Moore C A, Cannon J, Watson D D, Kaul S, Beller G A
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Circulation. 1990 May;81(5):1622-32. doi: 10.1161/01.cir.81.5.1622.
The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible.
本研究检验的假设是,尽管存在严重的缺血后心肌功能障碍(“心肌顿抑”),但只要避免不可逆的肌膜损伤,铊201的摄取及随后的细胞内洗脱就应保持正常。为产生心肌顿抑,19只开胸的患有严重左前降支冠状动脉(LAD)狭窄的犬,经历了10次每次5分钟的LAD完全闭塞,每次闭塞之间间隔10分钟通过严重狭窄处的再灌注。在另外12只在相同时间段观察的对照犬中,放置严重狭窄后未进行LAD闭塞。连续测量血流动力学、通过定量二维超声心动图测量的局部心肌增厚以及微球测定的局部血流。在18只顿抑犬中,第10次再灌注期后40分钟,LAD区域的收缩期增厚显著降低至0.4±2.4%,而12只对照犬在相同时刻的增厚为32.5±2.2%(p<0.001)。在一组13只顿抑犬和6只对照犬的亚组中,第10次再灌注后通过冠状动脉内注射铊201采用双同位素法测定的铊201首次通过摄取分数相当(顿抑犬为0.78,对照犬为0.79)。在另一组6只顿抑犬(60±13分钟)和6只对照犬(53±14分钟)中,细胞内洗脱率的半衰期也无显著差异,最初分布在间质腔室的铊201剂量百分比也无差异(分别为11±3%和7±2%)。第10次再灌注后40分钟,两组的全身血流动力学和局部血流相当。通过氯化三苯基四氮唑染色,没有犬出现心肌坏死的证据。因此,在由重复性短暂LAD闭塞产生的严重缺血后功能障碍(顿抑)的犬模型中,观察到正常的心肌铊201摄取和洗脱动力学。这些发现可能对静息铊201闪烁显像在评估冠状动脉疾病患者的灌注和存活能力以及最终可逆的局部心肌协同失调方面的应用具有重要的临床意义。