Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.

Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.
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血红蛋白氧亲和力的合成变构调节剂对大鼠全脑缺血结果的影响。

DOI:
10.1161/01.str.29.8.1650
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发表时间:
1998
期刊:
影响因子:
8.3
通讯作者:
Warner,DS
Warner,DS
中科院分区:
医学1区
文献类型:
--
作者:
Grocott,HP;Bart,RD;Sheng,H;Miura,Y;Steffen,R;Pearlstein,RD;Warner,DS

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背景和目的——神经损伤是由于大脑供氧不足造成的。本实验检验了药理诱导的氧分压右移(50% 血红蛋白饱和 (P50))是否会改善大鼠不完全和/或接近完全前脑缺血引起的缺氧的结果。方法 - 对于不完全缺血(减弱脑电图),禁食大鼠(每组 n = 17 至 19)给予血红蛋白对氧亲和力的合成变构调节剂(RSR13;150 mg/kg IV)在双侧颈动脉闭塞 20 分钟之前或之后立即服用,同时平均动脉压降低至 40 mm Hg。对于接近完全缺血(等电脑电图),大鼠(每组 15 只)在双侧颈动脉闭塞 10 分钟后再灌注开始时给予 RSR13(150 mg/kg),同时平均动脉压降低至 30 mm Hg。在这两个实验中,对照大鼠仅给予媒介物(0.9% NaCl IV)。缺血后 5 天确定结果(定义为死亡海马 CA1 神经元百分比)。结果 — RSR13 (150 mg/kg) 产生 68% 的 P50 右移(34±3 至 57±8 mm Hg)。 RSR13 可使不完全缺血引起的 CA1 损伤降低 28% (P=0.02),但仅在再灌注开始时给药。 RSR13 对近完全缺血的结果没有影响。结论——缺血后药物诱导的 P50 增加可能会改善不完全性全脑缺血的结果。更严重(接近完全)的缺血会抵消这种益处。
Background and Purpose—Neuronal injury results from an insufficient supply of oxygen to the brain. This experiment examined whether a pharmacologically induced rightward shift of the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) would improve outcome from either incomplete and/or near-complete forebrain ischemia–induced hypoxia in the rat.Methods—For incomplete ischemia (attenuated electroencephalogram), fasted rats (n=17 to 19 per group) were given a synthetic allosteric modifier of hemoglobin affinity for oxygen (RSR13; 150 mg/kg IV) before or immediately after 20 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 40 mm Hg. For near-complete ischemia (isoelectric electroencephalogram), rats (n=15 per group) were given RSR13 (150 mg/kg) at onset of reperfusion after 10 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 30 mm Hg. In both experiments, control rats were given vehicle (0.9% NaCl IV) only. Outcome (defined as percent dead hippocampal CA1 neurons) was determined at 5 days after ischemia.Results—RSR13 (150 mg/kg) produced a 68% rightward shift of P50 (34±3 to 57±8 mm Hg). RSR13 reduced CA1 damage resulting from incomplete ischemia by 28% (P=0.02), but only when administered at the onset of reperfusion. RSR13 had no effect on outcome from near-complete ischemia.Conclusions—A postischemic pharmacologically induced increase in P50 may improve outcome from incomplete global cerebral ischemia. More severe (near-complete) ischemia negates this benefit.
血红蛋白氧饱和度的局部变化对缺氧和低血压引起的脑血管舒张的影响。
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