PNEUMA consists of a set of modules that are used to simulate the autoregulation of the cardiovascular and respiratory systems under conditions of changing sleep-wake state and a variety of physiological and pharmacological interventions. It models the dynamic interactions that take place among the various component mechanisms, including those involved in the chemical control of breathing, heart rate, and blood pressure, as well as the effects of changes in the sleep-wake state and arousal from sleep. PNEUMA includes the autonomic control of the cardiovascular system, chemoreflex and state-related control of breath-to-breath ventilation, state-related and chemoreflex control of upper airway potency, as well as respiratory and circulatory mechanics. The model is capable of simulating the cardiorespiratory responses to sleep onset, arousal, continuous positive airway pressure, the administration of inhaled carbon dioxide and oxygen, Valsalva and Mueller maneuvers, and Cheyne-Stokes respiration during sleep.

In PNEUMA 3.0, we have extended the existing integrative model of respiratory, cardiovascular, and sleep–wake state control, to incorporate a sub-model of glucose–insulin–fatty acid regulation. The extended model is capable of simulating the metabolic control of glucose–insulin dynamics and its interactions with the autonomic nervous system. The interactions between autonomic and metabolic control include the circadian regulation of epinephrine secretion, epinephrine regulation on dynamic fluctuations in glucose and free fatty acids in plasma, metabolic coupling among tissues and organs mediated by insulin and epinephrine, as well as the effect of insulin on peripheral vascular sympathetic activity. This extended model represents a starting point from which further in silico investigations into the interaction between the autonomic nervous system and the metabolic control system can proceed.

PNEUMA has been developed as a part of the Service function of the Biomedical Simulations Resource (BMSR) in the Department of Biomedical Engineering at the University of Southern California, under support from the National Institute for Biomedical Imaging and Bioengineering (P41-EB001978) and the National Center for Research Resources (P41-RR01861) of the National Institutes of Health.  It is distributed by the BMSR at no charge to the user, under the terms of a Release Agreement. We ask that all users of PNEUMA provide us with a completed Release Agreement, which will allow us to maintain a complete database of PNEUMA users. Please feel free to send your feedback or any questions to

System Requirements

PNEUMA requires Matlab R2007b or higher with the accompanying version of Simulink to be installed on your computer.

Features in PNEUMA 3.0

  • Incorporates metabolic component based on prior models of glucose-insulin regulation and free fatty acid (FFA) regulation.
  • Changes in sympathetic activity from the autonomic portion of PNEUMA produce changes in epinephrine output, which in turn affects the metabolic sub-model.
  • Inputs from the dietary intake of glucose and external interventions, such as insulin injections, have also been incorporated.
  • Also incorporated is autonomic “feedback” from the metabolic component to the rest of PNEUMA: changes in insulin level lead to changes in sympathetic tone.

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