Beneficial effects of pre-treatment with vitamin A on cardiac and pulmonary functions in endotoxaemic pigs

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Abstract
Background: Septic shock is associated with high mortality despite the development of new antibiotics. Since Vitamin A has an immunomodulating ability and is able to lower the concentrations of endotoxin and some 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 intramuscularly with a non‐toxic dose of vitamin A (230IU·kg‐1) (n=9) or the corresponding volume of vehicle (n=9) 1 hour before an infusion of purified E. coli endotoxin was given in a dose of 10 μg· 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‐injected pigs were significantly less affected in several circulatory and respiratory variables as compared to vehicle‐ and endotoxin‐injected animals (e.g., blood pressure; heart rate; cardiac index; pulmonary capillary wedge pressure; left and right ventricular stroke work indices; pH; base excess; oxygen delivery; and oxygen extraction). Vitamin A did not per se significantly affect these variables. Hb increased significantly in the vehicle group, indicating a more pronounced capillary permeability. Urinary output or fluid supply did not differ between the groups. Myocardial production of metabolites of prostacyclin or thromboxane A2 did not differ between the groups. Conclusion: Pre‐treatment with vitamin A had a beneficial effect on several variables, such as oxygen delivery and metabolic acidosis in the endotoxaemic pig. Improvement of these variables is associated with increased survival in septic shock and may indicate reduced tissue hypoxia. Thus, vitamin A may turn out to be useful as a prophylactic agent in conditions where septic shock is apt to occur.