The development of evaluating method for oxygen wasting effects by cardiotonic agents

强心剂耗氧效应评价方法的建立

• 批准号: 04557041
• 负责人: SUGA Hiroyuki
• 金额: $ 5.5万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557041/
• 关键词: Emax; PVA; left vantricle; oxygen consumption; cardiotonic agent; pimobendan; pentobarbital

This head investigator proposed and established Emax (maximal elastance) as a index of cardiac contractility and PVA as a total mechanical energy derived from cardiac contraction in fundamental physiological studies. Furthermore, VO_2, which is a product of arteriovenous oxygen content difference per beat and coronary flow has been presented to be linearly correlated with PVA.In the first year of this project, by using this Emax-PVA-VO_2 framework, we examind the effects of a cardiotonic agent, pimobendan which has a calcium sensitizing effect, on cardiac mechanoenergetics in normral hearts. In the second year of this project we tried to make acute failing heart model to examine the effects of cardiotonic agents. For experiments, we prepared a cross-circulated blood perfused excised heart from a pair of dogs. At first we obtained control Emax, PVA and VO_2 at different end-diastole volume by measuring pressure and volume. VO_2-PVA relation was linear. The reciprocal of the slope of this relation is contractile efficiency converting PVA-dependent VO_2 into total mechanical energy. PVA-independent VO_2 at PVA=0 demonstrates calcium handling energy in excitation-contraction coupling. We obtanined reasonable values in all of those parameters. Pimobendan or pentobarbital dose-dependently increased or decreased Emax, PVA and VO_2 and shifted VO_2-PVA relation upwards or downwords. Neither pimobendan nor pentobarbital changed contractile efficiency, but increased or decreased PVA-independent VO_2. The relation of PVA-independent VO_2 and Emax was linear and its slope demonstrates oxygen cost of contractility ; this cost was similar to calcium. Therefore, pimobendan and pentobarbital increased or decreased Emax without changing oxygen costs of PVA and contractily. Further studies will be done by using failing hearts model to compare with nomal hearts.

该首席研究员在基础生理学研究中提出并建立了Emax（最大弹性）作为心脏收缩力的指标，PVA作为心脏收缩产生的总机械能。此外，VO_2（每次心跳动静脉氧含量差和冠状动脉流量的乘积）已被证明与 PVA 呈线性相关。在该项目的第一年，通过使用此 Emax-PVA-VO_2 框架，我们检查了效果强心剂匹莫苯对正常心脏的心脏机械能有钙敏化作用。在这个项目的第二年，我们尝试制作急性衰竭心脏模型来检查强心剂的效果。为了进行实验，我们准备了一对狗的交叉循环血液灌注离体心脏。首先通过测量压力和容量获得不同舒张末期容量下的对照Emax、PVA和VO_2。 VO_2-PVA呈线性关系。该关系的斜率的倒数是将依赖于 PVA 的 VO_2 转换为总机械能的收缩效率。 PVA=0 时与 PVA 无关的 VO_2 表现出兴奋-收缩耦合中的钙处理能量。我们获得了所有这些参数的合理值。匹莫苯丹或戊巴比妥剂量依赖性地增加或减少Emax、PVA和VO_2，并使VO_2-PVA关系向上或向下移动。匹莫苯丹和戊巴比妥均不会改变收缩效率，但会增加或减少不依赖于 PVA 的 VO_2。与PVA无关的VO_2和Emax呈线性关系，其斜率表明收缩性的耗氧量；这个成本与钙相似。因此，匹莫苯丹和戊巴比妥增加或减少Emax而不改变PVA和收缩的氧消耗。进一步的研究将通过使用衰竭心脏模型与正常心脏进行比较来进行。

项目成果

M Takaki,T Namba,J Araki,K Ishioka,H Ito,T Akashi,LY Zhao,DD Zhao,M Liu,W Fujii,H Suga: "(How to measure cardiac energy expenditure)In Ischemia-reperfusion in cardiac surgery" Kluwer Academic Publishers, 448 (1993)

M Takaki,T Namba,J Araki,K Ishioka,H Ito,T Akashi,LY Zhu,DD Zhao,M Liu,W Fujii,H Suga：“（如何测量心脏能量消耗）心脏手术中的缺血再灌注”

T Namba,M Takaki,J Araki,K Ishioka,H Suga: "Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle" Cardiovascular Research. 28. 557-565 (1994)

T Namba、M Takaki、J Araki、K Ishioka、H Suga：“犬左心室戊巴比妥钠负性和正性肌力作用的能量学”心血管研究。

T.Namba,M.Takaki,J.Araki,K.Ishioka,H.Suga: "Energetics of the negative and positive inotropism on pentobarbitone sodium in the canine left ventricle" Cardiovascular Research. 28 (印刷中). (1994)

T.Namba、M.Takaki、J.Araki、K.Ishioka、H.Suga：“犬左心室戊巴比妥钠负性和正性肌力作用的能量学”28（出版中）。

Taketoshi Namba, Miyako Takaki, Junichi Araki, Kazunari Ishioka, Hiroyuki Suga: "Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left vantricle" Cardiovascular Research. 28. 557-565 (1994)

Taketoshi Namba、Miyako Takaki、Junichi Araki、Kazunari Ishioka、Hiroyuki Suga：“犬左心室戊巴比妥钠负性和正性肌力作用的能量”心血管研究。

Miyako Takaki, Taketoshi Namba, Junichi Araki, Kazunori Ishioka, Haruo Ito, Takuji Akashi, Ling Yun Zhao, Dan Dan Zhao, Miao Liu, Wakako Fujii, Hiroyuki Suga: "How to measure cardiac energy expenditure" Ischemia-reperfusion in cardiac surgery. 403-419 (19

Miyako Takaki、Taketoshi Namba、Junichi Araki、Kazunori Ishioka、Haruo Ito、Takuji Akashi、Ling Yun Zhao、Dan Dan Zhu、Miao Liu、Wakako Fujii、Hiroyuki Suga：“如何测量心脏能量消耗”心脏手术中的缺血再灌注。