1994 Fiscal Year Final Research Report Summary
The Mechanisms of Impaired Tolerance to Ischemia in Hypertrophied Heart
Project/Area Number |
05671117
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Thoracic surgery
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Research Institution | Osaka University |
Principal Investigator |
SHIMAZAKI Yasuhisa Osaka University Medical Assistant Professor, 医学部, 助教授 (60116043)
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Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Norihide Osaka University Medical Assistant, 医学部, 助手 (30263247)
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Project Period (FY) |
1993 – 1994
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Keywords | cardiac hypertrophy / intracellular calcium / intracellular sodium / intracellular pH / cardiac ischemia / myocardial protection / c-myc |
Research Abstract |
The aim of this study was to investigate the mechanism of the impaired tolerance to ischemia in hypertrophied heart and to find out how to protect hypertrophied hearts against ischemia reperfusion injury. 1)The method for the measurement of intracellular Ca, Na and pH was established in isolated rat whole heart. 2)Hypertrophied rat heart model was established by the shunting between abdominal aorta and inferior vena cave in adult male S-D rats. the weight of the hearts became two times as much as the normal hearts after 4 weeks of the shunting operation. 3)In hypertrophied rat hearts, intracellular calcium activity measured by fura-2 fluorescence was significantly increased than in normal heart after 20 minutes of normothermic ischemia. 4)Terminal cardioplegia attenuated the increased Ca fluorescence in hypertrophied hearts during reperfusion. Myocardial ATP content and the total amout of adenine nucleotide were maintained by using terminal cardioplegia both in normal and hypertrophied hearts. 5)Intracellular sodium increased after 20 minutes of ischemia and mormalized after 10 minutes of reperfusion. 6)In hypertrophied hearts, immunohistochemical examination revealed that c-myc (one of the oncogenes which regulates the hypertrophy of the myocytes) appeared 2 hours after shunting operation and showed significant hypertrophy 2 weeks after shunting operation, suggesting that the gene expression of hypertrophy occurrs just after the initiation of volume overload.
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