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

正楼梯机构；

• 批准号: 62560300
• 负责人: TEMMA Kyosuke
• 金额: $ 1.09万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62560300/
• 关键词: Staircase Phenomenon; Digitalis; 収縮力増大作用; ^<86>Rb取り込み; (^3H)ウワバイン結合; 心臓; (^3H)ウワバイン; scatchardプロット; ウサギ; モルモット; コイ; staircase; ウワバイン

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

一般认为洋地黄的正性内向效应的机制是通过增加细胞内Na浓度来介导的。本项目的目的是确定刺激频率增加引起的发达张力增加是否具有上述洋地黄的共同机制。第<86>一年（1987年）进行了收缩力和^ Rb摄取研究，第二年（最后一年）进行了（^3 H）哇巴因结合研究。实验结果如下：1.收缩力研究：（1）逐步增加刺激频率，在大鼠心脏左心房准备和鲤鱼心脏心室准备中引起负阶梯（NS）。Ryanodine使NS变为正阶梯（PS），但不改变哇巴因浓度依赖性的正内向效应。(2)在家兔和豚鼠的左心房标本中， ...更多信息 观察PS。硝苯地平、维拉帕米或地尔硫卓可使PS转为NS。但这些钙拮抗剂不影响毒毛旋花子苷的浓度依赖性正性肌力作用。(3)鲤鱼心室标本具有PS。然而，鲤鱼心脏对毒毛旋花子苷正性肌力作用的敏感性高于具有PS的豚鼠左心房制剂。(4)新生和成年大鼠心室标本分别具有PS和NS，但成年大鼠对小剂量哇巴因的正性肌力作用敏感性较高. Rb<86>摄取研究：在豚鼠左心房制备物中，<86>电刺激可增加Rb摄取。而大鼠左心房<86>的静息摄取率高于豚鼠，刺激频率依赖性摄取率低于豚鼠.（^3H）哇巴因结合研究：鲤鱼心室肌中（^3H）哇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ryanodine敏感的钙池可能发挥重要作用的楼梯。少

项目成果

Kyosuke Temma: "Carp(Cyprinus carpio) heart has a high sensitivity to the positive inotropic effect of strophanthidin despite negative force-frguency relationships." General Pharmacology. 18. 617-622 (1987)

Kyosuke Temma：“尽管力-频率关系呈负向，但鲤鱼心脏对旋花树素的正性肌力作用具有高度敏感性。”

Kyosuke Temma: "Ca entry blockers, force staircase and the onset of the positive inotropic action of cardiotonic steroids in isolated cardiac muscle."

Kyosuke Temma：“Ca 进入阻滞剂、力量阶梯以及强心类固醇在离体心肌中的正性肌力作用的开始。”

Kyosuke Temma.: General Pharmacology. 18. 617-622 (1987)

Kyosuke Temma.：普通药理学。