Rumsey W L, Patel B, Linder K E
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA.
J Nucl Med. 1995 Apr;36(4):632-6.
The purpose of this investigation was to determine the effects of graded hypoxia on the retention of a 99mTc-labeled nitroimidazole.
Rat hearts were perfused retrogradely with Krebs-Henseleit buffer at 37 degrees C and paced at 5 Hz. After a 20-min stabilization period, coronary flow was maintained at 8 ml/min/g wet wt and the hearts were perfused with media equilibrated with gas mixtures containing 5% CO2 and various levels of O2, from 544 to 29 Torr. Technetium-99m-O(PnAO-1-(2-nitroimidazole)), BMS-181321, was infused for 20 min into a side port of the aortic cannula. Perfusion continued for an additional 40 min to allow for compound clearance.
Each decrease of perfusate PO2 brought about an increase in the retention of BMS-181321, resulting in a good correlation between its retention and perfusate PO2 (r = 0.97). Myocardial oxygen consumption was independent of oxygen delivery when the perfusate oxygen pressure was greater than 350 Torr. Below this value, oxygen consumption declined markedly as influent PO2 was decreased. By contrast, the tissue lactate/pyruvate ratio and lactate efflux rose with each decrease of influent PO2. A good correlation was obtained between retention of the nitroheterocycle and the cytosolic lactate/pyruvate ratio (r = 0.98). When glucose was omitted from the perfusate (PO2 = 27 Torr), retention of the nitroheterocycle was increased by about 25% as compared to hearts perfused in the presence of this substrate.
These results indicate that myocardial retention of BMS-181321 is coupled to the level of tissue oxygenation and that hypoxic retention may be affected by substrate input.
本研究的目的是确定分级低氧对99mTc标记的硝基咪唑滞留的影响。
将大鼠心脏在37℃下用Krebs-Henseleit缓冲液逆行灌注，并以5Hz起搏。在20分钟的稳定期后，冠状动脉流量维持在8ml/min/g湿重，并用含有5%二氧化碳和各种氧水平（从544到29托）的气体混合物平衡的培养基灌注心脏。将99mTc-O(PnAO-1-(2-硝基咪唑))，BMS-181321，注入主动脉插管的侧端口20分钟。灌注再持续40分钟以允许化合物清除。
灌注液PO2的每次降低都导致BMS-181321滞留增加，导致其滞留与灌注液PO2之间具有良好的相关性（r = 0.97）。当灌注液氧压大于350托时，心肌耗氧量与氧输送无关。低于该值时，随着流入PO2降低，耗氧量明显下降。相比之下，随着流入PO2的每次降低，组织乳酸/丙酮酸比值和乳酸流出量增加。硝基杂环的滞留与胞质乳酸/丙酮酸比值之间具有良好的相关性（r = 0.98）。当灌注液中省略葡萄糖（PO2 = 27托）时，与在该底物存在下灌注的心脏相比，硝基杂环的滞留增加约25%。
这些结果表明，BMS-181321的心肌滞留与组织氧合水平相关，并且低氧滞留可能受底物输入的影响。
