Whole‐Body Carbon Monoxide Production In Normal Adult Human Volunteers

Abstract

BACKGROUNDHumans and other mammals break down heme to generate carbon monoxide (CO) in a reaction that is catalyzed by heme oxygenase (HO). It is well documented that CO can bind to nitric oxide synthase to inhibit nitric oxide formation. Numerous studies have also shown that increased HO expression and subsequent CO formation inhibit nitric oxide production resulting in endothelial dysfunction. These findings have been demonstrated in numerous pathological animal models and in intubated trauma patients. Past clinical studies, measuring whole body CO formation have required patients to be placed in sealed chambers or intubated. Such restrictions have made it difficult to readily assess CO formation in patients. In an attempt to overcome these limitations, we have developed a technique to measure whole‐body CO excretion without the complexity of sequestration or intubation.APPLICATIONThe earliest studies noting CO generation in humans reported that carboxyhemoglobin levels are elevated in females, specifically during estrus. It has also been reported that that estrogen will induce the expression of HO. Accordingly we hypothesized that females will generate higher rates of whole‐body CO generation in comparison to males; furthermore rates of CO generation will be additionally exaggerated during estrus.METHODSMale and female volunteers were fitted with masks to measure minute volume ventilation using a non‐recirculating circuit. Samples of exhaled breath were collected and assayed for CO content via solid‐phase gas chromatography. For each subject, the whole‐body CO excretion was calculated as the product of the CO concentration and minute volume ventilation; excretion was normalized to body weight.RESULTSOur measurements of whole‐body CO excretion using our newly developed technique were in accordance with those previously reported in intubated male trauma patients. However, in this series we learned that CO excretion in females is not higher than in males (p > 0.05). Furthermore, rates of CO excretion during estrus are not elevated when compared to the rest of the menstrual cycle.CONCLUSIONSWhole body CO formation is not elevated during estrus so reports of elevated carboxyhemoglobin levels may be the result of changes in hemoglobin activities, but not the result of enhanced CO formation per se.Support or Funding InformationWilliam Carey University College of Osteopathic MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.