The effect of activated protein C on experimental acute necrotizing pancreatitis.
BACKGROUND
Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30-40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis.


METHODS
Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-alpha, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured.


RESULTS
Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 +/- 0.47 versus 14.00 +/- 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor-alpha, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively).


CONCLUSIONS
APC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.
Yamanel
Levent
L
Medical Intensive Care Unit, Gülhane School of Medicine, Etlik, Ankara, Turkey. lyamanel@gata.edu.tr
Yamenel
Levent
L
Mas
Mehmet Refik
MR
Comert
Bilgin
B
Isik
Ahmet Turan
AT
Aydin
Sezai
S
Mas
Nuket
N
Deveci
Salih
S
Ozyurt
Mustafa
M
Tasci
Ilker
I
Unal
Tahir
T
D000681:Amylases / Q000097:blood; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D018988:Bacterial Translocation / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011486:Protein C / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000925:Anticoagulants; D015850:Interleukin-6; D011486:Protein C; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D000681:Amylases