Gidday J M, Zhu Y
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Curr Eye Res. 1998 Aug;17(8):798-807.
Little is known regarding the status and implications of altered retinal blood flow (RBF) following a period of temporary retinal ischemia. We undertook studies to measure acute changes in RBF after ischemia, and the mechanisms responsible for mediating these changes.
Retinal ischemia was induced in anesthetized, mechanically ventilated newborn pigs by severe hypoxia, hypotension, and bradycardia secondary to 9 min of asphyxia by discontinued ventilation. Using fluorescein videoangiography, we calculated stimulus-induced changes in RBF by measuring changes in arteriovenous transit times and arteriolar and venular diameters from the angiogram videorecordings.
Asphyxia led to a progressive reduction in RBF during early reperfusion, with RBF decreasing 24 +/- 6% and 34 +/- 5% below baseline 1 h and 2 h, respectively, after asphyxia (n = 6). Intravitreal administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (25 nmol) at 15 min of postischemic reperfusion did not increase the magnitude of hypoperfusion (n = 6), and intravitreal acetylcholine (20 nmol) was no longer able to increase RBF at 1.5-2.0 h of postasphyxic reperfusion. The endothelin A receptor antagonist TBC 11251z attenuated the response by 53% at 2 h (n = 5). The adenosine transport inhibitor 4-nitrobenzyl-6-thioinosine reversed the hypoperfusion response (n = 5), whereas ventilating animals with 100% oxygen during reperfusion exacerbated the flow deficit, with RBF reduced to 49 +/- 5% below baseline at 2 h post-asphyxia (n = 6).
These findings indicate that (1) constriction by endothelin, together with a loss of nitric oxide's tonic dilatative effect, contributes importantly to mediating postischemic hypoperfusion in retina; (2) improvements in retinal perfusion can be realized with endothelin receptor blockade or potentiation of extracellular adenosine; and (3) additional reductions in postischemic RBF can occur in response to resuscitation with 100% oxygen because retinal microcirculatory reactivity to hyperoxia remains intact during the hypoperfusion period.
关于短暂性视网膜缺血一段时间后视网膜血流（RBF）改变的状态及影响，目前所知甚少。我们开展了研究以测量缺血后RBF的急性变化，以及介导这些变化的机制。
通过停止通气9分钟导致窒息继发严重缺氧、低血压和心动过缓，在麻醉、机械通气的新生猪中诱导视网膜缺血。使用荧光素视频血管造影术，我们通过测量血管造影视频记录中的动静脉 transit 时间以及小动脉和小静脉直径的变化，计算刺激诱导的RBF变化。
窒息导致再灌注早期RBF逐渐降低，窒息后1小时和2小时，RBF分别降至基线以下24±6%和34±5%（n = 6）。缺血后再灌注15分钟时玻璃体内注射一氧化氮合酶抑制剂NG-单甲基-L-精氨酸（25 nmol）并未增加低灌注的程度（n = 6），窒息后再灌注1.5 - 2.0小时时玻璃体内注射乙酰胆碱（20 nmol）不再能够增加RBF。内皮素A受体拮抗剂TBC 11251z在2小时时使反应减弱了53%（n = 5）。腺苷转运抑制剂4-硝基苄基-6-硫代肌苷逆转了低灌注反应（n = 5），而在再灌注期间用100%氧气对动物进行通气会加剧血流不足，窒息后2小时RBF降至基线以下49±5%（n = 6）。
这些发现表明：（1）内皮素收缩以及一氧化氮张力性舒张作用丧失对介导视网膜缺血后低灌注起重要作用；（2）通过内皮素受体阻断或增强细胞外腺苷可实现视网膜灌注改善；（3）由于在低灌注期视网膜微循环对高氧的反应性保持完整，用100%氧气复苏会导致缺血后RBF进一步降低。
