BENEFICIAL-EFFECTS OF PRETREATMENT WITH VITAMIN-A ON CARDIAC AND PULMONARY FUNCTIONS IN ENDOTOXAEMIC PIGS

Background: Septic shock is associated with high mortality despite the development of new antibiotics. Since Vitamin A has an immunomodulati ng ability and is able to lower the concentrations of endotoxin and so me cytokines, we decided to study whether supplementation with vitamin A may have a beneficial effect in experimental endotoxaemia. Methods: A porcine model was used, in which normally bred (i.e., not vitamin A depleted) animals were anaesthetised, monitored and injected intramus cularly with a non-toxic dose of vitamin A (230IU . kg(-1)) (n=9) or t he corresponding volume of vehicle (n=9) I hour before an infusion of purified E. coli endotoxin was given in a dose of 10 mu g . kg(-1). h( -1) over 6 hours. Another 3 pigs also injected with vitamin A, but not endotoxin, served as controls. Results: Vitamin A- and endotoxin-inje cted pigs were significantly less affected in several circulatory and respiratory variables as compared to vehicle- and endotoxin-injected a nimals (e.g., blood pressure; heart rate; cardiac index; pulmonary cap illary wedge pressure; left and right ventricular stroke work indices; pH; base excess; oxygen delivery; and oxygen extraction). Vitamin A d id not per se significantly affect these variables. Hb increased signi ficantly in the vehicle group, indicating a more pronounced capillary permeability. Urinary output or fluid supply did not differ between th e groups. Myocardial production of metabolites of prostacyclin or thro mboxane A, did not differ between the groups. Conclusion: Pre-treatmen t with vitamin A had a beneficial effect on several variables, such as oxygen delivery and metabolic acidosis in the endotoxaemic pig. Impro vement of these variables is associated with increased survival in sep tic shock and may indicate reduced tissue hypoxia. Thus, vitamin A may turn out to be useful as a prophylactic agent in conditions where sep tic shock is apt to occur.