Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats
Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats
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DOI：
10.1177/0271678x17705567
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发表时间：
2018-05-01
影响因子：
6.3
通讯作者：
Chan, Siu-Lung
中科院分区：
文献类型：
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作者：
Cipolla, Marilyn J.;Linfante, Italo;Chan, Siu-Lung
与慢性高血压患者类似，自发性高血压大鼠（SHR）在大脑中动脉闭塞（MCAO）期间出现快速核心进展，导致最终梗塞体积较大。我们研究了血红蛋白 (TM) (SG)（一种聚乙二醇化碳氧血红蛋白 (COHb) 气体转移剂）对 MCAO 2 小时期间 SHR 侧支和再灌注脑血流变化以及脑损伤的影响。静脉注射 SG (8 mL/kg) 或载体（n = 6-8/组）。缺血 30 或 90 分钟后再灌注 2 小时。多部位激光多普勒探头使用经过验证的方法同时测量缺血和再灌注期间核心 MCA 和侧支血流的变化。使用 TTC 测量脑损伤。用水合合唱团麻醉动物。在缺血期间，经载体治疗的 SHR 的侧支血流变化很小（-8 +/- 9% 与输注前相比），而经 SG 治疗的动物的侧支血流增加（29 +/- 10%；p < 0.05）。此外，无论治疗时间如何，SG 都能改善再灌注；然而，与媒介物相比，只有在 SHR 早期治疗的情况下，脑损伤才会更小（28.8 +/- 3.2% 对比 18.8 +/- 2.3%；p < 0.05）。 MCAO 期间 SHR 侧支血流有限与小半暗带和大梗塞一致。 SG 增加 SHR 侧支血流的能力表明，该化合物可用作血管内治疗的辅助手段并延长治疗时间窗。
Similar to patients with chronic hypertension, spontaneously hypertensive rats (SHR) develop fast core progression during middle cerebral artery occlusion (MCAO) resulting in large final infarct volumes. We investigated the effect of Sanguinate (TM) (SG), a PEGylated carboxyhemoglobin (COHb) gas transfer agent, on changes in collateral and reperfusion cerebral blood flow and brain injury in SHR during 2 h of MCAO. SG (8 mL/kg) or vehicle (n = 6-8/group) was infused i.v. after 30 or 90 min of ischemia with 2 h reperfusion. Multi-site laser Doppler probes simultaneously measured changes in core MCA and collateral flow during ischemia and reperfusion using a validated method. Brain injury was measured using TTC. Animals were anesthetized with choral hydrate. Collateral flow changed little in vehicle-treated SHR during ischemia (-8 +/- 9% vs. prior to infusion) whereas flow increased in SG-treated animals (29 +/- 10%; p < 0.05). In addition, SG improved reperfusion regardless of time of treatment; however, brain injury was smaller only with early treatment in SHR vs. vehicle (28.8 +/- 3.2% vs. 18.8 +/- 2.3%; p < 0.05). Limited collateral flow in SHR during MCAO is consistent with small penumbra and large infarction. The ability to increase collateral flow in SHR with SG suggests that this compound may be useful as an adjunct to endovascular therapy and extend the time window for treatment.