Abstract
AimTo investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP).Materials and MethodsThe animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, α-tumor necrosis factor (TNF-α), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto- prostaglandin F1α were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study.ResultsPathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-α and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B2 level increased in SAP, but the ratio of thromboxane B2/6-keto- prostaglandin F1α decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05).ConclusionsThe findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.
Highlights
Despite advances in intensive care, the mortality rate of severe acute pancreatitis (SAP) still remains high, ranging from 10 up to 25% [1]
Pathologic changes noted in the pancreas in SAP significantly improved following Continuous regional arterial infusion (CRAI) with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score
The plasma thromboxane B2 level increased in SAP, but the ratio of thromboxane B2/6keto- prostaglandin F1a decreased in the treatment groups, with the combination therapy demonstrating the lowest ratio as compared to the other 3 experimental groups (P,0.05)
Summary
Despite advances in intensive care, the mortality rate of severe acute pancreatitis (SAP) still remains high, ranging from 10 up to 25% [1]. In its severe form, activation of oxygen-free radicals and microcirculatory changes, with increased endothelial barrier permeability, may result in a profound systemic inflammatory response, development of remote organ injury, potentially culminating in the multiple organ dysfunction syndrome (MODS) [2,3,4,5,6]. The inflammation and necrosis within the pancreas is a triggering factor for the development of MODS, and resolution of these local events is crucial. Somatostatin and its analogues, which have been reported to indirectly reduce MPO activity [7], release of inflammatory mediators [8], prevention of bacterial translocation [9] and ischemia-reperfusion injury [10], have been used in SAP patients [11]. The cytotoxic drug 5fluorouracil (5-Fu) has been reported to alleviate the pancreatic injury by inhibiting the inflammatory response and auto-digestion of the pancreas during the early stage of disease [12,13]
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