Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues

Introduction: Neuropharmacology studies depend on consistency in drug delivery. Drug infusions into central nervous system (CNS) tissues have been described as unreliable. Speculation has focused on infusion pumps as the source of variation. This report demonstrates that the catheter may be a source of variability. The inconsistency can be significantly reduced by a change in catheter design. Methods: Normal and tumor cell-challenged (abnormal) brains of Fischer rats were infused with small and large molecular weight cytotoxic drugs via rigid and flexible catheters placed directly into the parenchyma. Coronal tissue sections rostral and caudal to the infusion point were analyzed for drug concentrations. Carboplatin, estimated through atomic absorption assays, and doxorubicin and transferrin-bound doxorubicin, measured by fluorescent spectroscopy, were mapped in serial sections at various distances from the infusion point. Results: The expected drug distribution pattern approximates a bell-shaped curve with a maximum drug concentration near the infusion point and approximately equal, declining concentrations rostral and caudal to the infusion. This expected distribution was found in only 10 of the 17 normal brains and 15 of the 28 abnormal brains infused with a rigid catheter. In contrast, 10 of the 10 normal brains and 16 of the 16 abnormal rat brains infused with a flexible catheter had the expected distribution pattern. The distribution pattern was not associated with the molecular weight of the infused drug. Conclusion: Replacement of rigid infusion tubes with flexible tubing increases the reliability of local CNS drug infusions. Rigid catheters may allow backflow of the infused drug along the path of the catheters into the subdural space.