심근 불응기에 대한 Catecholamines의 작용기전

Abstract

[한글]

[영문]

On the basis of the classification of adrenergic receptors proposed by Ahlquist (1948), the cardiac adrenergic receptor has been identified to be of beta type. This classification was originally derived from the observation regarding the relative potencies of a series of sympathomimetic amines and supported by selective inhibition of the adrenergic beta receptor by dichloroisoproterenol (Powell and Slater, 1958:Moran and Perkins,1958 : Lee and Yoo,1964) and pronethalol (B1ack and Stephenson,1962). On the other hand, Cotten and Walton (1951), measuring change in ventricular contractile force with strain gauge arches in open-chest dogs, observed diminished responses to epinephrine following administration of Dibenamine, a known alpha adrenergic blocking agent, and suggested the presence of alpha adrenergic receptor in the heart. Further evidence supporting this view is Presented by Govier et at. (1966) who investigated the response of the atrial functional refractory period to catecholamines by using phenoxyben-zamine and pronethalol and concluded that both alpha and beta adrenergic receptors were present in the myocardium.

Thus the question whether the cardiac adrenergic receptor is a beta type, alpha type or both may be considered unestablished, and further studies are indicated. In this study an attempt was made, employing various adrenergic blocking agents, to determine which type the receptors involving the atrial functional refractory period belong to.

Hea1thy albino rabbits weighing approximately 2.0 kg of body weight were employed in this experiment The functional refractory periods of isolated rabbit atria were determined by the paired stimulus technique as described by Govier et at. (1966).

Results

1. The mean threshold intensity and refractory period for normal rabbits were 9.8±1.52 volts and199±4.9 msec. respectively. There was no significant correlation between talc changes of refractory period and heart rate.

2. Norepinephrine, epinephrine and isoprterenol did not increase the refractory period but markedly decreased it The order of potency of the three amines in producing talc decrease was isoproterenol> norepinephrine ≥ epinephrine.

3. Pronethalol, which is a blocking agent of adrenergic beta-receptors, inhibited completely the decrease in refractory period induced by norepinephrine.

4. Propranolol, a potent adrenergic beta-receptor blocking agent, also completely inhibited the decrease in refractory period by norepinephrine.

5. MJ-1999, less potent adrenergic beta-receptor blocking agent, blocked markedly but not completely the decrease of refractory period by norepinephrine.

6. Pretreatment with either phenoxybenzamine or phentolamine, an adrenergic alpha-receptor blocking agent, did not modify the decrease in refractory period induced by norepinephrine.

From the above results, it is concluded that norepinephrine. epinephrine and isoproterenol decrease the atrial functional refractory period and this decrease is considered to be a function of beta-adrenergic receptors in the heart.