Spinal cord blood flow after intrathecal injection of ropivacaine: a screening for neurotoxic effects.
The study of spinal cord blood flow (SCBF) after spinal drug application 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, enflurane/N2O-anesthetized rats, using the laser-Doppler flowmetry technique. The spinal cord was exposed by laminectomy, and a laser-Doppler probe was placed over the dorsal horn, allowing on-line registration of spinal blood flow in a tissue hemisphere of 1-2 mm. Relative changes in spinal blood flow over time were then measured after IT administration of either 0.9% saline, 5 mg/mL ropivacaine, i.e., a concentration within the pharmacological range, or a high, provocative concentration of 20 mg/mL ropivacaine. A minor and transient decrease in SCBF was seen after administration of 5 mg/mL ropivacaine (50 micrograms given IT), but this decrease was not significantly different from that in the saline group. SCBF decreased significantly to approximately 45% of the predrug value after the high concentration of 20 mg/mL ropivacaine (200 micrograms 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 administered 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 effects on SCBF.
Kristensen
J D
JD
Department of Anesthesiology and Intensive Care, University Hospital, Uppsala, Sweden.
Karlsten
R
R
Gordh
T
T
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000775:Anesthesia, Spinal; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide; D004737:Enflurane / Q000008:administration & dosage; D007278:Injections, Spinal; D007796:Laminectomy; D017078:Laser-Doppler Flowmetry; D008297:Male; D009609:Nitrous Oxide / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000077212:Ropivacaine; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects*; D013997:Time Factors
D000577:Amides; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D002245:Carbon Dioxide; D000077212:Ropivacaine; D004737:Enflurane; D009609:Nitrous Oxide