Assessment of the total amount of CAィイD12+ィエD1 handled in the E-C coupling by analyzing postextrasystolic potentiation and OィイD22ィエD2 consumption : Systems approach

通过分析期外收缩后增强和 OD22 D2 消耗来评估 E-C 耦合中处理的 CA D12+D1 总量：系统方法

基本信息

批准号：
10558136
负责人：
SUGA Hiroyuki
金额：
$ 7.81万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We have found that postextrasystolic potentiation decays in transient alternans in the canine left ventricle (LV). We used for the curve fitting the following equation : y = a・exp[-(x-1)/κィイD2eィエD2] + b・exp[-(x-1)/κィイD2eィエD2]cos[(x-1)] +1, where x = beat number and y = normalized contractility (Emax) of the postextrasystolic beats. Internal CaィイD12+ィエD1 recirculation (RF) was obtained from τe, according to the definition : RF = exp(-1/κィイD2eィエD2). We combined RF the mechanoenergetic data and the two-fold difference of the stoichiometry between the SR CaィイD12+ィエD1 pump and the transsarcolemmal extrusion route.Using this framework, we investigated the effects of intracoronary CaィイD12+ィエD1 and epinephrine (EP) and found that CaィイD12+ィエD1 increased RF but EP did not. We obtained 40-110 micromol/kg as the total amount of CaィイD12+ィエD1 handled per beat in control and enhanced contractile state.To evaluate myocardial CaィイD12+ィエD1 handling hearts, we hypothesized that OィイD22ィエD2 wasting of Caィイ … More D12+ィエD1 handling in the E-C coupling could be reflected by a decreased RF in ryanodine-treated hearts. intracoronary ryanodine halved LV Emax without decreasing myocardial OィイD22ィエD2 consumption for the E-C coupling. We speculated this mehcanoenergetics to manifest energy wasting of CaィイD12+ィエD1 handling due to ryanodine-induced CaィイD12+ィエD1 leakage from the SR (futile cycle). Ryanorine decreased RF from 0.6 to 0.5 on average and the futile cycle was 1.4 times the effective cycle of CaィイD12+ィエD1 handled via the SR.Stunning also halved LV Emax and doubled OィイD22ィエD2 cost of Emax. We found stunning decreased RF from 0.63 to 0.43 on average and caused a considerable shift of the relation between futile cycle and CaィイD12+ィエD1 reactivity in an energy-wasteful direction. These results reasonably accounted for the doubled OィイD22ィエD2 cost of Emax in stunning. Thus, we have validated the usefulness of our integrative analysis method to evaluate myocardial CaィイD12+ィエD1 handling in beating whole hearts. (297 words) Less

我们发现犬左心室 (LV) 短暂交替时的期外收缩后增强衰减我们使用以下方程拟合曲线： y = a·exp[-(x-1)/κD2eD2] + b·exp[- (x-1)/κD2eD2]cos[(x-1)] +1，其中 x = 心跳次数，y = 归一化收缩力根据定义：RF = exp(-1/κD2eD2)，我们将 RF 与机械能数据和 2 倍差相结合，从 τe 中获得了期外收缩后搏动 (Emax)。 SR CaiD12+D1 泵与经肌膜挤出之间的化学计量使用该框架，我们研究了冠状动脉内 CaD12+D1 和肾上腺素 (EP) 的作用，发现 CaD12+D1 增加了 RF，但 EP 没有增加，作为 CaiD12+D1 处理的总量，我们得到了 40-110 微摩尔/千克。控制和增强收缩状态下的每次心跳。评估心肌 CaiD12+D1 处理心脏，我们认为，在 E-C 耦合中，OiD22D2 对 Caii D12+D1 的消耗可以通过冠脉内注射兰尼碱使 LV Emax 减半而减少，而不会减少 E-C 耦合的心肌 Oii D22 消耗。表现出能源浪费由于兰尼碱诱导的 CaiD12+D1 从 SR 泄漏（无效循环），CaiD12+D1 处理平均从 0.6 降低至 0.5，无效循环是通过 SR 处理的 Ca D12+D1 有效循环的 1.4 倍。令人惊叹的还使 LV Emax 减半，OD22D2 成本增加一倍我们发现 Emax 的击晕 RF 平均从 0.63 降低到 0.43，并导致无效循环和 CAliD12+IeD1 反应性之间的关系向能量浪费方向发生显着变化。这些结果合理地解释了 Emax 在击晕中的双倍 Oii D22D2 成本。因此，我们验证了我们的综合分析方法在评估心肌 CaD12+D1 处理方面的有效性。（297 字）少