Okada David R, Johnson Gerald, Okada Robert D
Brigham and Women's Hospital, Harvard Medical School, Boston 02446, MA, USA.
University of Tulsa, Tulsa 74104, OK, USA ; University of Oklahoma Health Sciences Center, 6208 S. Oswego Ave, Tulsa 74136, OK, USA.
EJNMMI Res. 2014 Aug 1;4:42. doi: 10.1186/s13550-014-0042-6. eCollection 2014.
Recent technical developments using solid-state technology have enabled rapid image acquisition with single photon emission computed tomography (SPECT) and have led to a renewed interest in technetium-99m-teboroxime (Tc-99m-teboroxime) as a myocardial imaging agent. Tc-99m-teboroxime has demonstrated high myocardial extraction, linear myocardial uptake relative to flow even at high flow rates, rapid uptake and clearance kinetics, and differential clearance in the setting of ischemia. However, the myocardial clearance kinetics of Tc-99m-teboroxime in a model of myocardial injury has not been previously reported. Thus, the purposes of this study were to use a canine model of ischemia-reperfusion to (1) compare Tc-99m-teboroxime clearance kinetics in normal and ischemic-reperfused myocardium and (2) assess the utility of Tc-99m-teboroxime clearance kinetics in determining the severity of injury following ischemia-reperfusion.
Thirteen dogs underwent left circumflex coronary artery (LCx) occlusion for either 30 min (IR30, n = 6) or 120 min (IR120, n = 7), followed by reperfusion, and finally Tc-99m-teboroxime administration 120 min after reperfusion. Microsphere blood flows were determined at baseline, during occlusion, after reperfusion, and before euthanasia. Post-mortem, area at risk was determined using Evans blue dye, and viability was determined using triphenytetrazolium chloride (TTC) staining. The hearts were then subdivided into 24 pieces and Tc-99m activity was measured in a well counter.
TTC-determined infarct area as a percentage of total left ventricular myocardium was 1.1% ± 0.3% for the IR30 group and 7.5% ± 2.9% for the IR120 group (p < 0.05). During coronary occlusion, both the IR30 and IR120 groups demonstrated decreases in percent wall thickening in the ischemia-reperfusion zone (IRZ) as compared with the normal zone (NZ). In the IR30 group, percent wall thickening in the IRZ recovered during the reperfusion phase as compared with the NZ. In the IR120 group, percent wall thickening in the IRZ remained depressed during the reperfusion phase and through the end of the experiment as compared with the NZ. Final Tc-99m-teboroxime myocardial IRZ/NZ activity ratio was 0.94 ± 0.01 for the IR30 group, compared to 0.80 ± 0.01 for the IR120 group (p < 0.05).
Tc-99m-teboroxime demonstrates moderate differential clearance in a model of severe injury with 120 min of ischemia-reperfusion, but only minimal differential clearance in a model of mild injury with 30 min of ischemia-reperfusion. Thus, Tc-99m-teboroxime clearance kinetics may be helpful in differentiating normal and minimally injured from severely injured myocardium.
近期采用固态技术的技术发展已实现单光子发射计算机断层扫描(SPECT)的快速图像采集,并重新引发了对锝-99m-替硼肟(Tc-99m-替硼肟)作为心肌显像剂的兴趣。Tc-99m-替硼肟已显示出高心肌摄取率、即使在高血流速率下心肌摄取与血流仍呈线性关系、快速摄取和清除动力学以及在缺血情况下的差异清除。然而,此前尚未报道过Tc-99m-替硼肟在心肌损伤模型中的心肌清除动力学。因此,本研究的目的是使用犬缺血再灌注模型来(1)比较正常心肌和缺血再灌注心肌中Tc-99m-替硼肟的清除动力学,以及(2)评估Tc-99m-替硼肟清除动力学在确定缺血再灌注后损伤严重程度方面的效用。
13只犬接受左旋冠状动脉(LCx)闭塞30分钟(IR30组,n = 6)或120分钟(IR120组,n = 7),随后进行再灌注,最后在再灌注120分钟后给予Tc-99m-替硼肟。在基线、闭塞期间、再灌注后和安乐死前测定微球血流。尸检时,使用伊文思蓝染料确定危险区域面积,并使用氯化三苯基四氮唑(TTC)染色确定存活情况。然后将心脏分成24块,并在井型计数器中测量Tc-99m活性。
IR30组经TTC测定的梗死面积占左心室心肌总面积的百分比为1.1%±0.3%,IR120组为7.5%±2.9%(p < 0.05)。在冠状动脉闭塞期间,与正常区域(NZ)相比,IR30组和IR120组的缺血再灌注区域(IRZ)的壁增厚百分比均降低。在IR30组中,与NZ相比,IRZ的壁增厚百分比在再灌注阶段恢复。在IR120组中,与NZ相比,IRZ的壁增厚百分比在再灌注阶段及整个实验结束时仍降低。IR30组最终的Tc-99m-替硼肟心肌IRZ/NZ活性比值为0.94±0.01,而IR120组为0.80±0.01(p < 0.05)。
在120分钟缺血再灌注的严重损伤模型中,Tc-99m-替硼肟显示出中度差异清除,但在30分钟缺血再灌注的轻度损伤模型中仅显示出最小程度的差异清除。因此,Tc-99m-替硼肟清除动力学可能有助于区分正常心肌、轻度损伤心肌和严重损伤心肌。