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The Journal of Cardiovascular Surgery 2002 December;43(6):827-31

lingua: Inglese

The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent

Amin Sader A., Barbieri-Neto J., Lopes Sader S., Assis Mazzetto S., Alves P. Jr., Vanni J. C.

Labor­a­tory of Experi­mental Sur­gery Depart­ments of Sur­gery and ­Pathology Ribeirão ­Preto ­School of Med­ical Sci­ences Uni­ver­sity of São ­Paulo, ­São Paulo, Brazil


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, iv, 10 min ­before ­aorta ­clamping. The experi­mental ani­mals ­received CPZ, iv, 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%.

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