Cerebral subarachnoid sampling of cerebrospinal fluid in the rhesus monkey.
A previously described rhesus monkey model with two intraventricular catheter systems was expanded to provide a means of studying drug concentrations 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 started through the lateral ventricular catheter 44 h before surgical placement of the cerebral subarachnoid catheter to allow for steady-state concentrations to be attained throughout the subarachnoid space. Monkeys were anesthetized intramuscularly with ketamine hydrochloride (7 mg/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 incision was made over the frontal bone and a 3/8-inch trephine was used to expose the dura adjacent to the lateral midline. Following puncture of the dura with an 18-gauge spinal needle, the cerebral subarachnoid catheter (0.025-inch [i.d.] x 0.047-inch [o.d.] Silastic tube) was passed 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 collected concurrently at 44, 46, and 48 h after the start of MTX infusion. Mean ventricular, lumbar subarachnoid, and cerebral subarachnoid CSF methotrexate concentrations at steady state were 5.8, 1.0, and 1.5 mumol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Veterinary Resources Program National, National Institutes of Health, Bethesda, MD 20892.
J D
JD
Bacher
F M
FM
Balis
C L
CL
McCully
K S
KS
Godwin
D000818:Animals; D002404:Catheterization / Q000379:methods; D002552:Cerebral Ventricles; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008253:Macaca mulatta; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy; D008727:Methotrexate / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D013346:Subarachnoid Space
D008727:Methotrexate