Effects of Cisapride, Buprenorphine, and Their Combination on Gastrointestinal Transit in New Zealand White Rabbits

Fellow: Erica Feldman

Mentor: Erin Daugherity

Co-Mentor: Manuel Martin-Flores

Center for Animal Resources & Education
Sponsor: 2019 Resident Research Grants Program
Title: Effects of Cisapride, Buprenorphine, and Their Combination on Gastrointestinal Transit in New Zealand White Rabbits
Project Amount: $9,915
Project Period: June 2019 to May 2020

DESCRIPTION (provided by applicant): 

Approximately 145,000 rabbits are used annually in research, many undergoing potentially painful procedures that require analgesia. Opioids are an important analgesic to consider when performing invasive surgeries, but have been found to significantly reduce gastrointestinal (GI) motility, reduce fecal output, and delay GI transit times in rabbits. These deleterious effects can lead to GI stasis or ileus, which discourages the use of opioids in this species in both the research and clinical setting. Gastroprokinetic agents such as cisapride are effective in promoting gastric emptying in a variety of species. Cisapride has been administered anecdotally for treating GI stasis in rabbits by veterinarians, but it is not known if cisapride is efficacious in rabbits, or if it is effective at ameliorating opioid-induced GI stasis. We aim to evaluate the efficacy of cisapride on GI transit times when used as a single agent in rabbits. We will also evaluate the effects of cisapride on reducing the negative GI side effects associated with the most commonly used opioid in rabbits, buprenorphine. Using 10 healthy New Zealand White rabbits, GI transit time will be measured by administering 20 barium-filled spheres through an orogastric tube. Radiopaque barium-spheres are non-absorbable and can be detected in the feces via radiographs. Rabbits will then receive four treatments in random order: normal saline (control), buprenorphine, cisapride, and both agents combined every eight hours for two days. Feces will be monitored for the non-absorbable marker (barium-spheres) to determine GI transit times. Food and water intake, and body weight will be measured once daily for a total of five days. Each rabbit will be studied on four occasions in a crossover, randomized design, with a one week wash-out period between treatments. To our knowledge, this is the first study assessing the effect of a gastroprokinetic agent on opioid-induced ileus in rabbits. Establishing improved control over the potential GI complications of opioids with the use of cisapride will reassure clinicians that opioids can be used safely in rabbits, and will directly impact the welfare of this species in both the laboratory and clinical setting.