VENTRICULAR DILATATION IN EXPERIMENTAL INTRAVENTRICULAR HEMORRHAGE INPIGS - CHARACTERIZATION OF CEREBROSPINAL-FLUID DYNAMICS AND THE EFFECTS OF FIBRINOLYTIC TREATMENT

Background and Purpose Hemorrhagic ventricular dilatation (HVD) is a p rominent feature of human intraventricular hemorrhage (IVH) and a stro ng indicator for poor outcome. We developed an IVH model to define the mechanisms responsible for HVD and to test the efficacy of intraventr icular administration of tissue plasminogen activator (TPA) in the tre atment of HVD. Methods Isolated IVH was produced in pigs by injecting 10 mL of blood simultaneously with thrombin into the right lateral ven tricle. The treatment group received 1.5 mg of TPA after induction of IVH. Intraventricular blood volume and the volume of the lateral ventr icles were assessed by CT after 90 minutes, 7 days, and 42 days. Intra cranial pressure, the pressure-volume index, and the resistance to out flow of cerebrospinal fluid R(out)) were measured 30 minutes and 7 day s after IVH. Results After IVH, the volume of the lateral ventricles i ncreased from 1.98+/-0.69 to 6.43+/-1.23 mL (P<.001). There was a line ar relationship between ventricular and clot volume (P=.014). Initiall y, R(out) increased from 24.34+/-7.13 to 63.56+/-64.91 mm Hg/mL per mi nute (P<.001). After 7 days, restoration of normal cerebrospinal fluid circulation occurred, but the ventricles were still significantly enl arged (5.24+/-1.76 mL, P<.001) and filled with blood. Within 6 weeks, ventricular volume had returned to normal values, paralleled by comple te clot resolution. Intraventricular administration of TPA significant ly accelerated clot clearance and restoration of normal ventricle volu me. Conclusions These results suggest that intraventricular bleeding m ay cause impairment of cerebrospinal fluid circulation but that the ma ss effect of clots distending the ventricle walls is the most importan t mechanism responsible for HVD. This model closely imitates several p rominent features of human IVH and may therefore be a useful tool for preclinical assessment of the efficacy and safety of treatment with TP A.