Continuous regional arterial infusion with fluorouracil and octreotide attenuates severe acute pancreatitis in a canine model.
OBJECTIVE
To 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).


METHODS
The 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.


RESULTS
Pathologic 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 B(2) level increased in SAP, but the ratio of thromboxane B(2)/6-keto- prostaglandin F(1α) 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).


CONCLUSIONS
The 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.
Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
Meng Tao
MT
Zhou
Bi Cheng
BC
Chen
Hong Wei
HW
Sun
Yue Peng
YP
Jin
Fa Jing
FJ
Yang
Xing
X
Zhang
Roland
R
Andersson
Qi Yu
QY
Zhang
D000681:Amylases / Q000097:blood; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004285:Dogs; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000963:Antimetabolites; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D003404:Creatinine; D000681:Amylases; D015282:Octreotide; D005472:Fluorouracil