| Project/Area Number |
16591404
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Nara Medical University |
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Principal Investigator |
YOSHIKAWA Yoshiro Nara medical university, School of medicine, assistant professor, 医学部, 講師 (40343420)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJI Tsuyoshi Nara medical university, School of medicine, assistant professor, 医学部, 講師 (50295804)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | mechanoenergetics / failing heart / calpain inhibitor / cross-circulation method / gene transfer / NCX inhibitor / 心力学的・エネルギー学的評価 / コンダクタンスカテーテル |
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| Research Abstract |
We tried to measure mouse left ventricular pressure, volume, and oxygen consumption ( = arteriovenous oxygen content differencexcoronary flow) to establish a new evaluation of its mechanoenergetics in the whole heart preparation by using the cross-circulation method. We obtained a curved end-systolic pressure-volume relation as rats, in contrast to a linear end-systolic pressure-volume relation in dogs, rabbits, and humans. However, we suspected to obtain a linear oxygen consumption per beat (VO_2)-systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy per beat) relation as in other species. Thus PVA can be a good index for assessing rat left ventricular mechanoenergetics. The VO_2 intercept and slope of the linear VO_2-PVA relation correspond to those in other species. It is hardly to establish the cross-circulation method in mouse, because of difficulty of preparation of the isolated mouse heart and the accuracy of measurement apparatus. We want to
… More
expect the future development.
In the other hand we hypothesized that LV contractile failure similar to that after high Ca^<2+> infusion occurs after ischemic-reperfusion. To test this hypothesis, we investigated LV mechanical work and energetics in the cross-circulated rat hearts that underwent global ischemia and reperfusion (I/R). Mean systolic PVA at midrange LV volume (PVA_<mLVV>) was significantly decreased. Mean VO_2 intercept (mainly VO_2 for the total Ca^<2+> handling in E-C coupling) of VO_2-PVA linear relation was significantly decreased without change in its slope. After reperfusion with NCX inhibitor, or calpain inhibitor-1, each decrease in mean PVA_<mLVV> and VO_2 intercept was reduced. These results suggested that calpain inhibitor protected the heart against I/R injury associated with blockade of the proteolysis. NCX inhibitor also protected the heart against I/R injury but its protection was associated with reduction of initial intracellular Ca^<2+> overload resulting in energy waste. Less
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