Johnson L L, Schofield L, Mastrofrancesco P, Donahay T, Farb A, Khaw B A
Department of Medicine, Rhode Island Hospital, Providence 02903, USA.
J Nucl Cardiol. 2000 Nov-Dec;7(6):590-8. doi: 10.1067/mnc.2000.108908.
Glucarate is a 6-carbon dicarboxylic acid shown to be taken up by necrotic myocytes, binding to nuclear histones in animal models of coronary occlusion, resulting in infarction. This study investigated glucarate uptake in a model of severe ischemia.
Thirty-five experiments were performed, in which a catheter-mounted stenosis (reducing lumen dimensions by 80%) was placed in the left anterior descending coronary artery (LAD) of an anesthetized, instrumented domestic swine and technetium-99m glucarate (GLU) was injected during the last minute of 5 minutes of pacing. Hemodynamic and blood flow measurements were performed at control, during pacing, and during recovery. The animals were killed; their hearts were stained with fluorescein dye and triphenyl tetrazolium chloride (TTC). Electron micography (EM; n = 6) and cell centrifugation (n = 7) were also performed. On the basis of net lactate production and severe blood flow reduction in the risk region (RR), ischemia with pacing developed in 25 animals. Fifteen of 25 animals showed tracer uptake in the RR on in vivo and ex vivo imaging (scan positive), and 10 were scan negative in the RR. Endocardial blood flow in the RR during pacing was 0.28+/-0.16 mL/g/min for scan-positive and 0.30+/-0.17 mL/g/min for scan-negative experiments (P = not significant [NS]). Transmyocardial net lactate extraction during pacing was -63%+/-44% for scan-positive and -53%+/-60% for scan-negative experiments (P = NS). Control and recovery heart rates were higher in scan-positive experiments (108+/-14 vs. 92+/-17, and 125+/-24 vs. 104+/-18, P<.02). Lactate extraction was lower during control and recovery in scan-positive animals (2+/-29 vs. 30+/-19, P = .03). Scan-positive animals had a more proximal stenosis position. Minimal necrosis was documented by means of TTC negative staining in 8 of 15 scan-positive experiments (comprising 10%+/-4.3% of RR area). EM or cell fractionation was performed in 5 of the 7 remaining scan-positive and TTC-positive hearts, and in those 5 experiments, necrosis was documented by means of EM in 2 and by means of cell fractionation in 3.
Uptake of Tc-99m glucarate was seen in the RR in a swine model of ischemia severe enough to produce myocyte injury and early cell death.
葡糖二酸是一种六碳二羧酸，在坏死的心肌细胞中可被摄取，在冠状动脉闭塞的动物模型中与核组蛋白结合，导致梗死。本研究在严重缺血模型中研究了葡糖二酸的摄取情况。
进行了35项实验，在麻醉的、已安装仪器的家猪的左前降支冠状动脉（LAD）中放置一个导管安装的狭窄装置（使管腔尺寸减少80%），并在起搏5分钟的最后一分钟注射99m锝葡糖二酸（GLU）。在对照、起搏期间和恢复期间进行血流动力学和血流量测量。处死动物；用荧光染料和氯化三苯基四氮唑（TTC）对其心脏进行染色。还进行了电子显微镜检查（EM；n = 6）和细胞离心（n = 7）。根据危险区域（RR）的净乳酸产生和严重的血流减少情况，25只动物出现了起搏诱导的缺血。25只动物中有15只在体内和体外成像时RR区域显示有示踪剂摄取（扫描阳性），10只在RR区域扫描阴性。起搏期间RR区域的心内膜血流量在扫描阳性实验中为0.28±0.16 mL/g/min，在扫描阴性实验中为0.30±0.17 mL/g/min（P = 无显著性差异[NS]）。起搏期间扫描阳性实验的跨心肌净乳酸摄取率为-63%±44%，扫描阴性实验为-53%±60%（P = NS）。扫描阳性实验中的对照和恢复心率较高（108±14对92±17，以及125±24对104±18，P<0.02）。扫描阳性动物在对照和恢复期间的乳酸摄取较低（2±29对30±19，P = 0.03）。扫描阳性动物的狭窄位置更靠近近端。在15项扫描阳性实验中的8项（占RR区域的10%±4.3%）中，通过TTC阴性染色记录到最小程度的坏死。在其余7项扫描阳性且TTC阳性的心脏中的5项中进行了EM或细胞分级分离，在这5项实验中，通过EM记录到2例坏死，通过细胞分级分离记录到3例坏死。
在严重到足以导致心肌细胞损伤和早期细胞死亡的猪缺血模型的RR区域中观察到了99m锝葡糖二酸的摄取。
