Abstract
The effects of extracellular calcium concentrations and several concentration of Aconiti tuber butanol fraction, norepinephrine, ouabain on the force of isometric contraction of isolated atrial preparations obtained from rabbits were determined at $11{\sim}14$ different frequencies of contraction. Qualitatively similar results were obtained in all preparations. In most preparations, rested-state contraction was induced at the range of $120{\sim}400$ seconds stimulation interval. Over the range of intervals from 120 to 10 seconds negative inotropic effect of activation (NIEA) was predominant, so the steady-state contractile force progressively declined. At the intervals of 3 seconds, changes in the cumulated negative and positive isotropic effect of activation (PIEA) practically cancelled each other under steady-state conditions. At the interval from 3 seconds to 0.25 seconds, the additional cumulation of PIEA was greater than that of the NIEA. When the intervals between contractions were shorter than 0.25 seconds, the cumulation of the NIEA was again predominant. The positive inotropic effect of cardiac glycoside resulted at least in large part from increase in the rested-state contraction. No significant effect on the PIEA was found. The decay of the NIEA was apparently greatly accelerated in the presence of high concentration of ouabain, but this may also be a reflection of their action on the state determining the strength of the rested-state contraction. In the case of extracellular calcium concentration increment, the similar results with the ouabain treatment were obtained. Norepinephrine produced more powerful inotropic effect at shorter stimulation interval than long. The rested-state contraction and the decay of the NIEA were not significantly altered in the presence of norepinephrine, but cumulated PIEA and the amount of PIEA produced by each contraction were significantly increased. Aconiti tuber butanol fraction showed similar results with that of norepinephrine. The increment of contractile force at various contraction frequency were dose-responsive in the presence of Aconiti tuber butanol fraction. It is suggested that the positive inotropic effect of Aconiti tuber butanol fraction at various contraction frequency may be due to increase of the cumulation of PIEA and the amount of PIEA produced by each beat.
최근 강심작용 약물로 보고된 부자 부타놀 분획의 가토 심방근에서의 자극빈도에 따른 강심효과를 분석한 결과는 다음과 같다. 1) 가토 심방근의 수축력은 자극빈도에 따라 polyphasic한 수축양상을 보였으며 rested-state contraction은 $120{\sim}400sec$의 interval에서 나타났으며 이후 10sec의 간격까지는 급격한 수축력의 감소를 보이는, 축적NIEA가 PIEA의 양을 능가하는 양상을 보였으며 이 이하의 자극 빈도에서는 수축력의 증가를 보였고 대부분 0.25 sec이하의 빈도의 자극으로는 수축력의 감소를 보였다. 2) Ouabain은 저 농도에서는 interval-strength curve에 대하여 rested-state contraction의 증가와 전 자극빈도에서 비슷한 수축력의 증가를 나타내었으며, 고농도에서는 rested-state contraction의 증가와 축적 NIEA의 소멸 속도를 증가시켰으나 이는 rested-state contraction을 나타내는 시간의 단축에 따른 이차적 효과로 판정하였다. 또한 ouabain 자극빈도에 따른 강심 효과의 양상은 세포외 calcium 농도를 증가시킨 때와 유사한 양상이었다. 3) Norepinerhrine은, rested-state contraction에는 거의 영향을 주지 않았으며, 고 빈도에서 더욱 현저한 강심 작용을 나타내었고 축적 PIEA의 양의 증가와 매 beat 당 산출하는 PIEA의 양의 증가를 나타내었다. 4) 부자 부타놀 분획은 norepinephrine과 유사하고 빈도에서 수축력의 증가가 현저 하였으며, 수축력의 증가는 용량 반응 상관을 보였으며, PIEA 축적량 및 매 beat 당 산출하는 PIEA를 증가 시켰다. 따라서 고빈도에서의 강력한 수축력의 증가는 PIEA에 대한 효과에 의할 것으로 사료하였다.
(Dept. of Pharmacology, College of Medicine, Seoul National University)
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