ReviewCarbon monoxide and the nervous system
Introduction
Carbon monoxide (CO) is a colorless, tasteless, odorless, and non-irritating gas formed when carbon in fuel is not burned completely. Outdoors, the largest source of CO is motor vehicle exhaust. Other sources include industrial processes, non-transportation fuel combustion, and natural sources such as wildfires. Indoors, CO can be found in tobacco smoke and can accumulate from inadequately vented stoves, furnaces, and other combustion sources. Carbon monoxide enters the bloodstream through the lungs and attaches to hemoglobin (Hb), the body's oxygen carrier, forming carboxyhemoglobin (COHb) and thereby reducing oxygen (O2) delivery to the body's organs and tissues. Equilibrium COHb levels estimated to result from increasing concentrations of CO are given in Table 1. At high concentrations, CO is poisonous. Symptoms in individuals suffering acute CO poisoning cover a wide range, depending on severity of exposure: headache, dizziness, weakness, nausea, vomiting, disorientation, confusion, collapse, and coma. Perhaps the most insidious effect of CO poisoning is the delayed development of central nervous system (CNS) impairment within 1–3 weeks, and the neurobehavioral consequences, especially in children. At lower concentrations, CNS effects include reduction in visual perception, manual dexterity, learning, driving performance, and attention level.
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Review of the literature
In this section, the arguments from the recent literature about the effect of acute exposure to CO, and its behavioral effects, will be summarized. Not only will conclusions be made and defended, but the uncertainties and their possible explanations will be discussed.
Throughout this review, it will be assumed that the mechanism by which acute CO exposure produces its effects is that of hypoxia [1], [2]. This appears to be the case for all of the other effects of acute COHb elevation. For this
Chronic effects of carbon monoxide
There are many published studies on acute experimental and accidental exposures to CO (Section 6); however, there is not enough reliable information on effects of chronic exposures to low concentrations from either controlled-human studies, ambient population-exposure studies, or from occupational studies. Further work is needed, therefore, to determine the potential for long-term exposures in the population and to develop reliable dose-response relationships for at-risk groups. This
Physiologic responses to carbon monoxide exposure
One of the possible reasons why chronic exposures to low CO concentrations may not pose as much a problem as high, acute exposure is due to physiological compensation, tolerance, or adaptation. Smokers show an adaptive response to elevated COHb levels, as evidenced by increased red blood cell volumes (through increased hemopoiesis) or reduced plasma volumes. The major source of total exposure to CO for smokers comes from active tobacco smoking. Baseline COHb concentrations in smokers average 4%
Sensitive population groups
Health effects caused by CO are most likely to occur in individuals who are physiologically stressed, either by exercise or by medical conditions that can make them more susceptible to low levels of CO. Most of the known quantitative concentration–response relationships regarding the human health effects of CO come from carefully controlled studies in healthy, predominantly male, young adults and in patients with diagnosed cardiovascular diseases (e.g. coronary artery disease). It can be
Intracellular effects of carbon monoxide
Traditional concepts for CO pathophysiology have been based on the high affinity of CO for Hb and consequent reduction of O2 delivery. Recently published information suggests the possibility for biochemical mechanisms that are not necessarily related to an impairment of oxygen delivery from elevations in COHb. Most of this research was done with cells in culture and with laboratory animals. To be relevant to human exposures from environmental contamination, it is important to note what
Physiologic role of endogenous carbon monoxide
A number of endogenously produced gases have modulation functions in biological systems (Table 3). Of these, the two diatomic gases, CO and NO, have important physiological roles in neuronal signal transduction and in the maintenance of vascular tone. The intercellular roles of these two gases are often difficult to separate.
Carbon monoxide is produced endogenously by oxidation of organic molecules, but the predominant source is from the degradation of heme. The rate-limiting enzyme for heme
Specially sensitive persons
Anyone with the inability to adequately regulate O2 supply or metabolism would seem to be specially sensitive to elevation in COHb. This has been empirically demonstrated for the onset of chest pain during exercise in angina patients. There are a number of physical conditions which impair the ability of O2 to reach the brain and thus could make persons with such an affliction more sensitive to elevated COHb. Among these are atherosclerotic lesions [80], non-insulin dependent diabetes [81], and
Disclaimer
The information in this document has been funded wholly (or in part) by the US Environmental Protection Agency. It has been subjected to review by EPA's Office of Research and Development and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
Acknowledgements
We thank S.R. Thom of the Institute for Environmental Medicine and Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA for contributions to material used in preparation of this review. We also thank J.J. McGrath of the Department of Physiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX and D.A. Otto and J.M. Davis of the US Environmental Protection Agency, Research Triangle Park, NC for their valuable comments. We extend our
References (87)
- et al.
