Surveillance of intra-abdominal pressure and intestinal barrier function in a rat model of acute necrotizing pancreatitis and its potential early therapeutic window.
OBJECTIVE
To monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.


METHODS
Sprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.


RESULTS
IAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.


CONCLUSIONS
The ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.
Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China ; Department of Gastroenterology, Guangzhou Nansha Central Hospital, Guangzhou, Guangdong Province, China.
Wei-Dong
WD
Li
Lin
L
Jia
Ya
Y
Ou
Yao-Xing
YX
Huang
Shu-Man
SM
Jiang
D006631:Amine Oxidase (Copper-Containing) / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D002756:Cholagogues and Choleretics / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D007422:Intestines; D019344:Lactic Acid / Q000097:blood; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000009:adverse effects* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D002756:Cholagogues and Choleretics; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D013656:Taurocholic Acid; D006631:Amine Oxidase (Copper-Containing); D000681:Amylases