A METHOD TO QUANTITATIVELY COMPARE IN-VIVO THE EFFECTS OF GALLSTONE SOLVENTS ON INTESTINAL MUCOSAL FUNCTION - A CONTROLLED-STUDY COMPARING MONO-OCTANOIN WITH METHYL TERT-BUTYL ETHER IN THE RAT

During contact dissolution of gallstones, solvents may escape from the gallbladder and damage the intestinal mucosa, In order to compare the extent of this potential injury, we developed a method to objectively quantify the effects of two commonly used cholesterol solvents, methy l tert-butyl ether and mono-octanoin, on mucosal transport function in the rat intestine. Two intestinal segments in each of 184 anesthetize d rats were cannulated. Three milliliters of either solvent were insti lled in one segment and left for varying periods of time, while saline was instilled in the other as control, The segments were then washed and perfused for 45 min with an isotonic solution containing [H-3]poly ethylene glycol 4000 (a nonabsorbable reference marker) and either [C- 14]alpha-aminoisobutyric acid (a marker for active absorption) or [C-1 4]mannitol (a marker for passive permeability). Methyl tert-butyl ethe r caused more inhibition of alpha-aminoisobutyric acid absorption (64% ) than mono-octanoin (48%) and a greater reduction of dry weight per c entimeter of the perfused segment (22%) compared with mono-octanoin (1 0%). Such effects appeared after only 1 min of solvent exposure end di d not appreciably increase with longer exposures. Permeation of mannit ol increased by 26% after 1 min of exposure to mono-octanoin and by 54 % after a similar period of exposure to methyl tert-butyl ether, Longe r exposures to both solvents did not seem to cause progressive increas es in mannitol permeation. The results indicate that brief exposure of the rat jejunum to either of the two solvents causes a reduction in a ctive transport ([C-14]alpha-aminoisobutyric acid absorption), an incr ease in passive permeability (mannitol permeation), and a loss of muco sal constituents, We conclude that the intestinal mucosa is susceptibl e to solvent damage and may be used as a selectively sensitive model t hat can characterize the biological injury of gellstone solvents, The study also suggests that escape of the currently available solvents in to the small intestine in patients undergoing contact dissolution of g allbladder stones may cause injury to the small intestine.