Washout rate of Tc-99m MIBI from myocardium in rats with diabetic cardiomyopathy

为了验证线粒体受损心肌中Tc-99m MIBI潴留是否减少，使用伽玛相机在固定间隔内测量阿霉素给药率的心肌MIBI吸收量，并将这些连续的心肌Tc-99m MIBI吸收量与血清肌钙蛋白T水平（代表持续心肌损伤的指标之一）和病理结果进行比较。选用10周龄Wistar-Kyoto大鼠20只作为诱发性心力衰竭模型动物和对照模型动物。10例诱发心力衰竭患者中，5例给予阿霉素2mg/kg/W皮下注射，疗程7周，其余5例给予相同剂量的阿霉素，疗程9周。将10只对照大鼠分为两组（每组5只），分别皮下注射相同剂量的生理盐水，持续7周和9周。定期测量各组大鼠血压、心率、体重。使用配备超高分辨率和针孔准直器的双头伽马相机（PRISM 2000），分别在注射3mbq MIBI后10分钟、60分钟和120分钟采集总活动和心肌活动。比较阿霉素组和对照组10分钟心肌总比和无心肌总比。Tc-99m MIBI给药120分钟后尸检，测量心脏%ID/g（注射剂量活性百分比）和血清肌钙蛋白T水平。Herman和Ferrans对阿霉素心肌病的组织学评分指数进行了估计，并根据显示细胞质空泡化和肌纤维丢失的肌细胞的数量进行了0-4级的评分。阿霉素治疗8周后血压、心率、体重与对照组比较差异有统计学意义，提示阿霉素治疗组已成功制备心力衰竭模型。阿霉素组心肌%ID/g和心脏与总比值均显著低于对照组，阿霉素组洗脱率显著高于对照组。阿霉素组和对照组2例血清肌钙蛋白均呈阳性，提示心肌组织损伤。血清肌钙蛋白T分别与10分钟、60分钟和120分钟心总比呈显著负相关。组织学评分分别与120分钟总热比和120分钟洗脱比呈正相关和负相关。线粒体Tc-99m MIBI滞留与阿霉素心肌病持续心肌损伤密切相关。此外，Tc-99m MIBI洗脱与Annexin V完成的细胞凋亡检测的相关性表明Tc-99m MIBI洗脱与线粒体功能有关。另一方面，糖尿病性心肌病大鼠给药链催产素与对照组相比，Tc-99m MIBI的心肌摄取明显减少，但差异无统计学意义，提示糖尿病性心肌病与阿霉素心衰的作用机制不同。少

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 … More 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