| Co-Investigator(Kenkyū-buntansha) |
KUMITA Sinichiro Nippon Medical School, Medicine, Associate Professor, 医学部, 助教授 (70234523)
TOBA Masahiro Nippon Medical School, Medicine, Research Associate, 医学部, 助手 (00333120)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
To validate reduced Tc-99m MIBI retention in myocardium with damaged mitochondria, myocardial MIBI uptakes of rates administrated with doxorubicin were measured in a fixed interval using gamma camera, and theses serial myocardial Tc-99m MIBI uptakes were compared with serum troponin T level as one of indicators representing ongoing myocardial damage, as well as pathological findings. Twenty Wistar-Kyoto rats of 10 weeks of age were enrolled as induced heart failure and control model animals. Five out of the ten with induced heart failure were subcutaneously administerated with 2mg/kg/W doxorubicin over 7 weeks, and the other five were administrated with the same dose of doxorubicin over 9 weeks. The ten control rats were also divided two clusters (5 each) subcutaneously administrated with the same dose of saline over 7 and 9 weeks, respectively. Blood pressure, hart rate, and body weight of each rat were measured periodically. Three minute acquisition of total and myocardial activities
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were carried out 10, 60, and 120 minutes after 3 MBq MIBI injection, using two-head gamma camera (PRISM 2000) equipped with ultra-high-resolution and pinhole collimators, respectively. Myocardial to total ratios and without ratios from 10 minutes heart to total ratio were compared between doxorubicin and control groups. Following autopsy 120 minutes after Tc-99m MIBI administration, %ID/g (percentage activity of injected dose) of heart as well as serum troponin T level were measured. Histologic scoring index by Herman and Ferrans for doxorubicin cardiomyopathy was estimated with grading on a scale of 0-4 on the basis of the number of myocytes showing cyotplasmic vacuolization and myofibrillar loss. There were significant differences of blood pressure, heart rate, and body weight after 8 weeks between doxorubicin and control groups, suggesting successful preparation for heart failure models in the former group. %ID/g of myocardium and heart to total ratios in doxorubicin group were significant lower than those in control, and washout ratios in doxorubicin group showed significantly greater values compared with those in control. All in doxorubicin group and two in control showed positive in serum troponin level, representing histologic damage of myocardium. Serum troponin T showed significant negative correlation with 10, 60, and 120 minutes heart to total ratios, respectively. Positive and negative correlation of histologic score were obtained significantly with 120 minutes heat to total ratios and 120 minutes washout ratios, respectively. Tc-99m MIBI retention in mitochondria closely related with ongoing myocardial damage in doxorubicin cardiomyopathy. Moreover, correlation of Tc-99m MIBI washout with apoptosis detection accomplished with Annexin V would indicate relationship between Tc-99m MIBI washout and mitochondrial function. On the other hand, no significant differenced were obtained between rats with diabetic cardiomyopathy administrated streptoxotocin and controls in spite of significantly decreased myocardial uptakes of Tc-99m MIBI, suggesting different mechanism between diabetic and doxorubicin heart faiuler. Less
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