Effect of Lysine Acetylsalicylate on Biliary Lipid Secretion in Dogs

Abstract

1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.

The action of salicylates on bile flow in man.

“…This response is less than the 100% choleresis seen in the rhesus monkey (Cooper et al, 1980), and considerably less than the 600% increase in bile flow observed in the dog (Rutherford et al, 1878;Erlinger et al, 1975). No attempt was made in these studies to occlude the distal common bile duct, since it has been shown that a T-tube on dependent drainage produces complete biliary diversion (Rundle et al, 1955 Figure 1 The mean bile flow (ml kg-' 24 h-') in 15 min aliquots during the baseline period and following the administration of 1.8 g oral sodium salicylate.…”

“…Figure 2 The mean bile flow (ml kg-'24 h-')in 15 min aliquots during the baseline period and following the administration of 1.8 oral acetylsalicylate. (Erlinger et al, 1975) and rhesus monkey (Cooper et al, 1980) has shown that the increased bile flow is of canalicular origin. Bile acid secretion was unaltered in man, suggesting that as in the monkey work (Cooper et al, 1980), the salicylate choleresis depends on an increase in the bile-acid independent fraction of canalicular bile flow.…”

“…Our earlier studies (Cooper et al, 1980) in rhesus monkeys demonstrated salicylate choleresis of a lesser magnitude than that seen in dogs (Rutherford et al, 1878;Erlinger et al, 1975). The action of salicylates on bile flow in normal humans is uncertain, since previous measurements have been either indirect (Rutherford et al, 1878) or have involved patients with accidental biliary-cutaneous fistulas (Pfaff & Balch, 1897;Albu, 1900;Meiszner, 1926).…”

“…Moreover, both an increased bile flow (Rutherford et al, 1878;Pfaff & Balch, 1897;Meiszner, 1926), and a small decrease have been reported after oral ingestion of sodium salicylate (Albu, 1900). Recent work (Erlinger et al, 1975) using acetylsalicylate in the dog confirmed the presence of a powerful choleresis and noted a decrease in phospholipid and cholesterol secretion. The authors suggested that salicylate 'may be of value in the treatment of cholesterol gallstones in man'.…”

Effect of sodium acetyl salicylate on cholesterol saturation of fasting gall bladder bile, with and without chenic acid.

“…In addition, lysine acetyl salicylate has been shown in the dog to reduce the cholesterol saturation of hepatic bile by a reduction in both cholesterol and phospholipid secretion, the bile acid secretion rate remaining unchanged (Erlinger et al, 1975).…”