Macro-micro correspondence in mechanoenagetics of failing hearts

衰竭心脏机械动力学中的宏观与微观对应

• 批准号: 09470009
• 负责人: SUGA Hiroyuki
• 金额: $ 3.78万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470009/
• 关键词: heart failure; ryanodine; stunning; calcium paradox; Emax; postextrasystolic potentiation; sarcoplasmic reticulum; excitation-contraction coupling; 不全心; 収縮期末圧容積関係; 収縮期末圧容積面積; 酸素消費量; エネルギー変換効率; 生体位心; 心機能の評価; メカノエナジェティクス; カルシウム動態; 統合生理学

We have developed an organ-level systems approach to quantify total CaィイD12+ィエD1 handling in normal hearts. However, its direct application to failing hearts, where futile CaィイD12+ィエD1 cycling via the CaィイD12+ィエD1-leaky sarcoplasmic reticulum (SR) required an increased CaィイD12+ィエD1 handling VoィイD22ィエD2, was not legitimate. To quantify total CaィイD12+ィエD1 handling even in such failing hearts, we calculated internal CaィイD12+ィエD1 recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation (PESP) and combined the RF with the halved left ventricular (LV) contractility (Emax) and its OィイD22ィエD2 cost.We applied this new integrative method to three kinds of failing hearts.1. Failing hearts after intracoronary ryanodine at nanomolar concentrations halved Emax without significantly decreasing CaィイD12+ィエD1 handling VoィイD22ィエD2. We found that ryanodine significantly decreased RF from 0.6 to 0.5 on the average. We also found that futile CaィイD12+ィエD1 cycling via … More the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine.2. We analyzed total CaィイD12+ィエD1 handling of the LV in the mildly failing heart preparation induced by a temporary intracoronary CaィイD12+ィエD1 overloading intervention. This intervention decreased Emax by 40% and CaィイD12+ィエD1 handling VoィイD22ィエD2 by 30% without increasing the OィイD22ィエD2 cost of Emax. We found that these failing hearts had a slightly but significantly increased RF accompanied by either a slightly increased futile CaィイD12+ィエD1 cycling or a slightly decreased CaィイD12+ィエD1 reactivity of Emax, or both. Any of these three possible changes can account for the unchanged OィイD22ィエD2 cost of Emax.3. Postischemic myocardial stunning halved Emax and doubled OィイD22ィエD2 cost of Emax. Stunning decreased RF from 0.63 to 0.43 on the average. We found a decreased total CaィイD12+ィエD1 transport and a considerable shift of the relation between futile CaィイD12+ィエD1 cycling and CaィイD12+ィエD1 reactivity in an energy-wasteful direction in the stunned heart. Less

我们开发了一种器官水平系统方法来量化正常心脏中总的 CaiD12+D1 处理，但是，其直接应用于衰竭心脏，其中通过 CaiD12+D1 D1 渗漏肌浆网 (SR) 进行徒劳的 CaiD12+D1 循环需要一个。增加了CaiD12+D1处理VoiD22D2，不合法地量化总数。即使在这种衰竭的心脏中，CaiD12+D1 也能处理，我们根据期外收缩后增强 (PESP) 的指数衰减分量计算了内部 CaiD12+D1 再循环分数 (RF)，并将 RF 与减半的左心室 (LV) 收缩力 (Emax) 及其我们将这种新的积分方法应用于三种失败的心脏。 1．纳摩尔浓度的冠脉内兰尼碱使 Emax 减半，但没有显着降低 CaiD12+D1 处理 VoiD22D2 我们发现，兰尼碱将 RF 平均从 0.6 显着降低至 0.5 我们还发现无效的 CaD12+ D1 循环通过…更多 SR 增加至 >1 个循环/。在ryanodine之后从ryanodine之前的大概零击败。2。分析了临时冠状动脉内 CaiD12+D1 超负荷干预引起的轻度衰竭心脏准备中 LV 的总 CaiD12+D1 处理。这种干预使 Emax 降低 40%，CaiD12+D1 处理 VoiD22D2 降低 30%，而不会增加 Emax 的 OiD22D2 成本。我们发现这些衰竭的心脏有轻微但显着的增加RF 伴随着 Emax 的无效 CaiD12+D1 循环略微增加或 CaiD12+D1 反应性略微降低，或者这三种可能的变化中的任何一个都可以解释 Emax.3 的 OiD22 ED2 成本不变。 Emax 的 OD22 成本从 0.63 降低了一倍。我们发现，在昏迷的心脏中，CaiD12+D1 的总转运量减少了，并且无效的 CaiD12+D1 循环与 CaiD12+D1 反应性之间的关系发生了相当大的转变。

项目成果

Syuu Y,Araki J,Lee S,Suzuki S,Mizuno J,Mohri S,Mikane T,Shimizu J,Takaki M,Suga H: "Effects of Ca^<2+> and epinephrine on Ca^<2+> recirculation fraction and total Ca^<2+> handling in canine left ventricles."Jpn J Physiol. 48・2. 123-132 (1998)

Syuu Y、Araki J、Lee S、Suzuki S、Mizuno J、Mohri S、Mikane T、Shimizu J、Takaki M、Suga H：“Ca^<2+> 和肾上腺素对 Ca^<2+> 再循环分数的影响犬左心室中的总Ca^<2+>处理。”Jpn J Physiol.48・2.123-132(1998)

Shimizu J,Araki J,Mizuno J,Lee S,Syuu Y,Hosogi S,Mohri S,Mikane T,Takaki M,Taylor TW,Suga H: "A new integrative method to quantify total Ca^<2+> handling and futile Ca^<2+> cycling in failing hearts."Am J Physiol. 275. H2325-H2333 (1998)

Shimizu J,Araki J,Mizuno J,Lee S,Syuu Y,Hosogi S,Mohri S,Mikane T,Takaki M,Taylor TW,Suga H：“一种量化总 Ca^<2> 处理和无用 Ca 的新综合方法

Araki, J., Matsubara, H., Shimizu, J., Mikane, T., Mohri, S., Mizuno, J., Takaki, M., Ohe, T., Hirakawa, M., Suga, H.: "Weibull distribution function for cardiac contraction : Integrative analysis"Am. J. Physiol.. 277. H1940-H1945 (1999)

Araki, J.、Matsubara, H.、Shimizu, J.、Mikane, T.、Mohri, S.、Mizuno, J.、Takaki, M.、Ohe, T.、Hirakawa, M.、Suga, H.：

Shimizu J: "A new integrative method to quantify total CaィイD12+ィエD1 handling and futile CaィイD12+ィエD1 cycling in failing hearts"Am J Physiol. 275. H2325-2333 (1998)

Shimizu J：“一种量化衰竭心脏中总 CaD12+D1 处理和无效 CaD12+D1 循环的新综合方法”Am J Physiol 275. H2325-2333 (1998)

Lee S,Araki J,Imaoka T,Maesako M,Iribe G,Miyaji K,Mohri S,Shimizu J,Harada M,Ohe T,Hirakawa M,Suga H: "Energy-wasteful total calcium handling underlies increased O_2 cost of contractility in canine stunned heart."Am J Physiol. (In press).

Lee S,Araki J,Imaoka T,Maesako M,Iribe G,Miyaji K,Mohri S,Shimizu J,Harada M,Ohe T,Hirakawa M,Suga H：“能量浪费的总钙处理是 O_2 收缩成本增加的基础