Does intestinal permeability lead to organ failure in experimental necrotizing enterocolitis?
OBJECTIVE
The rat gavage model is used to explore the pathogenesis and treatment of necrotizing enterocolitis (NEC). Although intestinal histological damage is seen in this model, intestinal perforation is rarely observed. Whether organ failure occurs in this model is largely unknown. We hypothesised that increased intestinal permeability leads to organ failure in experimental NEC.


METHODS
NEC was induced in neonatal rats by gavage feeding of hypertonic formula plus exposure to hypoxia plus oral lipopolysaccharide (4 mg/kg per day daily). Breast-fed rats were used for comparison. At 92 h, lactulose (3 mg) and mannitol (2 mg) were administered orally in 0.1 ml water. Four hours later, rats were killed and blood samples collected. Lactulose and mannitol were measured by gas chromatography-mass spectrometry and lactulose/mannitol ratio calculated as index of intestinal permeability. Plasma cardiac troponin-I was measured by ELISA as a marker of cardiac damage and plasma creatinine measured spectrophotometrically as a marker of renal failure.


RESULTS
Experimental NEC induced an increase in intestinal permeability (P = 0.0002). This was associated with cardiac damage (P < 0.0001), and renal failure (P = 0.004).


CONCLUSIONS
Intestinal permeability is increased in experimental NEC in association with increased cardiac damage. Rat mortality may be due to cardiac failure secondary to an inflammatory response caused by increased intestinal permeability.
Surgery Unit, Department of Surgery, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
Augusto
A
Zani
Marco
M
Ghionzoli
Giuseppe
G
Lauriti
Mara
M
Cananzi
Virpi V
VV
Smith
Agostino
A
Pierro
Paolo
P
De Coppi
Simon
S
Eaton
D000818:Animals; D000831:Animals, Newborn; D002463:Cell Membrane Permeability / Q000502:physiology*; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007792:Lactulose / Q000493:pharmacokinetics; D008353:Mannitol / Q000493:pharmacokinetics; D009102:Multiple Organ Failure / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D008353:Mannitol; D007792:Lactulose