Mayfrank L, Kissler J, Raoofi R, Delsing P, Weis J, Küker W, Gilsbach J M
Department of Neurosurgery, Medical Faculty of the University of Technology (RWTH), Aachen, Germany.
Stroke. 1997 Jan;28(1):141-8. doi: 10.1161/01.str.28.1.141.
Hemorrhagic ventricular dilatation (HVD) is a prominent feature of human intraventricular hemorrhage (IVH) and a strong indicator for poor outcome. We developed an IVH model to define the mechanisms responsible for HVD and to test the efficacy of intraventricular administration of tissue plasminogen activator (TPA) in the treatment of HVD.
Isolated IVH was produced in pigs by injecting 10 mL of blood simultaneously with thrombin into the right lateral ventricle. The treatment group received 1.5 mg of TPA after induction of IVH. Intraventricular blood volume and the volume of the lateral ventricles were assessed by CT after 90 minutes, 7 days, and 42 days. Intracranial pressure, the pressure-volume index, and the resistance to outflow of cerebrospinal fluid (R(out)) were measured 30 minutes and 7 days after IVH.
After IVH, the volume of the lateral ventricles increased from 1.98 +/- 0.69 to 6.43 +/- 1.23 mL (P < .001). There was a linear relationship between ventricular and clot volume (P = .014). Initially, R(out) increased from 24.34 +/- 7.13 to 63.56 +/- 64.91 mm Hg/mL per minute (P < .001). After 7 days, restoration of normal cerebrospinal fluid circulation occurred, but the ventricles were still significantly enlarged (5.24 +/- 1.76 mL, P < .001) and filled with blood. Within 6 weeks, ventricular volume had returned to normal values, paralleled by complete clot resolution. Intraventricular administration of TPA significantly accelerated clot clearance and restoration of normal ventricle volume.
These results suggest that intraventricular bleeding may cause impairment of cerebrospinal fluid circulation but that the mass effect of clots distending the ventricle walls is the most important mechanism responsible for HVD. This model closely imitates several prominent features of human IVH and may therefore be a useful tool for preclinical assessment of the efficacy and safety of treatment with TPA.
出血性脑室扩张（HVD）是人类脑室内出血（IVH）的一个显著特征，也是预后不良的一个有力指标。我们建立了一个IVH模型，以确定导致HVD的机制，并测试脑室内注射组织型纤溶酶原激活剂（TPA）治疗HVD的疗效。
通过将10 mL血液与凝血酶同时注入猪的右侧脑室，制造孤立性IVH。治疗组在IVH诱导后接受1.5 mg TPA。在90分钟、7天和42天后通过CT评估脑室内血量和侧脑室体积。在IVH后30分钟和7天测量颅内压、压力-容积指数和脑脊液流出阻力（R(out)）。
IVH后，侧脑室体积从1.98±0.69 mL增加到6.43±1.23 mL（P<.001）。脑室与血凝块体积之间存在线性关系（P=.014）。最初，R(out)从24.34±7.13增加到63.56±64.91 mmHg/mL每分钟（P<.001）。7天后，脑脊液循环恢复正常，但脑室仍明显扩大（5.24±1.76 mL，P<.001）且充满血液。在6周内，脑室体积恢复到正常水平，同时血凝块完全溶解。脑室内注射TPA显著加速了血凝块清除和脑室体积恢复正常。
这些结果表明，脑室内出血可能导致脑脊液循环障碍，但血凝块扩张脑室壁的占位效应是导致HVD的最重要机制。该模型紧密模仿了人类IVH的几个显著特征，因此可能是临床前评估TPA治疗疗效和安全性的有用工具。
