With the advent of total parenteral nutrition, the nutrient absorptive role of the gastrointestinal tract during sepsis has largely been ignored. However it has recently become apparent that: 1) there is decreased mesenteric blood flow during sepsis; 2) sepsis induces ultrastructural changes in the small intestine; 3) the gut has important metabolic, immune and barrier functions in addition to that of absorption of luminal nutrients; 4) the immune, barrier and metabolic functions of the gut are impaired in sepsis; 5) these impairments in the structure and function of the gastrointestinal tract may contribute adversely to the morbidity and mortality of sepsis; 6) enteral nutrition is superior to total parenteral nutrition in preserving gut blood supply, structure and function and in promoting """"""""bowel rescue"""""""" after various types of injury, and 7) the absorptive function of the small intestine may also be impaired in sepsis. The ability of the small intestine to absorb enterally supplied nutrients is likely to be crucial to the recovery and maintenance of gut function during sepsis. This study focuses on amino acid absorption as one of the critical nutrients during sepsis. The extent and severity, of the amino acid absorptive defect in sepsis will be defined and the mechanisms and implications of this reduction in absorption will be studied.
These aims will be achieved: a) by studying the alteration in the absorption of amino acids in two experimental models of sepsis (one bacterial-induced, the other LPS-induced) using in vivo and in vitro studies; b) by studying the effect of sepsis and sepsis-induced alterations in gut amino acid absorption on amino acid incorporation into enterocyte proteins; c) by investigating the expression and rate of synthesis of enterocyte transporter proteins for proline during sepsis after preparation of a single cell suspension of enterocytes; d) by investigating the contribution of sepsis-induced macrophage activation and intestinal microvascular changes to the absorptive defect seen in sepsis.
| Gardiner, K R; Ahrendt, G M; Gardiner, R E et al. (1995) Failure of intestinal amino acid absorptive mechanisms in sepsis. J Am Coll Surg 181:431-6 |
| Gardiner, K R; Gardiner, R E; Barbul, A (1995) Reduced intestinal absorption of arginine during sepsis. Crit Care Med 23:1227-32 |
