Effect of inositol-trisphosphate on fluid transport and protein extravasation in the obstructed small bowel.
BACKGROUND
Small-bowel obstruction is characterized by accumulation of fluid in the obstructed intestine. A pronounced inflammation in the obstructed gut wall has been shown to play an important role in the pathogenesis of the profuse fluid losses. alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent anti-inflammatory as well as antisecretory properties. The effects of alpha-Trinositol on inflammation and fluid losses in the obstructed small intestine are examined.


METHODS
A total obstruction of the proximal part of the rat jejunum was induced during 18 h by thread ligation. A small segment of the obstructed intestine, with intact vascular and nervous supply, was placed in a chamber suspended from a force displacement transducer allowing for continuous registration of net fluid transport on a Grass polygraph. Three groups were included. One group (n = 12) received low-dose alpha-Trinositol (bolus: 2 mg kg(-1); IV infusion: 10 mg kg(-1) min(-1)), a second group (n = 10) received high-dose alpha-Trinositol (bolus: 12 mg kg(-1); IV infusion: 60 mg kg(-1) min(-1)), while a control group (n = 9) received corresponding volumes of isotonic saline (bolus: 0.5 ml; IV infusions 15 microl min(-1)). Quantitative measurement of extra-vasated Evans blue albumin in the obstructed jejunum was used as a marker of inflammation.


RESULTS
High-dose alpha-Trinositol induced a significant (P < 0.001) inhibition of net fluid secretion, while low-dose alpha-Trinositol had no significant effect versus saline. In contrast, both doses of alpha-Trinositol induced significant inhibition of EB-albumin leakage (P < 0.05).


CONCLUSIONS
High-dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.
Lahti
A M
AM
Institution of Surgical Specialties, Sahlgrenska University Hospital, Göteborg, Sweden.
Cassuto
J
J
Yregård
L
L
Nellgård
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007295:Inositol Phosphates / Q000008:administration & dosage / Q000494:pharmacology*; D007415:Intestinal Obstruction / Q000503:physiopathology*; D007579:Jejunal Diseases / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; D005070:Evans Blue; C059368:atrinositol