Experimental Studies on the Mechanism of the Uterine Inhibitory Aetivity of Halothane

Kim, Sung Yell

Abstract

Halothane has become very popular in recent years and is an excellent agent in obstetric anesthesia (Bosomworth, 1962; Stoelting, 1964; Wilson and Vandewater, 1965) but the uterine depressant effect of halothane has been established from reports of numerous inveatigators(Vasicka and Kretchner, 1961; Miller et al., 1966; Munsoa et aL, 1969). Ahlquist (1966) reviewed the hypothesis which he introduced to explain the differing effects of adrenergic drugs in different body sites. He defined the adrenergic receptor as an entity in or on effector cells which interacts with adrenergic agonists to elicit the response characteristic of the cell. The alpha receptor is concerned with uterine contraction, and the beta receptor mediates inhibition of the uterine musculature. It was concluded that the myometrium in both the intact and isolated uterus is fully under neuro-humoral control(Shabanah et al., 1964a). On the other hand, some investigators concluded that halothane has a direct stimulant action on the adrenergic beta receptors in bronchial wall and pulmonary vessels. (Klide and Aviado, 1967; Price et al., 1970). The present investigation was undertaken to determine whether or not halothane depresses myometrium through the adrenergic mechanism. Female albino rabbits, weighing approximately 2.0 kg were employed. A uterine strip, about 2.0 cm in length, was carefully isolated from the non-pregnant rabbits and suspended in a muscle chamber containing 100 ml of Locke's aolution, maintained at a constant temperature of 38 â„ƒ. A mixture of 95% oxygen and 5% carbon dioxide was bubbled through the bathing fluid by means of a sintered glass plate at the bottom of the muscle chamber. The uterine segment 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 Locke's solution for a period of 30 minutes, the uterine segment attained a constant motility and tonus. Halothane then was added by diverting the mixed gas stream through a Fluotec® Mark II Vaporizer.
RESULTS
1. When the vaporizer was set at a concentration of 2% or less, halothane produced no appreciable effects on the spontaneous motility and tonus of the normal non-pregnant uterine segment. However, at a concentration of 2.5%, the motility and tonus were markedly depreased. Further increase of the concentration of halothane up to 3% by the Fluotec® Mark II vaporizer, depressed almost completely the motility of the uterine segment. After cessation of the perfusion of halothane, the uterine segment resumed its motility and tonua to the level just prior to the addition of this anesthetic. 2. Pretreatment of the uterine strip with dichloroisoproterenol(DCT) blocked completely the uterine inhihitory activity of isoproterenol but failed to alter the inhibitory action of halothane. MJ-1999[dl 4-(2-isopropylamino-I-hydroxylethyl) methanesulfonanilide HC1] or propranolol and dibenamine also produced no effects on the uterine inhibitory action of halothane. 3. Since the responsiveness of the uterine adrenergic receptors to cateeholamines is greatly influenced by ovarian hormones, effects of halothane on adrenergic receptors were examined on uterine strips isolated from oophorectomized, estrogen-treated and progesterone-treated rabbits. Halothane produced similar inhibitory effect, quantitatively as well as qualitatively, on these uterine strips to that on the non-pregnant uterus and the effect was found to be unrelated to adrenergic receptors. 4. Acetylcholine produced an appreciable stimulating effect on the spontaneous motility and tonus of the normal non-pregnant uterine segment, and atropine blocked completely the uterine contractile activity of acetylcholine but failed to alter the inhibitory action of halothane. 5. Oxytocin and ergot alkaloid produced some effects as stimulants on the uterine inhibitory activity of halothane but barium chloride (BaCl2) was found significantly to antagonize it. SUMMARY: A high concentration of halothane (above 2.5%) produced uterine inhibitory activity in vitro and these mechanisms were not concerned with adrenergic and cholinergic receptors, or ovarian hormones. It can be concluded that halothane depress the uterine contractility by direct action on smooth muscle.

Experimental Studies on the Mechanism of the Uterine Inhibitory Aetivity of Halothane

Abstract

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