Carbon Monoxide and Atherosclerosis

I-El HEALTH EFFECTS INSTITUTE The Health Effects Institute, established in 1980, is an independent and unbiased source of information on the health effects of motor vehicle emissions. HEI studies all major pollutants, including regulated pollutants (such as carbon monoxide, ozone, nitrogen dioxide, and particulate materials), and unregulated pollutants (such as diesel engine exhaust, methanol, and aldehydes). To date, HEI has sup ported more than 120 projects at institutions in North America and Europe. HEI receives half its funds from the Environmental Protection Agency and half from 28 manufacturers and marketers of motor vehicles and engines in the U.S. However, the Institute exercises complete autonomy in setting its research priori ties and in disbursing its funds. An independent Board of Directors governs the Institute. The Research Committee and the Review Committee serve complemen tary scientific purposes and draw distinguished scientists as members. The results of REI-funded studies are made available as Research Reports, which contain both the investigator's report and the Review Committee's evaluation of the work's scien tific and regulatory relevance. Synopsis of Research Report Number 57 Carbon Monoxide and Atherosclerosis Background Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehicles, industrial processes, and poorly ventilated combustion sources. Despite reductions in ambient carbon monoxide concentrations during the last decade, 22 million people live in areas of the United States that exceed the National Ambient Air Quality Standard for carbon monoxide (9 parts per million [ppm] averaged over eight hours and 3 5 ppm averaged over one hour). Inhaling carbon monoxide is dangerous because the gas binds to hemoglobin in red blood cells to form carboxyhemoglobin. This displaces oxygen and reduces hemoglobin's ability to deliver oxygen to body tissues. If tissues are deprived of oxygen, transient or permanent damage can occur, especially in those organs that demand high oxygen delivery, such as the brain and heart. The lethal consequences of exposure to high concentrations of carbon monoxide are well known. There is also concern that exposure to low levels of carbon monoxide may produce adverse effects, especially on the cardiovascular system. Carbon monoxide could manifest its toxic effects on the heart and blood vessels in two ways, either by causing acute, short-term effects on oxygen delivery or by contributing to the development of cardioyascular diseases such as atherosclerosis. Atherosclerosis is a progressive disease characterized by thickening of the arteries and a buildup of deposits of fat, cholesterol, cells, and connective tissue in the inner lining of the blood vessels. These deposits, called plaques, can partially or totally block the flow of blood through the artery. The known risk factors for atherosclerosis are family history of the disease,· diet, high blood pressure, and cigarette smoking. (Mainstream and sidestream cigarette smoke have extremely high levels of carbon monoxide [400 to 1,000 ppm]). It is important to know whether chronic exposure to ambient levels of carbon monoxide is also a risk factor for developing atherosclerosis because this disease is the leading contributor to deaths by heart attack and stroke in the United States. Approach Birds are appropriate animal models for studying atherosclerosis because some species develop spontaneous atherosclerotic plaques that resemble those in humans. Dr. Arthur Penn and his colleagues previously had shown that the development of atherosclerotic plaques in cockerels (young roosters) was enhanced when the birds were exposed to cigarette smoke or treated with agents that stimulate cell proliferation, such as chemical carcinogens. In the study described here, Dr. Penn exposed cockerels to either air or defined levels of carbon monoxide (50 to 200 ppm) for 16 weeks and measured the size of the atherosclerotic plaques in the abdominal aorta. He also examined whether carbon monoxide promoted atherosclerosis when the birds were fed a low cholesterol (0.1 %) diet and exposed to carbon monoxide (100 ppm) at the same time. Finally, he determined whether carbon monoxide exposure altered the development of preexisting plaques. Results In this study, none of the carbon monoxide exposures, either alone, or in combination with a low cholesterol diet, had an effect on the rate of development or the regression of atherosclerotic plaques in cockerels. Reliable blood carboxyhemoglobin measurements were not obtained. Consequently, there was no biomarker · linking external carbon monoxide exposure concentrations and internal dose. Because birds and mammals differ in their