Effect of hyperbaric oxygen and ulinastatin on plasma endotoxin, soluble CD14, endotoxin-neutralizing capacity and cytokines in acute necrotizing pancreatitis.
BACKGROUND
We sought to study the effect of a combination therapy comprised of hyperbaric oxygen (HBO) and ulinastatin on the plasma levels of endotoxin, soluble CD14 (sCD14), endotoxin neutralizing capacity (ENC) and cytokines in acute necrotizing pancreatitis (ANP) in rats.


METHODS
We randomly allocated 90 Sprague-Dawley rats into 6 groups: group 1 (ordinary control), group 2 (sham operation), group 3 (ANP), group 4 (ANP with HBO), group 5 (ANP with ulinastatin) and group 6 (ANP with HBO and ulinastatin). We induced ANP by retrograde injection of 3.5% sodium taurocholate (2.5 mL/kg) via the pancreatic duct. Five minutes after induction, animals in groups 5 and 6 were infused with ulinastatin (20 000 U/kg) via the portal vein. Thirty minutes after induction, animals in groups 4 and 6 received HBO therapy. We collected samples 3, 6 and 10 hours after induction of ANP.


RESULTS
We found that the plasma level of endotoxin in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3 h, p < 0.001; 6 h, p = 0.014) and group 6 (both p < 0.001). The level of plasma sCD14 in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3, 6 h, both p = 0.001) and group 6 (3 h, p < 0.001; 6 h, p = 0.001). The plasma endotoxin and sCD14 levels in group 6 were significantly lower than in groups 4 and 5. The plasma ENC level in group 6 was significantly higher than in groups 3, 4 and 5 (p < 0.001). The ENC level in groups 4 and 5 were higher than in group 3, but there was no significant difference. The plasma level of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in group 6 were significantly lower than in groups 3, 4 and 5 (p < 0.001). The TNF-alpha and IL-6 levels in groups 4 and 5 were lower than in group 3, but there was no significant difference.


CONCLUSIONS
The use of an early combination therapy of HBO and ulinastatin was more effective than either therapy alone in the treatment of ANP.
Hou
Jing
J
Beijing Tongren Hospital, Capital Medical University, China.
Zhu
Ming-Wei
MW
He
Xiu-Wen
XW
Wei
Jun-Ming
JM
Li
Yong-Guo
YG
Tang
Da-nian
DN
D000818:Animals; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D006931:Hyperbaric Oxygenation / Q000379:methods*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000187:drug effects; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects
D016207:Cytokines; D004731:Endotoxins; D006023:Glycoproteins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; C028665:urinastatin