Mechanism of the positive staircase ; relation to the mechanism of the positive inotropic action of digitalis

一般认为洋地黄的积极内向作用的机制是通过增加细胞内钠浓度介导的。该项目的目的是确定刺激频率增加引起的发达张力的增加是否具有上述洋地黄的共同机制。收缩力研究和^<86 b> Rb摄取研究在第一年（1987年）进行，（^3H）瓦巴因结合研究在第二年（最后一年）进行。实验结果总结如下：收缩力研究：(1)刺激频率的逐步增加导致大鼠心脏左心房准备和鲤鱼心脏心室准备出现负阶梯（NS）。利亚诺定将NS转化为正阶梯（PS），然而，该药物没有改变瓦巴因的浓度依赖的正内向效应。(2)在家兔和豚鼠左心房制剂中，观察到更多心脏的PS。硝苯地平，维拉帕米或地尔硫卓将PS转化为NS。然而，这些钙拮抗剂不影响肌啡肽的浓度依赖性正性肌力作用。(3)鲤鱼心脏心室制剂具有PS，但鲤鱼心脏对strophanidin正性肌力作用的敏感性高于豚鼠左心房制剂具有PS。(4)新生大鼠和成年大鼠心室制剂分别具有PS和NS，但对小剂量瓦巴因正性肌力作用的敏感性更高。^<86>Rb摄取研究：在豚鼠心脏左心房制剂中，电刺激使^<86>Rb摄取增加。而在大鼠左心房制剂中，静息^<86 b> Rb摄取高于豚鼠心脏，刺激频率依赖性摄取低于豚鼠心脏。（^3H）瓦巴因结合研究：鲤鱼心室肌对（^3H）瓦巴因结合位点的亲和力高于豚鼠心房肌。这些结果表明，力阶梯和心肌对洋地黄正性肌力作用的敏感性之间存在明显的分离。有机钙拮抗剂或ryanoine敏感钙池可能在楼梯中起重要作用。少

It is generally accepted that the mechanism of the positive intropic effect of digitalis is mediated through an increase in intracellular Na concentrations. The objective of this project was to betermine whether an increase in developed tension caused by an increase in stimulation frequency has the common mechanism for digitalis, described above. The force of contraction stury and the ^<86>Rb uptake study were performed in the first year(1987), and the (^3H)ouabain binding study was performed in the 2nd year(final year). Experimental results were summarized as follows.1. Force of contraction study : (1) A step-wise increase in the frequency of stimulation caused a nigative staircase(NS) in left atrial preparations of the rat heart and ventricular preparations of the carp heart. Ryanodine converted the NS to a positive staircase(PS), however, this agent did not alter a concentration depenfent positive intropic effect of ouabain. (2) In left atrial preparations of rabbit and guinea pig h … More earts, the PS was observed. Nifedipine, verapamil or diltiazem converted the PS to the NS. However, these Ca antagonits did not affectthe concentration dependent positive inotropic effect of strophanthidin. (3) ventricular preparations of the carp heart has the PS. However, the sensitivity of the carp heart to the positive inotropic effect of strophanthidin was higher compared to that of the guinea pig left atrial preparations which have the PS. (4) ventricullar preparations of neonatal and abult rat hearts have the PS and NS, respectively, howrver, sensitivity to the positive inotropic effect of low dose ouabain was higher in the adult rat.2. ^<86>Rb uptake srudy : in left atrial preparations of the guinea pig heart,^<86>Rb uptake was increased by electrical stimulation. While, in left atrial preparations of the rat heart, a resting ^<86>Rb uptake was higher than in the guinea pig heart, and the stimulation frequency dependent uptake was lower.3. (^3H)ouabain binding study : affinity of the binding sites for (^3H)ouabain was higher in carp ventricular muscles compared to that of guinea pig atrial muscles. These results indicate a clear dissociation between the force staircase and the sensitivity of heart muscle to the positive inotropic effect of digitalis. Organic Ca antagonists or ryanodine-sensitive Ca pools may play an important role for the staircase. Less