Okada R D, Nguyen K N, Strauss H W, Johnson G
William K. Warren Medical Research Institute of the University of Oklahoma Health Sciences Center, Tulsa, USA.
Eur J Nucl Med. 1996 Apr;23(4):443-7. doi: 10.1007/BF01247374.
The purpose of the present study was to determine whether graded levels of low-flow ischemia would lead to graded differences in uptake and clearance of BMS181321. Using a perfused rat heart model, 7.4 MBq (200 microCi) of BMS181321 was infused over 20 min, followed by a 60-min clearance phase. Activity was monitored using an NaI detector. Four groups were studied using Krebs-Henseleit buffer perfusion using low flow or hypoxia: group 1=12 ml/min, group 2=3 ml/min, and group 3=1 ml/min during uptake and clearance phases, and group 4=12 ml/min with hypoxia during clearance. Control and low-flow groups were also perfused using red blood cells and albumin. There was a stepwise increase in peak myocardial uptake (% injected dose) as flow progressively decreased (group 1=2.4%+/-0.2% SEM, group 2=13.1%+/-0.7%, group 3=28.6%+/-2.4%, P <0.05). Group 3/group 1 mean peak activity ratio was 12:1. Mean 1-h fractional retention significantly increased in a stepwise manner as flow decreased (group 1=0.32+/-0.02, group 2=0.43+/-0.03, group 3=0.59+/-0.05, P <0.05). Group 3/group 1 mean 1-h clearance activity ratio was 30:1. Groups 5 and 6 perfused with red blood cells and albumin demonstrated similar increases in peak uptake and 1-h retention in the low-flow hearts. This study demonstrates a stepwise increase in uptake and a stepwise increase in retention rate of BMS181321 with progressive reduction in flow.
本研究的目的是确定低流量缺血的分级水平是否会导致BMS181321摄取和清除的分级差异。使用灌注大鼠心脏模型，在20分钟内注入7.4 MBq（200微居里）的BMS181321，随后是60分钟的清除期。使用NaI探测器监测活性。使用低流量或缺氧的Krebs-Henseleit缓冲液灌注研究了四组：第1组在摄取和清除期为12 ml/min，第2组为3 ml/min，第3组为1 ml/min，第4组在清除期为12 ml/min并伴有缺氧。对照组和低流量组也使用红细胞和白蛋白进行灌注。随着流量逐渐降低，心肌摄取峰值（注射剂量百分比）呈逐步增加（第1组=2.4%±0.2% SEM，第2组=13.1%±0.7%，第3组=28.6%±2.4%，P<0.05）。第3组/第1组的平均峰值活性比为12:1。随着流量降低，平均1小时分数滞留率显著逐步增加（第1组=0.32±0.02，第2组=0.43±0.03，第3组=0.59±0.05，P<0.05）。第3组/第1组的平均1小时清除活性比为30:1。用红细胞和白蛋白灌注的第5组和第6组在低流量心脏中显示出类似的峰值摄取增加和1小时滞留增加。本研究表明，随着流量逐渐降低，BMS181321的摄取逐步增加，滞留率也逐步增加。
