The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers. KEY WORDSpregnancy placenta carbon monoxide nicotine tissue hypoxia vascular injury• Clearly, a close connection exists between tobacco smoking and development of arterial diseases, especially coronary heart disease and peripheral arterial disease (1). The question is how does tobacco smoke provoke arterial damage. Evidence accumulated during the last decade indicates that the carbon monoxide in tobacco smoke is harmful to the arterial wall (2). Exposure to low doses of carbon monoxide accelerates atherogenesis in cholesterol-fed animals (3-5) and produces significant ultrastructural changes in the aortic and the coronary endothelium of rabbits and primates that are indistinguishable from early atherosclerosis (6, 7). For obvious reasons similar exposure studies and subsequent vascular biopsies cannot be performed in humans. Moreover, a comparison of vascular biopsy studies in human smokers and nonsmokers has not been published to date. As a possible model for evaluating the vascular damage provoked by tobacco smoking in humans, the umbilical artery of babies of smoking and nonsmoking mothers was used for ultrastructural studies in the present paper. Methods PATIENTSPregnant women admitted to the Department of Obstetrics and Gynecology at Rigshospitalet were selected for the study. All patients were examined by the same investigator, and each subject completed a questionnaire on smoking habits before and during pregnancy. Twenty-eight patients took part in the study, 13 smokers and 15 nonsmokers. All smokers were inhaling cigarette smokers. One subject smoked 40-60 cigarettes daily.Women suffering from hypertension, diabetes, and other diseases and those with Rh negative blood types were not used in this study. The patients chosen for the study were normal before and during the pregnancy: all laboratory investigations (hemoglobin, blood, sugar, etc.) including urinary analyses for sugar, protein, and estriol were normal. Therefore, the only ...

The placenta was chosen as a possible model for evaluating the vascular injury and tissue injury provoked by tobacco smoking in the human body. Full term placentas from 4 smokers and 3 non-smokers were studied in the transmission electron microscope. Pronounced changes were found in the group of smokers. The characteristic findings were broadening of the basement membrane of the placental villus, increase in collagen content of the villus, decrease in vascularisation and intimal changes in the villous capillaries and arterioles, with pronounced intimal oedema. Since similar changes have been reported previously from human umbilical arteries, and since these changes also can be induced in animal arteries by exposure to carbon monoxide or perfusion with nicotine, this study supports the concept that tobacco smoking is harmful to the human vascular system and tissues.

Summary The ultrastructure of placental villi from 10 heavy smokers (10≥cigarettes per day) was compared with that of 16 nonsmokers (never smoked). Thickening of the basement membrane and increase in collagen content of the villous stroma was found. The fetal capillaries were fewer in number and with decreased lumen either due to oedema or contraction of the endothelial cells. All cells, both in the fetal capillaries as well as syncytiotrophoblast and cytotrophoblast contained large amounts of filaments and fibrillae possibly capable of cell contraction. Thus a result of these findings might be a decreased placental flow in smokers.

Smokers are exposed to a large number of genotoxic compounds that react with DNA to form covalently bound carcinogen-DNA adducts after metabolic conversion to their biological active form. Using the P32-postlabeling techniques, tobacco smoke related carcinogen--DNA adducts have been demonstrated in DNA isolated from human placenta and umbilical cord vein and artery obtained from 11 nonsmoking and 8 smoking normal healthy women and foetuses. The adduct level was significantly higher in tissues from smokers than from nonsmokers (P = 0.021), when all tissues were combined. Furthermore, the total adduct level was higher in maternal tissue than the level in fetal tissues (P = 0.030). The adduct level in umbilical cord vein DNA was significantly lower than in placenta, and marginally lower than in umbilical cord artery from the same donor. This suggests that the foetus can metabolise some of the genotoxic compounds found in tobacco smoke to DNA-binding metabolites. The presence of DNA adducts in foetal tissues is indicative of potential genomic damage, that may result in an increased risk for the development of serious diseases, like cancer in childhood or later during the life span of the individual.