Serious injury causes a number of metabolic and nutritional changes, impaired healing (established in experimental animals), and decreases in host defense mechanisms leading, all too frequently, to increased morbidity and mortality. These factors are all closely interrelated. Our overall hypothesis is that supplemental vitamin A and B carotene will modulate each of them in ways which will lessen their impact on one another and mitigate the resultant physiological and clinical consequences, but this remains to be established. Specifically, we hypothesize that (1) there are alterations in vitamin A metabolism after injury which result in an increased requirement for vitamin A; (2) supplemental vitamin A will affect certain of the key hormonal and other metabolic reactions to injury in ways which will benefit the injured individual, e.g., by lessening nutritional derangements and improving wound healing; (3) supplemental vitamin A improves wound healing by affecting fibroblasts directly as manifested by changes in growth characteristics and function, resulting in increased rates of accumulation of reparative collagen and wound remodelling as a consequence of alterations in the balance of collagen synthesis and collagenolysis; this is in addition to the demonstrated effect of an increase in the inflammatory response to wounding, notably an increase in the influx and function of monocytes and macrophages by supplemental vitamin A; (4) supplemental vitamin A will modulate many of the impaired host defense factors, immunologic (humoral and cell-mediated) and non-specific cellular, which follow serious injury and thereby increase host resistance to infection. a series of comprehensive in vitro (tissue culture), animal, and clinical studies will be carried out to test these hypotheses. Biochemical, physiologic, immunologic, microbiologic, hematologic, and histological methods will be used. Wound healing in the patients will be studied by following the healing of small experimental wounds. Included will be studies to determine the effects of supplemental A carotene, the precursor of vitamin A, because a) B carotene has minimal toxicity even when given in very large doses and b) it may have salutary effects independent of its conversion to vitamin A. The long term objective of these studies is to determine whether supplemental vitamin A and B carotene will, as postulated, lower morbidity, speed convalescence and decrease mortality of seriously injured patients.
