CARDIOVASCULAR LESIONS IN SPRAGUE‐DAWLEY RATS INDUCED BY LONG‐TERM TREATMENT WITH CAFFEINE

Male Sprague‐Dawley rats were treated with phenacetin, phenazone or caffeine in the diet or with combinations of these chemicals for up to 117 weeks. Twenty of twenty‐eight rats receiving caffeine only developed moderate to severe myocardial fibrosis compared with five control rats, in spite of the fact that the control rats had a sixteen weeks longer average life‐span. Four caffeine‐treated rats had histologic evidence of acute myocardial infarction which was not found in any of the other rats. Forty percent of the rats treated with caffeine only or with caffeine and phenacetin in combination were found to have periarteritis nodosa‐like lesions in the mesenteric vessels. Seventy‐nine percent of the rats treated with caffeine only and 52 percent of those treated with caffeine and phenacetin died from cardiovascular disease, compared with 17 percent among the control rats. Thus, long‐term administration of caffeine to Sprague‐Dawley rats is associated with markedly reduced life‐span due to cardiovascular disease.