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.
Inhal Toxicol. 2010 Apr;22(5):417-26. doi: 10.3109/08958370903576806.
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.
在某种程度上，由于吸入一氧化碳 (CO) 而导致的碳氧血红蛋白 (COHb) 会缩短正常人和缺血性心脏病患者的最大运动持续时间。在正常受试者中，当 COHb 水平较高时，大脑功能也会受到影响，行为表现会受损。这些发现来自已发表的实验，但由于伦理或实际考虑，这些实验并不完整，没有很好地研究 COHb 更高或更低的范围以及运动水平。为了填补这一知识空白，使用全身人体生理模型通过模拟对 CO 和各种运动水平的参数暴露来估计生理功能。通过在左心动脉供应中引入狭窄来模拟缺血性心脏病。大脑血流量也受到这样的狭窄限制。为了使这种估计具有可信度，该模型通过模拟已发表文献中的实验进行了测试。模拟允许得出几个新的结论。当运动最不剧烈且 COHb 最小时，COHb 的增加会导致运动持续时间的最大减少。对于缺血性心脏病患者，COHb 增加导致运动持续时间变化最大的情况是在缺血和 COHb 最小时。除非最大脑血流量受到大于正常 50%的狭窄限制，否则 COHb 超过 25%不会影响脑需氧代谢。对于更高水平的狭窄，任何 COHb 水平的增加都会导致脑需氧代谢减少，这意味着如果没有 COHb 的“阈值”，行为将会受损。
