Xicotine was administered orally in three dosage levels to female rabbits fed a. 1 per cent cholesterol, 5 per cent oil diet for 24 weeks. Serum cholesterol and phospholipid values and electrocardiograms, both with and without ergonovine stress, were obtained at eight week intervals. Gross and microaortic pathology and cardiac mieropathology were determined at the end of the experiment. Serum cholesterol and phospholipid values and aortic atherosclerosis were not affected by the addition of nicotine. Mortality, the incidence of positive ergonovine stress tests, myocardial necrosis and fatty metamorphosis, and peripheral vascular changes were increased. A dose-response relationship could not be established for nicotine. I T HAS been reported1 ' -that nicotine increases the plasma cholesterol levels of male rabbits on a cholesterol-fortified diet. The purpose of this study was to determine the effect of graded doses of nicotine plus a high cholesterol-oil diet on atherosclerosis using the following criteria: serum cholesterol and phospholipid levels, electrocardiographic changes both before and after ergonovine stress, and gross and micropathology of the heart and contiguous vessels. METHODSSix groups of 12 albino, Xew Zealand, six-week old, female rabbits per group were established. AH animals weighed between 1.7 and 2.1 Kg. Group 1 received the stock diet of Purina rabbit chow and water ad libitum. For group 2 the food was impregnated with 1 per cent cholesterol and 5 per cent cottonseed oil. Group 3 was fed the stock diet plus the human nicotine equivalent by body weight of two packs of cigarettes daily in the drinking water. This dose is based upon the report that 4 /ig. of nicotine per os produces the same psychic effects as one cigarette in the chronic smoker. Supported by a grant from the Tobacco Industry Research Committee.We are indebted to 51>. J. W. Lansdowne, Eli Lilly and Company, for the ergonovine maleate used in this study.Received for publication September 17, 1958. 256 adult human weighl the daily two pack equivalent is 2.28 nig. nicotine/Kg, body weight, the one-half pack equivalent is 0.57 ing./Kg., and the one-eighth pack equivalent is 0.142 mg./Kg. Groups 4, 5, and 6 received the group 2 diet and one-eighth, one-half, and two pack equivalents of nicotine respectively. In order to reduce the possibility of acute effects from the nicotine, the dose was gradually increased in order to produce tolerance. Each group was started with onetwelfth the calculated daily dose for the first three days. This amount was increased by a similar quantity every three days until the full dose was being administered on the thirty-sixth day.Determinations of body weight, serum cholesterol, and phospholipid and electrocardiographsactivity both with and without ergonovine were made initially and every eight weeks thereafter for a period of 24 weeks.Electrocardiography was performed with an Edin C. C.-D. C. amplifier and a Brush Model liL-201 oscillograph at a paper speed of 25 mm./ second. The usual limb leads ...

No abstract

No abstract

No abstract