胆嚢内圧に及ぼすCisaprideの効果  [in Japanese] Cisapride Investigated for Effect on Intracholicystic Pressure  [in Japanese]

白色家兎のin vivoにおける胆嚢内圧変化を測定することにより,Cisaprideの胆嚢内圧に及ぼす効果について調べた。結果は,経静脈的全身投与により,投与直後には胆嚢内圧の上昇する変化と,内圧の低下する変化が,また投与20〜30分後には律動性を伴う内圧の上昇がみられた。また,Cisaprideの選択的経胆嚢動脈投与によっても胆嚢内圧の上昇が見られた。さらに,Cisaprideを胆嚢漿膜面に直接滴下投与した結果は,胆嚢内圧の上昇を認め,滴下投与量と胆嚢内圧上昇値のあいだには,ほぼ直線的なdose-responseの関係がみられた。

In the treatment of gastrointestinal disorders, Cisapride is commonly used to modify mobility in various parts of the digestive tract, from the esophagus to the colon. To investigate the efficacy of the substance as a possible therapeutic for biliary diskinesia and gallstones incurred as complications of stomach resection, we conducted experimental studies to clarify the effect of Cisapride on the gallbladder of white domestic rabbits in vivo. In canine studies, Cisapride was reported to affect the force of stretch force in Oddi's sphincter of dog, and in the human the drug is known to decrease the volume of the gallbladder, as shown by ultrasonography. In the present study the physiological effects of the drug were assessed according to three methods of administration, the ensuing intracholecystic pressure (inner gallbladder pressure), and the blood pressure. Anesthetized with Urethane (1g/kg body wt), the rabbits (adult male 3.5kg on average) were given Cisapride in one of three ways: systematic intravenous injection, injection via the cystic artery, and topical dripping directly on the surface of the gallbladder. Comparisons were made on any changes elicited in the intracholecystic pressure and in blood pressure. On intravenous administration of Cisapride (1-5mg), the following results were noted in the gallbladder: (a) an immediate and transient increase in intracholecystic pressure (in 19 of the total of 47 trials), (b) an immediate and transient decrease in intracholecystic pressure (20 out of the 47), (c) oscillation with a delayed onset of 20 to 30 minutes after dosing. In addition, the blood pressure was lowered temporally. The course of the various responses to intravenous Cisapride was recorded for 60 to 90 minutes, then we clamped the cystic duct in 3 animals in which decreased intracholecystic pressure was incurred earlier. The duct constriction effected a reversal, i. e., the intracholecystic pressure was accelerated in all three cases. This gave rise to the consideration that the immediate decrease brought on initially by Cisapride might be attributable to relaxation of the Oddi's sphincter. Therefore, in 6 animals initially showing a gallbladder response to intravenous Cisapride, we made further investigation by severing the cervical vagus nerve, In 3 cases the transient change elicited earlier was maintained and in 2 the delayed oscillation was maintained in spite of severance of the nerve. These results ruled out the possible influence of the Oddi's sphincter but left the question unanswered regarding the mechanism responsible for the drop in intracholecystic pressure. Cisapride administered via the cystic artery had no effect on the blood pressure, although the intracholecystic pressure was raised immediately. In the total of 14 topical applications, the drug consistently elevated the intracholecystic pressure but reduced the gallbladder volume.