Laser-Doppler evaluation of spinal cord blood flow after intrathecal administration of an N-methyl-D-aspartate antagonist in rats.
The N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), which produces antinociception in experimental animal models after spinal administration, may be of value in clinical pain treatment. Safety screening of drugs intended for spinal administration includes evaluation of the drug's effect on spinal cord blood flow (SCBF). In the present study, laser-Doppler flowmetry technique was used to assess SCBF in an experimental model using anesthetized, spontaneously breathing rats. Methodologic aspects of the experimental set-up were studied, and the effects on SCBF were evaluated after intrathecal (IT) administration of saline or CPP in a dose range of 1-100 nmol. The spontaneously breathing rats, anesthetized with enflurane/N2O had stable mean arterial blood pressure values throughout the study, and no difference was found in arterial blood gas values or acid-base status measured either before or after the 80-min observation period. A reproducible increase in SCBF of approximately 10% during an 80-min measuring period was found in saline-treated rats. The trauma of the IT injection procedure gave a disturbance in the registered SCBF that lasted less than 10 min. No difference was found in SCBF between rats injected IT with either saline or CPP in a dose range from 1 nmol, i.e., a pharmacologically active dose, to 100 nmol, i.e., a provocative dose 400-fold the smallest dose that produces antinociception. When acidic solutions were injected, the SCBF increased in inverse proportion to pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Kristensen
J D
JD
Department of Anaesthesiology and Intensive Care, University Hospital, Uppsala, Sweden.
Karlsten
R
R
Gordh
T
T
D000818:Animals; D017078:Laser-Doppler Flowmetry; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000098:blood supply*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid