Twenty intact, naturally hypercholestere-mic dogs were divided into five groups and chronically administered D-3,5,3'-triiodothy-ronine (d-T3) and L-3,5,3'-triiodothyronine (l-T3) at two levels, respectively, for 31 weeks. The administration of the drugs was divided into two periods, the first for 21 weeks, after which the dosage level for each of the four test groups was doubled for an additional 10 weeks. Plasma total cholesterol, total lipids, and phospholipids were significantly lowered by the administration at both levels of d-T3 and the higher level of l-T3. At the end of 21 and 29 weeks of thyromimetic administration, no differences in percentage of free or esterified cholesterol were observed for any of the treated groups when compared with the control groups. A battery of physiological and functional tests was performed at suitable intervals throughout the experimental period with no evidence of abnormalities due to the administration of the thyromimetic agents. The only significant functional change measured was a reduction in protein-bound-iodine levels in the clogs receiving the higher level of l-T3.
Throughout the entire experiment, all dogs remained in good health as judged by gross appearances and actions. The dogs receiving d-T3 gained less weight than did either the controls or the L-T3-treated groups, even though all animals ate isocaloric balanced diets. At post mortem, after 31 weeks of chronic thyromimetic administration, gross pathology was negative; chemical analyses of cholesterol content of aortas, adrenals, and livers indicated no significant differences. Analyses of livers for total lipids showed no significant differences, and no evidence of aortic sudanophilia was apparent in any of the experimental dogs.