Protective effect of intrathecal ketorolac in spinal cord ischemia in rats: a microdialysis study.
BACKGROUND
The prevention of ischemic paraplegia after thoracoabdominal aortic surgery is challenging for both anesthesiologists and surgeons. In a previous study, we showed that intrathecal ketorolac pre-treatment protects rats against ischemic spinal cord injury. In the present study, using a microdialysis method, we investigated whether this neuroprotective effect was related to changes in the spinal cord release of nitric oxide (NO) or the excitatory amino acids (EAAs) aspartate and glutamate.


METHODS
Rats were randomized to receive either intrathecal saline or ketorolac 60 microg (10 rats per group), 1 h before spinal cord ischemic injury induced by balloon inflation of a 2F Fogarty catheter in the thoracic aorta with maintenance of the proximal arterial blood pressure at 40 mmHg for 11 min, followed by reperfusion. Another 10 animals were used as the sham-operated control group. Ischemic injury was assessed by hind limb motor function. Cerebrospinal fluid dialysates were collected at baseline (before ischemia) and at 1, 2, 3, 4, 6, 12 and 24 h after the start of reperfusion, and were analyzed for EAAs using high-performance liquid chromatography and for NO metabolites using an NO analyzer.


RESULTS
The results showed that intrathecal ketorolac attenuated spinal cord ischemic injury. Dialysate concentrations of NO and EAAs were increased after spinal cord ischemia, and this effect was inhibited by intrathecal administration of ketorolac.


CONCLUSIONS
The results of this study suggest that the neuroprotective effect of intrathecal ketorolac in spinal cord ischemia in rats may be caused by a decrease in the spinal cord release of NO and EAAs.
Hsieh
Y-C
YC
Graduate Institute of Medical Science, National Defense Medical College, Neihu, Taipei, Taiwan.
Cheng
H
H
Chan
K-H
KH
Chang
W-K
WK
Liu
T-M
TM
Wong
C-S
CS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000134:cerebrospinal fluid; D007278:Injections, Spinal; D020910:Ketorolac / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis / Q000379:methods; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000134:cerebrospinal fluid / Q000517:prevention & control; D012965:Sodium Chloride / Q000008:administration & dosage; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000134:cerebrospinal fluid / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D012965:Sodium Chloride; D020910:Ketorolac