Pain, distress, and study endpoints are always issues of concern for an IACUC. All of these came together when the Great Eastern University IACUC reviewed a protocol from Dr. Sandy Lee that proposed to chemically induce hepatocellular carcinoma (liver cancer) in rabbits by administration of diethylnitrosamine. The protocol called for Lee to perform an open (i.e., non-laparoscopic) abdominal surgical procedure about a year after carcinoma-induction, during which a small volume of a gene construct would be injected directly into the portal vein. The intent was to gain adequate distribution of the construct through the liver so that it would localize within the previously induced carcinoma. The goal of the study was to provide a novel form of gene therapy.
Along with other required information, Lee included the following on her IACUC application relative to the induced tumor and subsequent surgery:
Animals will be anesthetized with glycopyrrolate (0.1 mg/kg, s.c.) followed by ketamine (35 mg/kg, i.m.), xylazine (5.0 mg/kg, i.m.), and acepromazine (0.75 mg/kg, i.m.). Once anesthetized, the animals will be intubated with a 5 French endotracheal tube and maintained on isoflurane anesthesia (∼1.5–2.0%) for the duration of the procedure. After the surgical procedure is completed, aspirin will be administered orally at a dosage of 100 mg/kg every 8 hours for 48 hours.
Animals will be observed at least once every hour for the first four hours following surgery, then twice a day for the next two days. They will then be observed by the research staff twice a week for the duration of the experiment. The animal care staff will observe the animals every day.
Indications that an animal requires veterinary intervention or removal from the study will include weight loss, not drinking, teeth grinding, jaundice, rapid respirations, increased heart rate, ruffled fur, and sitting in the corner of the cage and not moving.
The animals will be euthanized at three three weeks post-operative, and the livers, lungs, spleen, and several other organs will be examined histologically for primary and metastatic tumors.
Assuming drugs and dosages are appropriate, what are some questions you might ask of Lee relative to animal monitoring, pain, distress, and study endpoints if you were an IACUC member reviewing this proposal? If you believe the information provided is sufficient, explain your reasoning.
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Silverman, J. Questions for the investigator. Lab Anim 35, 15 (2006). https://doi.org/10.1038/laban1006-15a
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DOI: https://doi.org/10.1038/laban1006-15a
