Determination of the atherogenic potential of inhaled carbon monoxide.

The effects of chronic exposure to moderate levels of carbon monoxide upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies in the cockerel (young rooster). This animal model has been well characterized, especially regarding the role of environmental agents in exacerbating early stages of plaque development. Cockerels injected with subtumorigenic doses of carcinogens exhibit markedly accelerated development of aortic arteriosclerotic plaques. Inhalation of mainstream smoke from two packs of cigarettes (100 minutes/day for 16 weeks) causes small but statistically significant increases in plaque size. As is the case with many animal models of plaque development, raised fat-proliferative plaques also appear in these animals following cholesterol feeding. Carbon monoxide is a ubiquitous pollutant in urban environments, where it is derived largely from mobile sources and cigarette smoke. Exposure to chronically elevated carbon monoxide levels has been implicated in a number of health-related problems. Whether such exposure plays a role in the development of arteriosclerosis has not been determined conclusively. In the present study, three questions were posed: 1. Will inhaled carbon monoxide at levels of 50 to 200 parts per million (ppm)* (two hours/day for 16 weeks) be sufficient to augment arteriosclerotic plaque development in cockerels, in the absence of other plaque-promoting agents? 2. Will the inhalation of 100 ppm carbon monoxide (two hours/day for 16 weeks), concomitant with the feeding of low levels (0.1%) of cholesterol, yield larger plaques than those obtained with either of these agents administered alone? 3. Will inhalation of 100 ppm carbon monoxide (two hours/day for 11 or 22 weeks), by cockerels in whom plaques have already appeared, further augment plaque development? Cockerels were exposed to carefully regulated levels of carbon monoxide in stainless-steel and Plexiglas dynamic exposure chambers. The volume percentage of plaques in the wall of the abdominal aorta of each exposed and control animal was determined by a point-counting method. Chronic inhalation of carbon monoxide at levels as high as 200 ppm did not affect augmentation of arteriosclerotic plaque development. (In separate studies involving inhalation of 200 ppm carbon monoxide, carboxyhemoglobin levels 10 minutes after exposures ended were 11% to 12%.) When administered at the same time that plaque development was being promoted by cholesterol feeding, carbon monoxide had no further effect upon plaque development.(ABSTRACT TRUNCATED AT 400 WORDS)