EFFECTS OF CARBON MONOXIDE EXPOSURE ON THE ARTERIAL WALLS

During discussions on the relation between tobacco smoking and the development of arteriosclerosis the attention has for many years been focused on the influence of nicotine on the cardiovascular system, whereas the CO in tobacco smoke has not been considered to have any pathogenetic importance. In animal experiments, moreover, it has not been possible to prove an atherogenic effect of nicotine by itself. In our Department at Rigshospitalet the finding of high concentrations of carboxyhemoglobin, in especially young smokers with obliterating arterial diseases, led to the initiation of experimental animal investigations on the significance of CO exposure in the development of arteriosclerosis. An injurious effect on the vascular system by even small concentrations of carboxyhemoglobin maintained for some weeks was demonstrated, thereby underlining the definite possibility of CO in tobacco smoke as an increased risk for smokers to develop arteriosclerosis, a possibility which, so far, had been disregarded. The investigations were initiated by the findings of oxyhemoglobin dissociation curves that were displaced to the left in many young smokers with peripheral or cardial arteriosclerotic Subsequent investigation^^. ^ showed that the displacements were caused by high concentrations of carboxyhemoglobin in the blood, even after moderate smoking, often as high as 10 to 15 and up to 20%? Similar high values have also been reported by other investigator^. ^ This led to animal experiments for evaluating the possibility of a connection between either the increased oxygen affinity or the high carboxyhemoglobin concentration and the vascular injuries. We thus constructed airtight chambers in which we placed rabbit cages, through which we could introduce various gas mixtures. These were made by mixing atmospheric air with CO, oxygen, and nitrogen, respectively. For the various series we have used different techniques described in detail else~ h e r e . 6 ~ A grouping of some of the main results is shown in TABLE 1, in which it seems that the cholesterol content of aorta in cholesterol-fed animals continuously exposed to CO for ten weeks (15% carboxyhemoglobin for eight weeks, 30% the last two weeks), on an average, was 2.5 times higher than in the control animals, which had not been exposed to CO, but which were fed cholesterol. By intermittent exposure, eight hours a day for ten weeks, to a CO gas mixture leading to 20% carboxyhemoglobin concentration, the experimental animals obtained as much as five times higher aortic cholesterol concentrations than did the control animals. In another series of experiments we exposed animals to 10% oxygen for eight weeks and obtained 3.5 times higher cholesterol concentrations in aorta walls from the experimental group than from the control group. If, on the other hand, the breathing air contained 28% oxygen, the content of cholesterol dropped to approximately half the concentration of the control animals. Macroscopically as well as microscopically there was no difference between the arterial lesions in animals exposed to CO and the animals exposed to hypoxia. Macroscopically it was easy to distinguish between the aortas from the exposed animals and from the control animals by the number and size of plaques. Similarly, the microscopic changes were more pronounced in the experimental animals, characterized by a marked lipid accumulation in intima and subintima. Also, without