Luminal nutrients exacerbate intestinal hypoxia in the hypoperfused jejunum.
BACKGROUND
Provision of enteral nutrients shortly after traumatic injury has become the preferred method of nutrition support provided to patients. However, traumatic shock results in splanchnic hypoperfusion, which may cause persistent intestinal hypoxia. This study tested the hypothesis that delivery of enteral nutrients to the hypoperfused jejunum increases oxidative demand beyond that available, thereby exacerbating intestinal hypoxia.


METHODS
Wistar-Furth rats (186+/-4 g; n = 24) were randomized to receive intestinal hypoxia (superior mesenteric artery occlusion) or serve as normoxic controls (sham laparotomy). Within the jejunum of each rat, 4 6-cm loops were randomized to receive luminal perfusions with 1 of 4 substrates: mannitol (an osmotic control); glucose (undergoes active transport via the sodium-glucose co-transporter [SGLT-1] and is metabolized); 3-o-methylglucose (3-o-mg; uses SGLT-1 but is not metabolized); or fructose (does not use SGLT-1 but is metabolized). After in situ perfusions, jejunal tissue was removed for analysis of nutrient transport and barrier function in modified Ussing chambers. Tissue homogenate was used to determine concentration of ATP, lactate, pyruvate, and protein. Also, jejunal tissue was stained with hematoxylin and eosin for qualitative analysis of ischemia and necrosis.


RESULTS
Transmural resistance was lower (p < .001) in the hypoxia groups, irrespective of substrate, indicating increased mucosal permeability. When compared with the normoxic controls, glucose transport was impaired (p < .001) in the hypoxic groups; however, glutamine transport was unaffected. The degree of intestinal hypoxia, assessed by jejunal lactate concentration, was higher (p < .001) in the glucose and fructose groups, than the control mannitol and 3-o-mg groups.


CONCLUSIONS
The observation that 3-o-mg did not differ from the mannitol control indicates that SGLT-1 activation alone does not exacerbate hypoxia. Rather, these results indicate that provision of metabolizable nutrients to the hypoperfused intestine exacerbate hypoxia and potentially lead to intestinal ischemia. Although early enteral nutrition is an important intervention after trauma, care must be taken to ensure intestinal perfusion is adequate to allow for nutrient metabolism and prevent further compromise.
Kles
K A
KA
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 61801, USA.
Wallig
M A
MA
Tappenden
K A
KA
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004750:Enteral Nutrition / Q000009:adverse effects*; D005260:Female; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000209:etiology* / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology; D008353:Mannitol / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010477:Perfusion; D010539:Permeability; D051381:Rats; D011920:Rats, Inbred WF; D051269:Sodium-Glucose Transporter 1
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D019325:3-O-Methylglucose; D005632:Fructose; D008353:Mannitol; D005947:Glucose