Roth S, Park S S, Sikorski C W, Osinski J, Chan R, Loomis K
Department of Anesthesia and Critical Care, University of Chicago, IL 60637, USA.
Curr Eye Res. 1997 Sep;16(9):875-85. doi: 10.1076/ceyr.16.9.875.5045.
Little is known about the nature of biochemical disturbances during reperfusion after retinal ischemia. Previous studies have suggested that adenosine is responsible for regulation of retinal blood flow soon after ischemia has ended. Therefore, in this study we measured concentrations of adenosine and its metabolites in the rat retina/choroid after brief (10 min) or prolonged (60 min) periods of ischemia, and the functional consequences of inhibiting adenosine metabolism.
Ischemia was produced in anesthetized rats by ligation of the central retinal artery. The eyes were frozen in situ and purine nucleoside concentration was determined by high performance liquid chromatography. The functional effects of pre-ischemic inhibition of xanthine dehydrogenase/xanthine oxidase were assessed by measurement of the electroretinogram before, during, and up to 7 days following 60 min ischemia.
Changes in the concentrations of adenosine and its metabolites were significant early in the reperfusion period, and were greater in magnitude and occurred earlier in prolonged, compared to brief, ischemic periods. Concentrations of adenosine, inosine, and hypoxanthine remained elevated for 30 min following the end of 60 min ischemia, and xanthine concentration was significantly elevated until 60 min after the end of either 10 or 60 min of ischemia. The onset of its peak value after ischemia was delayed in comparison to that of adenosine. Ischemia-evoked increases in xanthine concentration were attenuated by inhibition of adenosine deaminase or xanthine oxidase/xanthine dehydrogenase. Pre-ischemic inhibition of xanthine oxidase/xanthine dehydrogenase by oxypurinol (40 or 80 mg/kg intraperitoneally [IP]) resulted in a significant improvement in recovery of the a and b waves of the electroretinogram in comparison to a saline-treated control group.
These results indicate that adenosine is a major component of the biochemical changes that occur after retinal ischemia. Long-lasting increases in xanthine concentration during reperfusion after ischemia could be a source of oxygen free radicals that may contribute to delayed injury of the retina, attempts to decrease xanthine concentration would ideally be initiated within one hour after the end of ischemia.
关于视网膜缺血后再灌注期间生化紊乱的本质知之甚少。先前的研究表明，腺苷在缺血结束后不久负责调节视网膜血流。因此，在本研究中，我们测量了大鼠视网膜/脉络膜在短暂（10分钟）或长时间（60分钟）缺血后腺苷及其代谢产物的浓度，以及抑制腺苷代谢的功能后果。
通过结扎视网膜中央动脉在麻醉大鼠中诱导缺血。将眼睛原位冷冻，并用高效液相色谱法测定嘌呤核苷浓度。通过在60分钟缺血前、期间和之后长达7天测量视网膜电图，评估缺血前抑制黄嘌呤脱氢酶/黄嘌呤氧化酶的功能作用。
腺苷及其代谢产物的浓度在再灌注期早期有显著变化，与短暂缺血期相比，长时间缺血期的变化幅度更大且发生更早。在60分钟缺血结束后，腺苷、肌苷和次黄嘌呤的浓度持续升高30分钟，而黄嘌呤浓度在10或60分钟缺血结束后60分钟内显著升高。与腺苷相比，其缺血后峰值出现的时间延迟。通过抑制腺苷脱氨酶或黄嘌呤氧化酶/黄嘌呤脱氢酶，可减轻缺血引起的黄嘌呤浓度升高。与生理盐水处理的对照组相比，缺血前用氧嘌呤醇（40或80mg/kg腹腔注射[IP]）抑制黄嘌呤氧化酶/黄嘌呤脱氢酶可显著改善视网膜电图a波和b波的恢复。
这些结果表明，腺苷是视网膜缺血后发生的生化变化的主要成分。缺血后再灌注期间黄嘌呤浓度的持续升高可能是氧自由基的来源，这可能导致视网膜的延迟损伤，理想情况下应在缺血结束后一小时内开始尝试降低黄嘌呤浓度。
