|Niinikoski, Harri - BAYLOR COLL MEDICINE|
|Stoll, Barbara - BAYLOR COLL MEDICINE|
|Guan, Xinfu - BAYLOR COLL MEDICINE|
|Kansagra, Ketan - BAYLOR COLL MEDICINE|
|Lambert, Barry - BAYLOR COLL MEDICINE|
|Hartmann, Bolette - UNIV COPENHAGEN DENMARK|
|Stephens, J. - BAYLOR COLL MEDICINE|
|Holst, J. - UNIV COPENHAGEN DENMARK|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 11, 2004
Publication Date: June 1, 2004
Citation: Niinikoski, H., Stoll, B., Guan, X., Kansagra, K., Lambert, B.D., Hartmann, B., Holst, J.J., Burrin, D.G. 2004. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. Journal of Nutrition. 134(6):1467-1474. Interpretive Summary: Babies that are born prematurely and are underdeveloped sometimes have to be fed other than by mouth, since they can't digest their food properly. These babies have to be fed by a method called total parenteral nutrition (TPN), which means that they are fed fluid through tubes that detour around the normal digestive system. Doctors prefer not to keep the babies on TPN too long because it is vital to get all the newborn organs working and developing, catching up to appropriate growth rates, since diminished intestinal function has been found in TPN-fed babies. The question is, how long is too long? And what, exactly, causes the mucosal withering, or atrophy, associated with TPN? We wanted to find out precisely how fast TPN-induced mucosal atrophy occurs in newborns, and whether that time is associated with changes in intestinal blood flow and tissue metabolism, which we suspected. Using newborn pigs as models for newborn humans, we set up three study groups. One group got continuous, normal formula feeding; the second got TPN for 24 hours; and the third got TPN for 48 hours. We measured blood flow, protein synthesis rates, and other features. Intestinal mucosal atrophy was evident after just 24 hours of TPN. During the 48-hour period, mucosal atrophy occurred faster and to a greater degree in the proximal than the distal small intestine. The loss of mucosal protein and DNA mass after 48 hours of TPN was accompanied by a reduction in protein synthesis and cell proliferation. Within hours, TPN suppressed portal blood flow and jejunal mucosal blood flow, preceding the mucosal atrophy. Our results are the first to reveal a potential link between blood flow and TPN-induced mucosal atrophy. We also showed that this atrophy occurs surprisingly quickly, within just 24 hours of TPN, whereas previous studies have only shown it to happen within 3 days. Thus, we showed that the speedy onset of small intestinal atrophy is associated with reduced portal blood flow in TPN-fed neonatal piglets. This extremely important study could lead to new strategies, either nutritional or therapeutic, to maintain blood flow and enhance intestinal function in newborn babies.
Technical Abstract: Our aim was to determine the speed of onset of total parenteral nutrition (TPN)-induced mucosal atrophy, and whether this is associated with changes in intestinal blood flow and tissue metabolism in neonatal piglets. Piglets were implanted with jugular venous and duodenal catheters and a portal vein blood flow probe. At 3 wk of age, piglets were randomly assigned to receive continuous enteral formula feeding (n=8), TPN for 24 h (n=9), or TPN for 48 h (n=8). Blood flow was recorded continuously and piglets were given an intravenous bolus of BrdU and 13C-phenylalanine to measure crypt cell proliferation and protein synthesis, respectively. Compared to enteral feeding, portal blood flow decreased (P < 0.01) 30%, to near fasting levels, after 7 h of TPN and remained low during the 48 h of TPN. Jejunal inducible NOS (iNOS) activity was also decreased (P < 0.05) by 40% after 24 h of TPN. Small intestinal weight and jejunal villus height were lower (P < 0.01) after 24 h and 48 h in TPN-fed piglets than in enterally fed piglets, whereas jejunal cell proliferation and DNA mass were decreased (P < 0.05) only after 48 h of TPN. Jejunal protein synthesis was lower after 24 h of TPN, and protein mass was lower after 48 h of TPN, compared to enteral feeding. Our results show that TPN-induced mucosal villus atrophy occurs rapidly (within 24 h) and is associated with suppression of intestinal blood flow, iNOS activity, protein synthesis, and cell proliferation.