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A model-based estimate of carbon monoxide uptake by heart muscle during exercise.

Authors
Bruce-E; Bruce-MC; Patwardhan-A
Source
Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R03-OH-008651, 2010 Aug; :1-11
Link
NIOSHTIC No.
20040437
Abstract
Exposure to carbon monoxide (CO) concentrations that exceed the Permissible Exposure Level (PEL) (50 ppm averaged over 8 hr) is the most common cause of work-related inhalation fatalities. The morbidity and mortality resulting from these CO exposures are due primarily to the effects of severe hypoxia on the heart and central nervous system. The long-standing practice of focusing on the carboxyhemoglobin (HbCO) level as the primary indicator of the severity of a CO exposure essentially ignores the CO load that accumulates in the extravascular tissues that are most vulnerable to a diminished oxygen supply such as the myocardium and brain. We propose that a predictive measure of the CO burden in these tissues during acute or chronic CO exposures in an occupational setting would provide a more accurate assessment of the risk associated with these exposures. The first aim of this proposal was to use existing data sets from human CO exposure studies to develop and enhance our mathematical model of whole-body CO uptake and distribution. We will use this model to predict CO and oxygen levels in blood and tissues of workers engaged in physical activity who are exposed to CO, both during the poisoning event and during therapy under room air or hyperoxia. All of our findings are based on simulation studies after developing mathematical models of whole-body CO uptake and distribution during CO exposures and therapies. Our modeling studies have shown repeatedly that therapies involving the breathing of 100% oxygen do lead to more rapid removal of CO from blood (than breathing air) but some of that CO diffuses into muscle and combines with myoglobin (Mb), where it may remain for hours. In rest and in situations of moderate physical activity, the myocardium is predicted to be at greater risk for hypoxic injury than skeletal muscle during the course of CO exposure and washout (therapy). The time course and depth of hypoxia in cardiac muscle during CO poisoning and therapy differs greatly from that in skeletal (exercising) muscles. Furthermore, the severity of tissue hypoxia in the myocardium is influenced by many factors. Consequently, the usual clinical index of severity of CO poisoning, the carboxyhemoglobin (HbCO) level, does not adequately reflect the potential for injury to the myocardium. We suggest that clinicians should be encouraged to obtain multi-lead electrocardiograms from all CO poisoning victims. Whole-body CO uptake and distribution during CO exposures and therapies occurs much more slowly than commonly assumed from the rate of uptake in the blood. Our findings strongly suggest that clinicians should not use HbCO level alone as a predictor of hypoxic injury of the myocardium (or of the brain), nor should they consider a fall in HbCO below some arbitrary level (e. g., 4%) as an indication that therapy for CO poisoning is no longer necessary. Further studies should be done to determine the optimal levels and durations of hyperoxic exposures given to CO poisoning victims to achieve washout of CO from the entire body (and not just from the blood). Our findings also indicate the importance of an awareness of the hemoglobin concentration in any worker likely to be exposed to ~ 30 ppm CO or more over an 8-hr day. As anemia is often amenable to therapeutic intervention, this should be the first consideration. If the worker's anemia is not correctable, it may be advisable to remove him/her from a setting in which exposure to CO is likely to occur. Removal from CO exposure would be even more important if the job also entailed exposure to particulates unless it could be demonstrated that the worker's minute ventilation was within the normal range. Our second objective was to determine the extent to which the predicted CO dose to the myocardium correlates with subtle changes in continuously-recorded electrocardiograms (ECGs) that are suggestive of hypoxia or ischemia. Despite having identified two possible sources of data for this aim, we were unsuccessful in acquiring appropriate data. The proposed data were inadequate because our simulations (discussed above) predicted the maximum impact of CO on the heart would occur at a time after the exposure ended, and recordings from this time period were unavailable. We have accomplished additional work not discussed in the original proposal. We modified one of our published models in order to examine the susceptibility of anemic women to CO hypoxia at rest and during elevated metabolism. Our model predictions confirmed the widely-held opinion that the severity of symptoms in anemic women does not correlate closely with Hb level. Workers with anemia may be somewhat more susceptible to CO poisoning; however, hyperventilation (which accompanies anemia) and the resulting exacerbation of particulate exposures that may occur in parallel with CO poisoning, may be a more significant concern. In other studies in collaboration with investigators from the Australian Institute of Sport, we have used simulations to validate two common clinical methods for estimating Hb mass and have characterized their limitations in much greater detail than can be done experimentally. Despite the fact that CO toxicity has been studied for many years, we have demonstrated in the studies supported by this grant that mathematical modeling can be used successfully to better understand the uptake and distribution of CO in exposed workers and to predict outcomes in individuals with anemia.
Keywords
Carbonyls; Exposure-levels; Exposure-limits; Inhalants; Morbidity-rates; Mortality-rates; Hypoxia; Nerve-damage; Nerve-function; Nervous-system-disorders; Nervous-system-function; Neurological-diseases; Neuromotor-system-disorders; Neuromuscular-system-disorders; Oxygen-toxicity; Myocardium; Brain-damage; Brain-function; Risk-factors; Humans; Men; Women; Mathematical-models; Blood-cells; Tissue-culture; Workers; Poison-gases
Contact
Eugene N. Bruce, Ph. D., Center for Biomedical Engineering, University of Kentucky, Lexington, KY 40506-0070
CAS No.
630-08-0
Publication Date
20100827
Document Type
Final Grant Report
Email Address
ebruce@uky.edu
Funding Type
Grant
Fiscal Year
2010
NTIS Accession No.
PB2012-108966
NTIS Price
A03
Identifying No.
Grant-Number-R03-OH-008651
NIOSH Division
OEP
Source Name
National Institute for Occupational Safety and Health
State
KY
Performing Organization
University of Kentucky
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