Clinically significant myocardial abnormalities (e.g., arrhythmias, S-T elevation) occur in patients with mild-to-severe carbon monoxide (CO) poisoning. We enhanced our previous whole body model [Bruce, E. N., M. C. Bruce, and K. Erupaka. Prediction of the rate of uptake of carbon monoxide from blood by extravascular tissues. Respir. Physiol. Neurobiol. 161(2):142-159, 2008] by adding a cardiac compartment (containing three vascular and two tissue subcompartments differing in capillary density) to predict myocardial carboxymyoglobin (MbCO) and oxygen tensions (P(c)O2) for several CO exposure regimens at rest and during exercise. Model predictions were validated with experimental data in normoxia, hypoxia, and hyperoxia. We simulated exposure at rest to 6462 ppm CO (10 min) and to 265 ppm CO (480 min), and during three levels of exercise at 20% HbCO. We compared responses of carboxyhemoglobin (HbCO), MbCO and P(c)O2 to estimate the potential for myocardial injury due to CO hypoxia. Simulation results predict that during CO exposures and subsequent therapies, cardiac tissue has higher MbCO levels and lower P(c)O2's than skeletal muscle. CO exposure during exercise further decreases P(c)O2 from resting levels. We conclude that in rest and moderate exercise, the myocardium is at greater risk for hypoxic injury than skeletal muscle during the course of CO exposure and washout. Because the model can predict CO uptake and distribution in human myocardium, it could be a tool to estimate the potential for hypoxic myocardial injury and facilitate therapeutic intervention.

Uptake of environmental carbon monoxide (CO) via the lungs raises the CO content of blood and of myoglobin (Mb)-containing tissues, but the blood-to-tissue diffusion coefficient for CO (DmCO) and tissue CO content are not easily measurable in humans. We used a multicompartment mathematical model to predict the effects of different values of DmCO on the time courses and magnitudes of CO content of blood and Mb-containing tissues when various published experimental studies were simulated. The model enhances our earlier model by adding mass balance equations for oxygen and by dividing the muscle compartment into two subcompartments. We found that several published experimental findings are compatible with either fast or slow rates of blood-tissue transfer of CO, whereas others are only compatible with slow rates of tissue uptake of CO. We conclude that slow uptake is most consistent with all of the experimental data. Slow uptake of CO by tissue is primarily due to the very small blood-to-tissue partial pressure gradients for CO.