The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent.
BACKGROUND
Chlorpromazine (CPZ), at high doses, has been shown to protect the central nervous system in experimental models of ischemia and reperfusion. The purpose of this study was: 1) to investigate the protection afforded by different doses of CPZ on the spinal cord of rabbits submitted to ischemia and reperfusion. 2) to correlate the motor impairment of the hind limbs and the percentage of damaged neurons in the anterior horns of the lumbar spinal cord in treated and untreated animals.


METHODS
Seventy-two New Zealand white rabbits were divided into 6 equal groups (n=12): sham operation, control and 4 study groups. Spinal cord ischemia was obtained by clamping the abdominal aorta caudally to the renal arteries for 30 min, after which it was released and the animals were observed for a period of 48 hrs. The control animals received 3 ml/kg of 0.9% NaCl, i.v., 10 min before aorta clamping. The experimental animals received CPZ, i.v., at doses of 2, 1 and 0.5 mg/kg, 10 min before aorta clamping. In one group 1 mg/kg of CPZ was given 10 min before aorta clamping and the same dose was repeated 2 hrs after the beginning of reperfusion. The spinal cord of the control animals and of those who received one CPZ dose of 2 mg/kg was processed for light microscopy examination.


RESULTS
Motor scores of the hind limbs, graded 0 to 4, obtained 48 hrs after the beginning of reperfusion showed that CPZ was effective at doses of 2 and 1 mg/kg. No significant difference was observed with the dose of 0.5 mg/kg. However, the best results were obtained with the dose of 2 mg/kg administered in a fractionated manner. Histological examination revealed that at the dose of 2 mg/kg, CPZ protected a significant number of neuronal cells and that motor recovery hardly occurred when the number of damaged neurons exceeded 50%.


CONCLUSIONS
1) The neuroprotective action of CPZ is dose-dependent in the ischemic spinal cord of rabbits. The lower protective dose is 1 mg/kg, which is too high for human beings. 2) There is an inverse correlation between motor recovery and percentage of damaged neurons, and the critical point seems to be between 30% and 50%.
Sader
A Amin
AA
Laboratory of Experimental Surgery, Department of Surgery, Ribeirão Preto School of Medical Sciences, University of São Paulo, São Paulo, Brazil.
Barbieri-Neto
J
J
Sader
S Lopes
SL
Mazzetto
S Assis
SA
Alves
P
P
Vanni
J C
JC
D000818:Animals; D001707:Biopsy, Needle; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002746:Chlorpromazine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000473:pathology*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D002746:Chlorpromazine