From the Neurovascular Research Laboratory, Department of Radiology (F.S., M.B., T.Q., I.T., P.F., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.
Stroke Research Center (F.S., G.B., S.M.G.), Massachusetts General Hospital, Harvard Medical School, Boston.
Stroke. 2019 May;50(5):1210-1215. doi: 10.1161/STROKEAHA.118.021732.
Background and Purpose- Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth. Methods- To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection. Results- Secondary hemorrhage occurred in a volume-dependent (4, 7.5, or 15 μL of polymer) and rate-dependent (0.05, 0.5, or 5 μL/s) manner. Anticoagulation (warfarin or dabigatran) exacerbated the secondary hemorrhage volume. In a second model of hematoma expansion, we confirmed that intrastriatal whole blood injection (15 μL, 0.5 μL/s) also caused secondary bleeding, using acute Evans blue extravasation as a surrogate. Anticoagulation once again exacerbated secondary hemorrhage after intrastriatal whole blood injection. Secondary hemorrhage directly and significantly correlated with arterial blood pressures in both nonanticoagulated and anticoagulated mice, when modulated by phenylephrine or labetalol. Conclusions- Our study provides the first proof of concept for secondary vessel rupture and bleeding as a potential mechanism for intracerebral hematoma growth.
背景与目的- 导致脑出血中急性血肿增长的机制尚不清楚。神经病理学研究表明，最初的血肿可能会通过剪切造成局部血管破裂，导致进一步出血和血肿增大。方法- 为了在小鼠中验证这一点，我们通过向纹状体内部注射一种液体聚合物来模拟初始的脑出血，这种聚合物在与组织接触时会凝固，并在注射后 15 分钟使用血红蛋白 ELISA 测量继发于质量效应的出血的存在和体积。结果- 继发性出血呈体积依赖性（4、7.5 或 15 μL 聚合物）和速率依赖性（0.05、0.5 或 5 μL/s）。抗凝（华法林或达比加群）加重了继发性出血的体积。在血肿扩大的第二个模型中，我们通过急性 Evans 蓝外渗作为替代物证实，向纹状体内部注射全血（15 μL，0.5 μL/s）也会导致继发性出血。抗凝再次加重了向纹状体内部注射全血后的继发性出血。在未抗凝和抗凝的小鼠中，继发性出血与动脉血压直接且显著相关，可通过苯肾上腺素或拉贝洛尔进行调节。结论- 我们的研究首次提供了继发性血管破裂和出血作为脑出血增长潜在机制的概念验证。
