Effects of Ketamine on the Isolated Uterus of Rabbits

Kim, Jong Rae

Abstract

Since McCarthy et al. (1965) demonstrated that ketamine produced a profound analgesia, preserved the protective pharyngeal reflex and elevated the arterial blood pressure in dogs, this anesthetic agent has been widely used in clinical anesthesia. However, there has still been argument about its psychotomimetic effects such as postanesthetic delirium and occasional hallucinations which appear to be commoner in adults than in children. On the other hand, imerous investigators (Chodoff and Stella, 1966; Little et al., 1971; Jawalekar et al., 1972; Galbert and Gardner, 1973; Akamatsu et al., 1974; Corssen, 1974) reported that ketamine induced contraction of the uterus and recommended this drug as a suitable obstetric anesthetic agent. The present study was undertaken to determine whether or not ketamine excites the myometrium and to elucidate the mechanism of its uterine action. Female albino non-pregnant, pregnant and postpartum rabbits weighing approximately 2.0kg were employed in this experiment. At the end of ten days following bilateral oophrectory, the non-pregnant rabbits were injected intramusculary with estrogen (2000 I.U./kg) or progesterone (5 mg/kg) daily for 4 days. An uterine strip, about 2.0 cm in length, was carefully isolated from the experimental rabbits and suspended in a muscle chamber containing 100 ml of Locke's solution, maintained at a constant temperature of 38degrees C. It was aerated with 100% oxygen bubbling through the bathing fluid by means of a sintered glass plate at the bottom of the muscle chamber. The uterine strip was attached to a Grass force displacement transducer, and the motility and tonus were recorded on a Grass model 7 polygraph. After being washed several times with fresh Locks solution, the uterine strip attained a constant motility and tonus. Ketamine then was added in concentrations ranging from 50 to 2000 r/dl to the muscle chamber. Summary 1. Ketamine produced no appreciable effect on the spontaneous motility and tonus of the uterine strip isolated from the normal non-pregnant rabbits but in a few instances it produced an increase in the amplitude and frequency of contraction. 2. Ketamine showed a tendency to increase the amplitude and frequency of contraction of the uterine strips isolated from pregnant and postpartum rabbits. 3. Uterine strips isolated from bilaterally oophorectomized rabbits showed a very weak but reguIar spontaneous contraction. Ketamine produced neither inhibitory nor stimulatory effects on these uterine strips. 4. Ketamine produced no effect on the motility and tonus of isolated uterine strips from rabbits treated with estrogen for 4 days following bilateral oophorectomy. 5. Ketamine produced, without exception, a marked stimulant action on the motility and tonus of the uterine strips isolated from rabbits treated with progesterone following bilateral oophorectomy. Pretreatment of the uterine strip from progesterone-treated rabbits with an aderenergic alpha blocking agent (dibenzyline) or adrenergic beta blocking agents (dichloroisoproterenol and propranolol) failed to alter the excitatory action of ketamine. 7. Atropine failed to alter the excitatory action of ketamine. 8. Oxytocin and ergonovine produced no effects on the excitatory aetion of ketamine on the isolated uterine strips from the progesterone-treated rabbits. From the above results it may be concluded that ketamine exerted a stimulatory action on the uterus under the influence of progesterone. This progesterone-dependent uterine stimulatory action of ketamine is not concerned with adrenergic and cholinergic mechanisms but appears to be a direct action on the uterine muscle.

Effects of Ketamine on the Isolated Uterus of Rabbits

Abstract

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