General anesthesia for ureteral measurements in the rabbit

Literature search and in vitro studies on ureteral function in humans and rabbits have proven that the rabbit is a suitable animal model for the investigation of the effect of smooth muscle relaxing substances on the ureter. One of the main problems encountered was to find an appropriate anesthetic protocol for this animal model. Application of barbiturates as a monotherapy proved to be unsuitable to allow painfree preparation of the abdomen. Intravenous (iv) anesthesia consisting of ketamine-HCl/xylazine-HCl could not be considered due to interference with ureteral smooth muscle tone. Intravenous administration of ketamine-HCl induced immediate ureteral contractions with increased frequency of ureteral activity. Xylazine-hydrochloride, a mixed alpha 2-, alpha 1-adrenoceptor agonist inhibits the increase in synthesis of 3'5'-cAMP. Since the test substances used are phosphodiesterase-IV-inhibitors (rolipram and its two enantiomers), which increase 3'5'-cAMP, this type of anesthesia would interfere with the pharmacological effect to be investigated. General anesthesia using a combination of nitrous oxide (2 l/min) and oxygen (1 l/min) and a very small amount (2 mg/kg b.w.) of pentobarbital i.v. every 30 minutes, was found to be the most suitable form of anesthesia. It resulted in much more stable circulatory conditions, sufficient depth of anesthesia and the possibility to test muscle relaxing substances (PDE-IV-inhibitor) without any influence from anesthesia on their efficacy.