ORIGINAL ARTICLES  CARDIAC SECTION 

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

Copyright © 2009 EDIZIONI MINERVA MEDICA

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%.