While many physiological control models exist in the literature, none thus far has focused on characterizing the interactions among the respiratory, cardiovascular and sleep-wake regulation systems that occur in sleep-disordered breathing. The model introduced in this study integrates the autonomic control of the cardiovascular system, chemoreflex and state-related control of respiration, including respiratory and upper airway mechanics, along with a model of circadian and sleep-wake regulation. The integrative model provides realistic predictions of the physiological responses under a variety of conditions including: the sleep-wake cycle, hypoxiainduced periodic breathing, Cheyne-Stokes respiration in chronic heart failure, and obstructive sleep apnoea (OSA). It can be used to investigate the effects of a variety of interventions, such as isocapnic and hypercapnic and/or hypoxic gas administration, the Valsalva and Mueller maneuvers, and the application of continuous positive airway pressure on OSA subjects. By being able to delineate the influences of the various interacting physiological mechanisms, the model is useful in providing a more lucid understanding of the complex dynamics that characterize statecardiorespiratory control in the different forms of sleep-disordered breathing.

11. MODEL DESCRIPTION Absnaa-The dynamic interactions among the peripheral inputs that originate from the chemoreflexes, baroreflexes and pulmonary stretch receptors, together with central autonomic Cardiovascular System -Components in this system include coupling between respiratory and cardiovascular efferents, a nonlinear carotid sinus compartment stimulated hy the play important roles in determining the physiological effects arterial blood pressure, a sino-atrial node component that that accompany sleep-disordered breathing. However, regulates the heart rate with both parasympathetic and previous modeling studies have focussed primarily on specific sympathetic controls, a peripheral resistance component regions of interest. The purpose ofthis study was to integrate controlled the alpha-sympathetic activity,,a hemodynamic submodel based on a simple two-element Windkessel the key features of existing cardiovascular and respiratory models into a comprehensive model that is capable of simulating the dynamics of cardiorespiratory control during model, and a component that controk changes in stroke wakefulness and sleep. PNEUMA is implemented using volume via changes in the venous return and cardiac SIMULINP (The Mathworks, Natick, MA), which provides a contractility [I].graphical environment that allows the nser to easily convert Respiratory System -The respiratory compartments include control block diagrams into networks of blocks of both the mechanical and the gas-exchange components. mathematical functions. The advantages of PNEUMA lie in: (1) the modularity of its various components; (2) the flexibility with which changes can be made to selected portions of the program; and (3) transportability ofthe model across different computer platforms and operating systems.