CEREBRAL SUBARACHNOID SAMPLING OF CEREBROSPINAL-FLUID IN THE RHESUS-MONKEY

A previously described rhesus monkey model with two intraventricular c atheter systems was expanded to provide a means of studying drug conce ntrations of chemotherapeutic agents such as methotrexate (MTX) in the cerebral subarachnoid cerebrospinal fluid (CSF) following intrathecal drug injection. A continuous intraventricular infusion of MTX was sta rted through the lateral ventricular catheter 44 h before surgical pla cement of the cerebral subarachnoid catheter to allow for steady-state concentrations to be attained throughout the subarachnoid space. Monk eys were anesthetized intramuscularly with ketamine hydrochloride (7 m g/kg) and xylazine (6 mg/kg) to allow placement of a temporary lumbar catheter for sampling of lumbar CSF Sodium thiopental (2.5%) was given intravenously if needed for intubation and anesthesia was maintained with isoflurane (0.5 to 1.5%) and oxygen during the surgical placement and sampling of the cerebral subarachnoid catheter. A midline incisio n was made over the frontal bone and a 3/8-inch trephine was used to e xpose the dura adjacent to the lateral midline. Following puncture of the dura with an 18-gauge spinal needle, the cerebral subarachnoid cat heter (0.025-inch [i.d.] x 0.047-inch [o.d] Silastic(R) tube) was pass ed into the subarachnoid space for approximately 10 to 17 mm. The CSF from the cerebral subarachnoid catheter was collected by gravity flow Ventricular, lumbar subarachnoid, and cerebral subarachnoid CSF were c ollected concurrently at 44, 46, and 48 h after the start of MTX infus ion. Mean ventricular lumbar subarachnoid, and cerebral subarachnoid C SF methotrexate concentrations at steady state were 5.8, 1.0, and 1.5 mu mol/L, respectively. The animal model described demonstrates a succ essful means of studying drug concentrations of various drugs such as MTX throughout the CSF space during continuous intraventricular infusi ons.