| Project/Area Number |
09670752
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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 |
Circulatory organs internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
TANI Masato KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, DIRECTOR AND ASSISTANT PROFESSOR OF MEDICINE, 医学部, 講師 (50163613)
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| Co-Investigator(Kenkyū-buntansha) |
HOMMA Yukako KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, ASSISTANT, 医学部, 助手 (00296584)
TAKAYAMA Michiyo KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, ASSISTANT, 医学部, 助手 (60265824)
EBIHARA Yoshinori KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, ASSISTANT, 医学部, 助手 (30194020)
YAMAMURA Ken KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, ASSISTANT, 医学部, 助手 (70276260)
HASEGAWA Hiroshi KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRICS, ASSISTANT, 医学部, 助手 (00237984)
新村 健 慶應義塾大学, 医学部, 助手 (70206332)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | MYOCARDIUM / GENE TREANSFECTION / AGING / ISCHEMIC TOLERANCE / CARDIOPLEGIA / HVJ-LIPOSOME / HEAT-SHOCK PROTEIN / myocardial ischemia / heat shock protein / aging / ischemic tolerance / cold preservation / cardio plega / Casdiopelegia / Cold preservation / Caraio-plegia |
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| Research Abstract |
1. Decrease in ischemic tolerance with aging: Recovery of left ventricular function and energy metabolites, release of myocardial enzymes (CPK and LDH), and ischemia-reperfusion arrhythmias were analyzed in hearts isolated from 12, 50 or 100 week-old Fischer 344 rats. Hearts were subjected to 15 to 25 min of ischemia and 30 min of reperfusion according to the langendorff technique. Recovery of function and metabolites and release of enzymes demonstrated age-dependent decrease in ischemic tolerance. Ischemic-reperfusion arrhythmias were also more malignant in older rat hearts. Ischemic or hypoxic preconditioning performed before prolonged ischemia did not have any beneficial effects or even deteriorated myocardial damage in older hearts.
2. Gene transfection: Heat shock protein (HSP) was detected only 30% of myocytes transfected with HSP gene using HVJ-liposome+plasmid methods. This percentage was not different between 24, 48 or 72 hours after transfection. When cationic HVJ-liposome was
… More
used, efficiency was not improved remarkably. Immunocytochemical analysis with anti-HSP antibody revealed that HSP was detected with high incidence in endothelial cells, which suggested cationic HVJ-liposome might be trapped in the endothelial cells before reaching to myocytes.
3. Preservation after cold cardioplegia and iscchemia-reperfusion injury in HSP-transfected heats: Recovery of function and metabolites and release of enzymes in hearts subjected to 10 min cold cardioplegia followed by 2 hours preservation were tended to be improved when hearts of any age were transfected with HSP gene, although ischemia-reperfusion arrhythmias were not decreased by HSP transfection. On the other hand, recovery of function and metabolites, release of enzymes, and ischemia-reperfusion arrhythmias in hearts subjected to 25 min of ischemia and 30 min of reperfusion showed only insignificant improvement.
4. Simulated ischemia in isolated myocytes: In myocytes of any age that were transfected with HSP gene, increase in intracellular Ca was attenuated and recovery of cell motion was improved after 3 min of simulated ischemia (hypoxia, pH6.5, lactate 20mM, k12mM). Less
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