uptake and elimination of carbon monoxide, it is possible that the actual carbon monoxide body burden was relatively minimal and not comparable to human exposures. Considering this uncertainty, the results of this study do not provide a definitive answer to the question of whether exposure to carbon monoxide is a risk factor for atherosclerosis. The evidence favoring such a role at ambient carbon monoxide· levels is not strong; however, because of the importance of the problem, the issue warrants further evaluation. This Statement is a summary, prepared by the Health Effects Institute (REI) and approved by the Board of Directors, of a research project sponsored by REI from 1986 to 1988. This study was conducted by Dr. Arthur Penn at New Yark University Medical Center. The complete report (Determination of the Atherogenic Potential of Inhaled Carbon Monoxide, Research Report Number 57) can be obtained from the Health Effects Institute, 141 Portland Street, Suite 7300, Cambridge, MA 02139 (Telephone: 617-621-0266). The Research Report contains both the detailed Investigator's Report and a Commentary on the study prepared by the Institute's Health Review Committee. Please see reverse side for Table of Contents. FENN 57 Deter i ti n of the lE[ Ather enic P te ti I of lnh led C r n M oxide Research Report Number 57 Table of Contents Investigators' Arthur Penn Report Abstract Results Chamber Carbon Monoxide Measurements Introduction Carbon Monoxide Dose Response Objectives and Rationale Carbon Monoxide as a Coatherogen Materials and Methods Role of Carbon Monoxide in Plaque Animal Care Augmentation Treatment Regimens Carboxyhemoglobin Levels Plaque Morphometry Discussion Methodology for Analysis of Carbon Monoxide in Whole Blood Samples Conclusions Cholesterol Determinations Appendix A. Gas Chromatograph Modified for Carbon Monoxide Analysis Data Analysis Commentary Health Review Committee Introduction Technical Evaluation Attainment of Study Objectives Regulatory Background Methods Scientific Background Study Design Carbon Monoxide Statistical Methods Cardiovascular Effects of Carbon Monoxide Results and Interpretation Justification for the Study Implications for Future Research Objectives Conclusions Study Design @ Recycled Paper 1-£[ Statement Synopsis of Research Report Number 57 Carbon Monoxide and Atherosclerosis BACKGROUND Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehi cles, industrial processes, and poorly ventilated combustion sources. Despite reductions in ambient carbon monoxide concentrations during the last decade, 22 million people live in areas of the United States that ex ceed the National Ambient Air Quality Standard for carbon monoxide (9 parts per million [ppm] averaged over eight hours and 35 ppm averaged over one hour). Inhaling carbon monoxide is dangerous because the gas binds to hemoglobin in red blood cells to form carboxyhemoglobin. This displaces oxygen and reduces hemoglobin's ability to deliver oxygen to body tissues. If tissues are deprived of oxygen, transient or permanent damage can occur, especially in those organs that demand high oxygen delivery, such as the brain and heart. The lethal consequences of exposure to high concentrations of carbon monoxide are well known. There is also concern that exposure to low levels of carbon monoxide may produce adverse effects, especially on the cardiovascular system. Carbon monoxide could manifest its toxic effects on the heart and blood vessels in two ways, either by causing acute, short-term effects on oxygen delivery or by contributing to the development of cardiovascular diseases such as atherosclerosis. Atherosclerosis is a progressive disease characterized by thickening of the arteries and a buildup of deposits of fat, cholesterol, cells, and connective tissue in the inner lining of the blood vessels. These deposits, called plaques, can partially or totally block the flow of blood through the artery. The known risk factors for atherosclerosis are family history of the disease, diet, high blood pressure, and cigarette smok ing. (Mainstream and side stream cigarette smoke have extremely high levels of carbon monoxide [400 to 1,000 ppm]). It is important to know whether chronic exposure to ambient levels of carbon monoxide is also a risk factor for developing atherosclerosis because this disease is the leading contributor to deaths by heart attack and stroke in the United States. APPROACH Birds are appropriate animal models for studying atherosclerosis because some species develop spontaneous atherosclerotic plaques that resemble those in humans. Dr. Arthur Penn and his colleagues previously had shown that the development of atherosclerotic plaques in cockerels (young roosters) was enhanced when

Load more