title: Prediction of extravascular burden of carbon monoxide (CO) in the human heart.
abstract: 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.
authors.affiliation: Center for Biomedical Engineering, University of Kentucky, Lexington, KY 40506-0070, USA. kinnerarey@uky.edu
authors.forename: Kinnera
authors.initials: K
authors.lastname: Erupaka
authors.forename: Eugene N
authors.initials: EN
authors.lastname: Bruce
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Bruce
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000097:blood*; D002249:Carbon Monoxide Poisoning / Q000150:complications* / Q000503:physiopathology*; D003198:Computer Simulation; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D017682:Myocardial Stunning / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D002248:Carbon Monoxide