Intestinal permeability to small- and large-molecular-weight substances in the newborn rabbit.
OBJECTIVE
The authors have previously reported the occurrence of spontaneous bacterial translocation (BT) and its resolution with age in the newborn rabbit. They have also reported a close correlation between small bowel bacterial colonization (BC-SB) and BT at 1 week of age, suggesting that the presence of luminal bacteria and their production of endotoxins may increase the intestinal permeability. The aim of this study was to evaluate intestinal permeability to small and large molecules in the newborn rabbit and to correlate it with BT.


METHODS
New Zealand White rabbits (n = 96) 1, 7, 14, 21, and over 120 days (adult) of age were given either C14-labeled ethylene diamine tetraacetic acid (EDTA) (MW 290) or C14-Dextran (MW 70,000) via an orogastric tube at 1 mCi per 100 g of body weight. Five hours later, blood, urine, liver, and intestine were collected, and scintillation counting was performed after solubilization. In a separate series of rabbits (n = 136), the incidence of BT, BC-SB, and small intestinal surface area (SA) were measured.


RESULTS
Total permeability to Dextran decreased with age and was significantly reduced at 14 days of age. In contrast, total permeability to EDTA increased and was maximal in 7- to 14-day-old rabbits and began to decrease at 21 days of age. The incidence of BC-SB rapidly increased at 7 days of age and reached 100% at 14 days of age. The incidence of BT peaked at 7 days of life (30%) and then decreased with age. SA increased rapidly in the first 3 weeks and SA growth rate of 21-day-old rabbits was almost 1,400% compared with 1-day-old rabbits.


CONCLUSIONS
This study has shown an age-related reduction of intestinal permeability to large (Dextran) and small (EDTA) molecular weight particles. However, intestinal permeability to EDTA had a different pattern than Dextran, suggesting that there may be different mechanisms of intestinal permeability to different size molecules. Intestinal permeability to EDTA closely correlated with bacterial colonization and bacterial translocation, suggesting that changes in the intestinal bacterial environment may affect the intestinal permeability, possibly by activating the immune system secondary to increases in endotoxins and bacteria.
Urao
M
M
Section of Pediatric Surgery, C.S. Mott Children's Hospital and the University of Michigan Medical School, Ann Arbor 48109, USA.
Okuyama
H
H
Drongowski
R A
RA
Teitelbaum
D H
DH
Coran
A G
AG
D000818:Animals; D000831:Animals, Newborn; D018988:Bacterial Translocation / Q000187:drug effects; D002614:Chelating Agents / Q000493:pharmacokinetics*; D003911:Dextrans / Q000493:pharmacokinetics*; D004492:Edetic Acid / Q000493:pharmacokinetics*; D004755:Enterobacteriaceae / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D008970:Molecular Weight; D010539:Permeability / Q000187:drug effects; D010952:Plasma Substitutes / Q000493:pharmacokinetics*; D011817:Rabbits
D002614:Chelating Agents; D003911:Dextrans; D010952:Plasma Substitutes; D004492:Edetic Acid