Abstract
ObjectivesTo 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.MethodsSprague-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.ResultsIAP 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.ConclusionsThe 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.
Highlights
acute necrotizing pancreatitis (ANP) is a common acute abdominal disease, with rapid onset and progression and high mortality [1,2]
The ANP-induced changes in intra-abdominal pressure (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
It has recently been proposed that intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may have been the cause of significant morbidity and mortality during the past decade [5], and several recent studies suggest that the development of IAH/ACS in the early stages of ANP is an important contributor to severe inflammatory response and multiple organ dysfunction syndrome (MODS) [6,7]
Summary
ANP is a common acute abdominal disease, with rapid onset and progression and high mortality [1,2]. It has recently been proposed that intra-abdominal hypertension (IAH) and ACS may have been the cause of significant morbidity and mortality during the past decade [5], and several recent studies suggest that the development of IAH/ACS in the early stages of ANP is an important contributor to severe inflammatory response and MODS [6,7]. On the base of our previous experiments [8,9], we monitored IAP and other related disease indicators in a rat model of acute necrotizing pancreatitis (ANP), and aim to propose the concept of an early therapeutic window for ANP in this study
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