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的系统方法来量化正常心脏中总的CaィイD12+ィエD1的处理。然而，将其直接应用于衰竭心脏是不合法的，在衰竭心脏中，无效的CaィイD12+ィエD1通过CaィイD12+ィエD1-漏水的肌浆网(SR)循环需要增加的CaィイD12+ィエD1来处理VoィイD22ィエD2。为了量化心脏衰竭时的总的CaィイD12+ィエD_1的处理，我们从早搏后增强的指数衰减部分计算了心内钙ィイD_(12+ィエ)D_1再循环分数(RF)，并将RF与减半的左心室(LV)收缩能力(E_(Max))及其O_(ィイ)D_(22)ィエ_(D2)成本相结合。在处理VoィイD22和ィエD2的情况下，冠脉内注射纳摩尔浓度的兰诺定可使Emax减半，而不显著降低CaィイD12+ィエD1。我们发现，平均而言，兰诺定显著降低了RF，从0.6降至0.5。我们还发现，无效的CaィイD12+ィエD1通过…循环此外，在兰诺定治疗后，SR从兰诺定之前的假设为零增加到&gt；1周期/搏动。我们分析了临时冠状动脉内钙ィイD12+ィエD1超负荷干预导致的轻度心力衰竭心脏准备中总钙ィイD12+ィエD1的处理情况。这一干预措施使Emax降低了40%，处理VoィイD22ィエD2的CaィイD12+ィエd1降低了30%，而不增加Emax的OィイD22ィエD2成本。我们发现，这些衰竭心脏的RF略有增加，但明显伴随着无效的CaィイD12+ィエD1周期略有增加，或CaィイD12+ィエD1的Emax反应性略有降低，或两者兼而有之。这三种可能的变化中的任何一种都可以解释Emax的OィイD22ィエD2成本不变。缺血后心肌顿抑使Emax减半，OィイD22ィエD2增加一倍。令人震惊的Rf平均从0.63降至0.43。我们发现，在顿抑心脏中，总的CaィイD12+ィエD1转运减少，无效的CaィイD12+ィエD1周期与CaィイD12+ィエD1反应的关系向能量浪费的方向发生了相当大的变化。较少

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)

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,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

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