title: Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.
abstract: At some level, carboxyhemoglobin (COHb) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in both normal and ischemic heart patients. At high COHb levels in normal subjects, brain function is also affected and behavioral performance is impaired.These are findings from published experiments that are, due to ethical or practical considerations, incomplete in that higher or lower ranges of COHb, and exercise have not been well studied. To fill in this knowledge base, a whole-body human physiological model was used to make estimates of physiological functioning by the simulation of parametric exposures to CO and various exercise levels. Ischemic heart disease was simulated by introducing a stenosis in the left heart arterial supply. Brain blood flow was also limited by such a stenosis. To lend credibility to such estimation, the model was tested by simulating experiments from the published literature. Simulations permitted several new conclusions. Increases in COHb produced the largest decreases in exercise duration when exercise was least strenuous and when COHb was smallest. For ischemic heart disease subjects, the greatest change in exercise duration produced by COHb increase was when ischemia and COHb was smallest. Brain aerobic metabolism was unaffected until COHb exceeded 25%, unless the maximum brain blood supply was limited by a stenosis greater than 50% of normal. For higher levels of stenosis, aerobic brain metabolism was reduced for any increase in COHb level, implying that behavior would be impaired with no "threshold" for COHb.
authors.affiliation: Integrated Systems Toxicology Division, Systems Biology Branch, Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA. tbenignus@earthlink.net
authors.forename: Vernon A
authors.initials: VA
authors.lastname: Benignus
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Coleman
mesh_terms: D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D002248:Carbon Monoxide / Q000032:analysis / Q000633:toxicity*; D002263:Carboxyhemoglobin / Q000032:analysis; D003198:Computer Simulation; D004784:Environmental Monitoring; D015444:Exercise; D005080:Exercise Test; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology*
chemical_list: D002248:Carbon Monoxide; D002263:Carboxyhemoglobin