Intravenous glutamine or limited enteral feedings in piglets: amelioration of small intestinal disuse atrophy.

In hospitalized patients, a multitude of factors including loss of luminal trophic factors, altered splanchnic blood flow and nutritional deprivation lead to gastrointestinal mucosal atrophy. Clinical orders of nothing per os (NPO) or “bowel rest” cause intestinal atrophy, which leads to abnormal enteric flora with bacterial, endotoxin or cytokine translocation, altered host immune function and sepsis (Barber et al.1991, Zaloga 1994). The prevention or limitation of intestinal atrophy during small bowel disuse or “rest” would have clinical significance if fewer hospital days and lower infection rates resulted. Glutamine is the preferred respiratory fuel for enterocytes; administration of 2% glutamine solutions is known to be beneficial in the short term. However, glutamine is more like a conditionally essential amino acid, necessary only during recovery to stimulate DNA synthesis and increase mucosal mass (Lacey and Wilmore 1990). Glutamine administered intravenously (IV) long term to animals with intestinal atrophy has not been adequately investigated in clinically relevant species. Enteral feedings are also known to be beneficial in preventing intestinal disuse. Data in critically injured patients suggest that enteral nutrition had a positive effect on intestinal immune function and leads to decreased infectious morbidity and reduced hospital stay (Heyland et al.1993). Possible advantages of feeding small volumes enterally during prolonged periods of small bowel “rest” therapy have also not been investigated, but such feeding is quite possible in most hospitalized cases as a means of minimizing intestinal atrophy. The objective of this study was to compare the small intestinal response to intravenous glutamine vs. intermittent small volume enteral feedings, administered for .1 wk as a means of preventing intestinal atrophy. The piglet has become the preferred small intestinal research model because of the homology among the swine, human, canine, feline and equine small bowels. The small intestines of the dog, cat, pig and foal are very similar in morphology and physiology through the first year of life, and the atrophic response to NPO also appears to be similar. The information derived from a swine research model of small intestinal atrophy is, therefore, relevant to the small bowel changes after disuse in dogs, cats and foals. Materials and methods. Five litters of Hampshire 3 Duroc piglets were selected on the basis of body weight (BW) (1.8–2.7 kg) at 4 d of age. Four litter mates were randomly assigned to one of the following four treatments: 1) 100% enterally fed sow’s milk replacer (SMR); 2) total parenteral nutrition (TPN); 3) TPN with 1.7% (wt/v) glutamine (GLN); or 4) 90% of total energy as TPN plus 10% enterally as SMR (PEN). The TPN treatment served as a negative control, whereas SMR served as a positive control. Because of logistical limitations, four litter mates (1 piglet/treatment) completed the 28-d feeding trial at a time. Piglets were maintained in accordance with the Animal Care Committee guidelines at the Johns Hopkins Medical Institutions and the Committee on Care and Use of Laboratory Animals from the Institute of Laboratory Animal Resources. Nutritional treatments. All piglets suckled sow’s colostrum/milk until delivered to the laboratory at 4 d of age; they also received an iron dextran injection (100 mg intramuscularly) at 3 and 10 d of age. Catheters (1.0 mm i.d., 2.1 mm o.d., 91 cm) of medical grade silastic tubing (Dow Corning, Midland, MI) were surgically placed in the left and right external jugular veins of all piglets. The catheter tips were inserted into the cranial vena cava; the proximal end of the catheter was tunneled to the dorsum, passing cranially to the shoulder and exiting 5–10 cm posterior to the ear. One catheter was used for parenteral administration, and the second was used for blood sampling. Weekly blood samples were 1 Presented as part of the Waltham International Symposium on Pet Nutrition and Health in the 21st Century, Orlando, FL, May 26–29, 1997. Guest editors for the symposium publication were Ivan Burger, Waltham Centre for Pet Nutrition, Leicestershire, UK and D’Ann Finley, University of California, Davis. 2 Supported by National Institutes of Health grant HD21093. 3 To whom correspondence should be addressed at Angell Memorial Animal Hospital, Boston, MA 02130. 4 Current address: Fort Dodge Animal Health, Princeton, NJ. 5 Current address: Rainbow Babies and Childrens Hospital, Cleveland, OH. 6 Abbreviations used: BW, body weight; GLN, glutamine; IV, intravenous; NPO, nothing per os; PEN, 90% of total energy as TPN plus 10% enterally as SMR; SB, small bowel; SMR, sow’s milk replacer; TPN, total parenteral nutrition.