1 Department of Neurological Sciences and Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
2 Miami Cardiac and Vascular Institute and Neuroscience Center, Baptist Hospital, Miami, FL, USA.
J Cereb Blood Flow Metab. 2018 May;38(5):755-766. doi: 10.1177/0271678X17705567. Epub 2017 Apr 24.
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™ (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.
类似于慢性高血压患者，自发性高血压大鼠（SHR）在大脑中动脉闭塞（MCAO）期间会迅速发生核心进展，导致最终梗死体积较大。我们研究了 PEG 化羧基血红蛋白（COHb）气体转移剂 Sanguinate™（SG）对 MCAO 2 小时期间 SHR 侧支和再灌注脑血流变化及脑损伤的影响。SG（8ml/kg）或载体（ n = 6-8/组）在缺血 30 或 90 分钟后通过静脉内输注，随后进行 2 小时再灌注。多部位激光多普勒探头使用经过验证的方法，在缺血和再灌注期间同时测量核心 MCA 和侧支血流的变化。使用 TTC 测量脑损伤。动物用氯醛水合麻醉。与载体处理的 SHR 相比，SG 处理的动物在缺血过程中侧支血流变化较小（-8±9%vs. 输注前），而侧支血流增加（29±10%；p<0.05）。此外，SG 改善了再灌注，无论治疗时间如何；然而，与载体相比，SG 仅在早期治疗中使 SHR 的脑损伤更小（28.8±3.2%vs. 18.8±2.3%；p<0.05）。在 MCAO 期间 SHR 的有限侧支血流与小半影区和大梗死相一致。SG 增加 SHR 侧支血流的能力表明，这种化合物可能作为血管内治疗的辅助手段并延长治疗时间窗是有用的。