Carbon monoxide and exposure and visual detection thresholds
Neurotoxicol Teratol
(1989) Importance of experimenter-blind procedure in neurotoxicology
Neurotoxicol Teratol
(1993)- et al.
Compensatory tracking in humans with elevated carboxyhemoglobin
Neurotoxicol Teratol
(1990) - et al.
The effect of carbon monoxide on oxygen metabolism in the brains of awake sheep
Toixicology
(1996) - et al.
Carboxyhemoglobin formation due to carbon monoxide exposure in rats
Toxicol Appl Pharmacol
(1994) - et al.
The effects of low-level carbon monoxide exposure upon evoked cortical potentials in young and elderly men
Neurotoxicol Teratol
(1988) - et al.
arbon monoxide partial pressure in tissue of different animals
Environ Res
(1970) - et al.
Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family
J Biol Chem
(2001) - et al.
Human neuroglobin, a hexacoordinate hemoglobin that reversibly binds oxygen
J Biol Chem
(2001) - et al.
Hydroxyl radical production in the brain after CO hypoxia in rats
Free Radical Biol Med
(1995)
Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat
Exp Neurol
Production of hydroxyl radical in the hippocampus after CO hypoxia or hypoxic hypoxia in the rat
Free Radical Biol Med
Nitric oxide released by platelets inhibits neutrophil B2 integrin function following acute carbon monoxide poisoning
Toxicol Appl Pharmacol
Leukocytes in carbon monoxide-mediated brain oxidative injury
Toxicol Appl Pharmacol
Carbon monoxide poisoning—a public health perspective
Toxicology
MK801 protects against carbon monoxide-induced hearing loss
Toxicol Appl Pharmacol
Cochlear protection from carbon monoxide exposure by free radical blockers in the guinea pig
Toxicol Appl Pharmacol
Protective effects of phenyl-N-tert-butylnitrone on the potentiation of noiseinduced hearing loss by carbon monoxide
Toxicol Appl Pharmacol
Carbon monoxide: an endogenous modulator of the nitric oxidecyclic GMP signaling system
Neuron
Carbon monoxide: an emerging regulator of cGMP in the brain
Mol Cell Neurosci
Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia
Neuroscience
The chemical modification of KCa channels by carbon monoxide in vascular smooth muscle cells
J Biol Chem
Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells
J Biol Chem
Influence of physiologic oscillation of estrogens on cerebral hemodynamics
J Neurol Sci
The ‘file drawer problem’ and tolerance for null results
Psychol Bull
The mini-hemoglobins in neural and body wall tissue of the nemertean worm, Cerebratulus lacteur
J Biol Chem
Behavioral effects of carbon monoxide exposure: results and mechanisms
EPA 600/P-99/001F
Introduction to environmental toxicology
Carbon monoxide
EPA 600/8-90/045F
Behavioral effects of carbon monoxide: meta analyses and extrapolations
J Appl Physiol
The effects of carbon monoxide and altitude on visual thresholds
J Aviat Med
The time course of the effects of carbon monoxide on visual thresholds
J Physiol (London)
The effects of exposure to small quantities of carbon monoxide on vision
Ann NY Acad Sci
Dark adaptation and inhalation of carbon monoxide
Acta Physiol Scand
Effects of low levels of carbon monoxide on visions of smokers and nonsmokers
Arch Environ Health
Dark adaptation of the eye during carbon monoxide exposure in smokers and nonsmokers
Aviat Space Environ Med
Behavioral impairment associated with small doses of carbon monoxide
Am J Public Health
Effects of carbon monoxide exposure on human sleep and psychomotor performance
J Appl Physiol
The effect of carbon monoxide on time perception, manual coordination, inspection and arithmetic
Effect of carbon monoxide on time perception
Acrh Environ Health
An investigation of the effects of carbon monoxide on humans in the driving task
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