Abstract
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.
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