SPINAL-CORD BLOOD-FLOW AFTER INTRATHECAL INJECTION OF ROPIVACAINE - ASCREENING FOR NEUROTOXIC EFFECTS

The study of spinal cord blood flow (SCBF) after spinal drug applicati on is an important aspect of preclinical neurotoxicological screening. This investigation was designed to study how a new local anesthetic, ropivacaine, affects SCBF after intrathecal (IT) administration in the rat. SCBF was measured continuously in spontaneously breathing, enflu rane/N2O-anesthetized rats, using the laser-Doppler flowmetry techniqu e. The spinal cord was exposed by laminectomy, and a laser-Doppler pro be was placed over the dorsal horn, allowing on-line registration of s pinal blood flow in a tissue hemisphere of 1-2 mm. Relative changes in spinal blood flow over time were then measured after IT administratio n of either 0.9% saline, 5 mg/mL ropivacaine, i.e., a concentration wi thin the pharmacological range, or a high, provocative concentration o f 20 mg/mL ropivacaine. A minor and transient decrease in SCBF was see n after administration of 5 mg/mL ropivacaine (50 mu g given IT), but this decrease was not significantly different from that in the saline group. SCBF decreased significantly to approximately 45% of the predru g value after the high concentration of 20 mg/mL ropivacaine (200 mu g given IT), and this reduction was reversible within a period of 20-40 min after the injection. Whereas a high concentration of ropivacaine caused a definite reduction in spinal cord blood flow when administere d IT to anesthetized rats, clinically relevant concentrations induced only minor changes. These results suggest that ropivacaine may be used to induce spinal anesthesia without causing clinically relevant effec ts on SCBF.