Experimental studies on the mechanism of the uterine inhibitory activity of halothane
[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.
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
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.
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.