Arginine and small intestinal atrophy in parenterally-fed neonatal piglets

Dinesh, O. Chandani (2012) Arginine and small intestinal atrophy in parenterally-fed neonatal piglets. Masters thesis, Memorial University of Newfoundland.

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Abstract

Piglets that are fed via total parenteral nutrition (TPN) experience profound gut atrophy and rapid decline in splanchnic blood flow compared to enterally-fed piglets. Sixty percent of total nutrient intake as enteral feeding is required to sustain “normal” small intestinal metabolism and morphology, which is likely not feasible with sick neonates. Whether the potential benefit of complete or partial enteral nutrition is related to single or multiple nutrients is not yet fully understood. However, the luminal presence of specific nutritive factors such as amino acids may act as trophic factors for intestinal recovery during TPN or enteral re-feeding. Arginine is a good candidate to investigate potential trophic effects as it is involved in many important metabolic pathways such as nitric oxide synthesis, ureagenesis, polyamine synthesis and protein synthesis. TPN-induced gut atrophy reduces intestinal de novo synthesis of arginine in neonates which may then limit arginine availability. We hypothesized that delivery of a high amount of dietary arginine alone into the gut could induce partial recovery from TPN-induced gut atrophy in neonatal piglets, while improving superior mesenteric artery (SMA) blood flow. We also hypothesized that enteral delivery of low amounts of arginine would result in attenuated responses compared to the high enteral arginine. Thus, our objectives were to assess the effect of route of intake and dietary concentration of arginine alone on tissue protein synthesis, SMA blood flow and gut morphology in TPN-fed neonatal Yucatan miniature piglets with small-intestinal atrophy. Twenty-four piglets (14 - 17 d old) were fed complete TPN, containing 1.0 g arginine/kg/d until study day 4 to induce atrophy, then switched to arginine-free TPN and randomized to receive a continuous intragastric infusion of either low arginine (0.6 g/kg/d) (IG-L Arg) (n = 6) or high arginine (1.6 g/kg/d) (IG-H Arg) (n = 6). A third group was randomized to receive high arginine intravenously (1.6 g/kg/d in TPN) (IV-H Arg) (n = 6). A group of sow-fed littermates (SF Reference) (n = 6) was also included. On study day 7, crypt cell proliferation and tissue specific protein synthesis rates were measured. This thesis demonstrated for the first time that the delivery of arginine alone intragastrically, irrespective of the amount provided, stimulated hepatic protein synthesis (P = 0.01) compared to intravenous delivery of arginine. SMA blood flow declined continuously during the period when all animals were receiving the same complete TPN. It further decreased following the initiation of the test diets and reached a plateau approximately 48 hours after the test diets were initiated. At steady state, SMA blood flow was significantly different among all treatment groups (P = 0.002). IV-H Arg treatment had the smallest reduction in blood flow (22% lower than baseline). The provision of high arginine enterally attenuated some of the reduction of blood flow, whereas the IG-L Arg piglets demonstrated the greatest reduction, at ~40% lower than baseline at study end. In piglets fed solely by TPN, some of the plasma indispensable amino acids were very high compared to the IG-H Arg piglets. Remarkably, the provision of only arginine into the gut resulted in a plasma profile of some of these amino acids that was very similar to sow-reared piglets. In spite of experiencing a greater amelioration of the reduction of SMA blood flow, the small intestinal morphological characteristics were not significantly improved compared to the other treatment groups. Although IG-H Arg was not as effective as IV-H Arg in sustaining SMA blood flow, morphological outcomes were not significantly worse than in the IV-H Arg piglets; indeed, the small intestine was significantly longer in the IG-H Arg piglets compared to IV-H Arg group, and all other outcomes were similar among treatment groups. These results suggest that IG delivery of arginine was likely beneficial as a trophic factor in gut-atrophied neonatal piglets.

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