Bacher J D, Balis F M, McCully C L, Godwin K S
Veterinary Resources Program National, National Institutes of Health, Bethesda, MD 20892.
Lab Anim Sci. 1994 Apr;44(2):148-52.
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)
一个先前描述的带有两个脑室内导管系统的恒河猴模型得到扩展,以提供一种在鞘内注射药物后研究脑蛛网膜下腔脑脊液(CSF)中诸如甲氨蝶呤(MTX)等化疗药物浓度的方法。在手术放置脑蛛网膜下腔导管前44小时,通过侧脑室导管开始持续脑室内输注MTX,以使整个蛛网膜下腔达到稳态浓度。用盐酸氯胺酮(7mg/kg)和赛拉嗪(6mg/kg)肌肉注射麻醉猴子,以便放置临时腰段导管采集腰段CSF。如有必要,静脉注射硫喷妥钠(2.5%)用于插管,并在手术放置和采集脑蛛网膜下腔导管期间用异氟烷(0.5%至1.5%)和氧气维持麻醉。在额骨上做一个中线切口,用一个3/8英寸的环钻暴露外侧中线附近的硬脑膜。用18号脊髓穿刺针穿刺硬脑膜后,将脑蛛网膜下腔导管(内径0.025英寸×外径0.047英寸的硅橡胶管)插入蛛网膜下腔约10至17毫米。通过重力引流收集脑蛛网膜下腔导管中的CSF。在MTX输注开始后44、46和48小时同时采集脑室、腰段蛛网膜下腔和脑蛛网膜下腔的CSF。稳态时脑室、腰段蛛网膜下腔和脑蛛网膜下腔CSF中甲氨蝶呤的平均浓度分别为5.8、1.0和1.5μmol/L。(摘要截短于250字)