Mathematical Model of Ventilation Response to Inhaled Carbon Monoxide

1. 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

2. 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

3. 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.

4. 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

5. Publication Results • Buildup of carboxyhemoglobin with reduction in oxygen delivery to the brain leads to anaerobic glycolysis and buildup of lactate

6. 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

7. Model Schematic

8. 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

9. JSIM Model Results - Ventilation • With increase in CO & CO2, and decrease of O2, ventilation initially increased and then decreased

10. JSIM results – Lactate Generation • Lactate generation in the brain due to increased anaerobic respiration due to hypoxia

11. JSIM results: Brain activity • Brain activity decreased due to lower pressure in the brain capillaries

12. 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

13. JSIM results: CO2 components • CO2 components • HCO3- is majority of the CO2 • Carbamino and CO2 in plasma is in small amounts of CO2

14. 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.