Halothane의 자궁운동 억제기전에 관한 실험적 연구

Abstract

[한글]

[영문]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 investigators(Vasicka and Kretchner, 1961; Miller et al., 1966;

Munson 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 neurohumoral control(Shabanah et al., 1964a). On the other hand, some

investigators concluded that halothane has a direct stimulant action on the

adrenergic beta receptors(Klide and Aviado, 1967; Price et al., 1970) in bronchial

wall and pulmonary vessels. The present investigation was undertaken to determine

whether or not halothane depresses myometrium through the adrenergic mechanism.

Female albino rabbits, weighing approximately 2.0kg were employed. A uterine

strip, about 2.0cm in length, was carefully isolated from the non-pregnant rabbits

and suspended in a muscle chamber containing 100ml of Locke's solution, maintained

at a constant temperature of 38℃. 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**(R)

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 depressed. Further increased of the concentration of halothane

up to 3% by the Fluotec**(R) 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 tonus to the level just prior to the

addition of this anesthetic.

2. Pretreatment of the uterine strip with dichloroisoproterenol(DCI) blocked

completely the uterine inhibitory activity of isoproterenol but failed to alter the

inhibitory action of halothane. MJ-1999[dl 4-(2-isopropylamino-1-hydroxylethyl)

methanesulfonanilide HCl] or propranolol and dibenamine also produced no effects on

the uterine inhibitory action of halothane.

3. Sine the responsiveness of the uterine adrenergic receptors to catecholamines

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 contactile activity of acetylcholine but failed to alter the

inhibitory action of halothane.

5. Oxytocin and ergo alkaloid produced some effects as stimulants on the uterine

inhibitory activity of halothane but barium chloride(BaCl^^2) 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 varian hormones. It can be concluded that halothane

depress the uterine contractility by direct action on smooth muscle.