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Methods for the Implantation and Maintenance of Separate Intrathecal Catheters for Dose Administration and CSF Sampling in Cynomolgus Monkeys

N. Lalayeva1, N. Bailey1, G. De Los Santos1, K. Crowder1S, Glaza1, J. Morris1, R. Nagata2

Intrathecal implantation of catheters equipped with subcutaneous access ports provides the means for repeated access to cerebrospinal fluid (CSF) in the intrathecal (IT) space around the spinal cord, without the need for chemical sedation. Factors, such as catheter position or location in the IT space, can influence long-term patency and post surgical complications. Implanting a single catheter and port for both dosing and sampling increases the risk of failure and precludes the ability for concurrent sampling and dosing. IT implantation of two catheters provides capability to dose and sample from separate lines, as well as backup in case of loss of patency in either of the lines. Ten Cynomolgus monkeys were implanted with two vascular access ports and catheters via the L3-4 and L4-5 vertebral spaces. The first catheter was advanced to the vicinity of the cervico-thoracic junction and the second to the thoraco-lumbar junction. Post surgical radiography was performed following contrast media infusion into the IT space via the ports. Distance of the catheter in the IT space was determined by a combination of measuring remaining catheter post surgery and viewing the post contrast media X-ray. Post-surgery catheter maintenance was performed once weekly on non-sedated animals to verify patency of the ports and to assess the overall health and recovery of the animals. Vascular access ports were well tolerated by the animals. IT VAPs for CSF sampling were more prone to failure with loss of sampling patency being roughly 40-60% of animals within two weeks of catheter implantation.  IT VAPs for dose administration appeared to be less prone to failure (~10% of the animals within the 1st month). Length of post implantation time appeared to have an impact on catheter patency but with weekly maintenance the failure rate was reduced. In conclusion, this dual catheter technique has proven useful in allowing for separate routes of dose administration and CSF sampling via different locations within the IT space of monkeys.