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Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.
Citation:
BENIGNUS, V. A. AND T. G. Coleman. Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 22(5):417-426, (2010).
Impact/Purpose:
A Well-established whole-body human mathematical model was used to estimate the effects of carboxyhemoglobin on exercise and brain function is normal and vascular-diseased perrsons. Results extren knowledge base well beyond previous data. These data could not have been obtained experimentally and may have regulatory utility.
Description:
At some level, carboxyhemoglobin (RbCO) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in normal and ischemic heart patients. At high RbCO levels in normal subjects, brain function is also affected and behavioral performance is impaired. These are findings from published experiments which are, due to ethical or practical considerations, incomplete in that higher or lower ranges of Hbf'O and exercise have not been well studied. To fill in this knowledge base, a whole-body human physiological model was used to make estimates ofphysiological functioning by the simulation ofparametric 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 RbCO produced the largest decreases in exercise duration when exercise was least strenuous and when RbCO was smallest. For ischemic heart disease subjects, the greatest change in exercise duration produced by RbCO increase was produced for the most moderate ischemia and smallest CORbo Brain aerobic metabolism was unaffected until RbCO exceeded 25% unless the maximum brain blood supply was limited by a stenosis greater than 50% ofnormal. For higher levels ofstenosis, aerobic brain metabolism was reduced for any increase in RbCO, implying that behavior would be impaired with no "threshold" for IlbCt). Key Words: Carbon monoxide, CO, exercise, brain function, vascular disease.
