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Mathematical Model of Ventilation Response to Inhaled Carbon Monoxide Stuhmiller & Stuhmiller, J Appl. Physiol. 98: 2033-44 (2005) Raymond Yakura May 31, 2006 BIOEN 589 Uses of Model Fires generate noxious gases • Results in increased carbon dioxide, increased carbon monoxide and reduced oxygen Dramatic effects on ventilation which vary with gas composition and exposure duration Model Summary Dynamic Physiological Model Authors used Matlab with Simulink Incorporates models from many different sources into one integrated model • Sources include Duffin et al., Ursino et al., Hill et al., Gomez, Roughton and Darling, Doblar et al. Results from Publication With CO acute inhalation, hyperventilation first results and then a subsequent ventilation depression • Hyperventilation caused by hypoxia which activates the peripheral chemoreceptors • Ventilation depression caused by generation of lactic acid in the brain and decreased brain activity Publication Results Buildup of carboxyhemoglobin with reduction in oxygen delivery to the brain leads to anaerobic glycolysis and buildup of lactate Model Subsets Metabolism • Oxygen metabolism, oxygen transfer to the brain, lactic acid generation, anaerobic limit Cardiac Output • Blood flow to the brain increases during hypoxia Circulatory System • Mass balance equations for O2, CO2 and CO Blood Chemistry • Hemoglobin saturation, O2 /CO partition, acid-base balance, CO2 dissociation Ventilation • Chemoreceptor response • Brain activity response • Combined ventilatory response Respiration System • Total ventilation and effects of dead space and humidification Model Schematic JSIM model JSim 1.6.62 used for this project Event driven to input O2, CO2 and CO Introduced memory into system to detect Lactate changes analogous to a D-Flip Flop in digital circuit design JSIM Model Results - Ventilation With increase in CO & CO2, and decrease of O2, ventilation initially increased and then decreased JSIM results – Lactate Generation Lactate generation in the brain due to increased anaerobic respiration due to hypoxia JSIM results: Brain activity Brain activity decreased due to lower pressure in the brain capillaries JSIM results: Tidal volume and Breathing Frequency Tidal volume increased due to CO2 increase Combined f (breathing frequency) started to initially increase due to chemoreceptors activation, but decreased later on due to lower brain activity JSIM results: CO2 components CO2 components • HCO3- is majority of the CO2 • Carbamino and CO2 in plasma is in small amounts of CO2 Model Limitations Article • Errors and notational changes in the article • Model Schematic and equations do not indicate a feedback loop, although the graphs implicitly indicate a feedback loop Model in JSIM • Not a feedback loop • P_O2_Brain and O2art are separate events • Convergence issues due to the number of equations and initiation values resulting in increasing the error tolerance that decreases accuracy.