleep. Sleep 31:93-103, 2008. [PDF – 688 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]
