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.

Keywords::

• Brain function
• Carbon monoxide
• CO
• exercise
• vascular disease

Acknowledgments

The authors wish to thank the Drs. Dan Costa, Doug Johns, and Beth Owens for their helpful suggestions and preview of the manuscript.

Declaration of interest

This work was entirely funded by internal US EPA funds. The manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.