A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats

A time-dependent simulation model, based on the Coburn-Forster-Kane equatio n, was written in Advanced Continuous Simulation Language to predict carbox yhemoglobin (HbCO) formation and dissociation in F-344 rats during and afte r exposure to 500 parts/million CO for 1 h. Blood-gas analysis and CO-oxime try were performed on samples collected during exposure and off-gassing of CO. Volume displacement plethysmography was used to measure minute ventilat ion (VE) during exposure. CO diffusing capacity in the lung (DLCO) was also measured. Other model parameters measured in the animals included blood pH , total blood volume, and Hb concentration. Comparisons between model predi ctions using values for (V) over dot(E), DLCO, and the Haldane coefficient cited in the literature and predictions using measured (V) over dot(E), DLC O, and calculated Haldane coefficient for individual animals were made. Gen eral model predictions using values for model parameters derived from the l iterature agreed with published HbCO values by a factor of 0.987 but failed to simulate experimental data. On average, the general model overpredicted measured HbCO level by nearly 9%. A specific model using the means of meas ured variables predicted HbCO concentration within a factor of 0.993. When experimentally observed parameter fluctuations were included, the specific model predictions reflected experimental effects on HbCO formation.