Provision of phosphorylatable substrate during hypoxia decreases jejunal barrier function

OBJECTIVES: There is an emerging consensus that early enteral nutrition benefits the high-risk surgical patient. However, in patients with inadequate gastrointestinal perfusion, food in the intestine may increase the oxygen demand beyond that which can be satisfied by the available delivery, potentially leading to intestinal malfunction. The effect of metabolic substrate on gastrointestinal function during various oxygenation states was investigated. METHODS: Jejunal samples obtained from 32 male Sprague-Dawley rats (263 ± Q15 g) were stripped of the muscularis, mounted in modified Ussing chambers, and randomized to be incubated in media equilibrated with one of four gas mixtures (95%, 75%, 50%, and 25% oxygen). After equilibration, fluorescent probes (4400 and 17 200 molecular weight [MW]) were added to the incubation media on the mucosal side. The rate of probe accumulation on the serosal side was determined before and after the addition of one of four substrates to the mucosal medium: mannitol (an osmotic control), glucose (which is transported, phosphorylated, and metabolized), 2-deoxyglucose (a glucose analog that is transported and phosphorylated but not metabolized), or 3-O-methylglucose (a glucose analog that is transported but not phosphorylated or metabolized). RESULTS: Lumenal glucose, 2-deoxyglucose, and 3-O-methylglucose increased permeation of the 4400-MW probe at all oxygen levels, whereas mannitol did not alter permeation in the 95% and 75% oxygen groups. Lumenal glucose increased (P < 0.05) the permeation rate of the 17 200-MW probe at all oxygen levels, whereas 2-deoxyglucose and 3-O-methylglucose did not increase the permeation rate of the 17 200-MW probe until oxygen was lowered to 75% and 50%, respectively. Regardless of substrate treatment, jejunal permeation of the 4400-MW (P < 0.001) and 17 200-MW (P < 0.05) probes increased in the 25% and 50% oxygen groups compared with the 75% and 95% oxygen groups. CONCLUSIONS: These initial results suggest that the provision of lumenal nutrients exacerbates the loss of gastrointestinal barrier function during hypoxia. Although the early provision of nutrients is an important intervention in acutely injured patients, care must be taken to ensure that gastrointestinal perfusion is adequate to allow substrate metabolism and prevent further compromise in gastrointestinal function.