Experimental Vascular Disease in Rats Produced by Multiple Depletions of Vitamin A. ∗

The pathology of chronic vitamin deficiency is usually studied in laboratory animals which have been subjected to a partial deficiency over a long period of time. This dietary method has been considered to represent the closest analogy to the course of the human disease. 1 The present experiment was designed to effect pathologic changes in the rat by successive and complete depletions of vitamin A rather than by sustained and partial withdrawal of the vitamin. To obtain this end, multiple avitaminotic episodes of varied severity were interspersed with periods of relative recovery.

Procedure. Twenty-four pairs of rats, litter-mates of the same sex and ranging in weight from 50 to 100 g, were given a basal ration† deficient in vitamin A and supplemented only in the control rat of each pair with 3 drops of carotene in oil.§

Successive depletions in each pathologic rat were usually terminated by the oral administration of carotene. This vitamin was provided only until the fall in weight was definitely checked. Diarrhea sometimes made necessary the subcutaneous injection of 0.5 cc of cod liver oil for a brief period. Response to the resumption of vitamin therapy varied in each animal with each depletion, due apparently to variations in degree of the underlying pathology, chiefly of the renal or of the respiratory tract. Two or 3 depletions were obtainable in each rat during an experimental period ranging from 127 to 238 days. For histologic study of the arterial system, the tissues following autopsy were fixed in Bouin's solution, embedded in paraffin and stained with hematoxylin-eosin or v. Kossa's method for calcium.

Vascular Pathology. All but 3 of the 24 multiply depleted rats showed some degree of vascular injury.