[The advantages of associating ischemia/reperfusion injury inhibitors with intravenous thrombolysis when treating focal brain ischemia: a description of experiments using rats].
Restoration of blood flow is necessary when treating brain ischemia. However, except in very early cases, this is insufficient to prevent the cascade of mediators of cell damage unleashed by ischemia which, on the other hand, is boosted by the deleterious effects of reperfusion. We therefore consider adequate treatment for brain ischemia ought to associate, early on, reperfusion with pharmacological inhibition of those intermediaries in damage caused by ischemia/reperfusion (cytoprotection), basically an excess of cytosolic calcium and of free radicals. In this way, spreading of the infarct may be avoided more effectively than just with reperfusion alone. Our aim was to demonstrate this hypothesis using an experimental model. In order to do so, we shall embolize the right carotid artery territory of 50 Long Evans rats with autologous blood thrombi and check the location of the embolus using arteriography. Forty rats will receive thrombolytic treatment intravenously (rTPA at a dose of 20 mg/kg) two hours after embolization, while 10 control rats will receive similar treatment with saline serum. The thrombolysis treated animal group will be divided into four subgroups (A, B, C, D, ni = 10). Group A will be considered as the thrombolysis control group; group B will additionally receive calcium antagonists (dihydropyridines); group C will undergo antioxidant treatment (21-aminosteroids) and group D both calcium antagonists and antioxidants in association with thrombolysis. The size of infarct produced in each group, estimated following Cavalieri's principle, will be compared using nonparametric statistical tests (Mann-Whitney test and Willcoxon test). We present the preliminary results so obtained in a group of 14 control rats studied with the aim of assessing the usefulness of the proposed model.
Alonso de Leciñana
M
M
Unidad de Investigación Cerebrovascular, Hospital Universitario La Paz, Universidad Autónoma, Madrid.
Díez-Tejedor
E
E
Carceller
F
F
Vega
A
A
Roda
J M
JM
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals; D008297:Male; D051381:Rats
D000975:Antioxidants; D002121:Calcium Channel Blockers; D005343:Fibrinolytic Agents; D005609:Free Radicals
Ventajas de asociar inhibidores del daño por isquemia/reperfusión a la trombólisis intravenosa en el tratamiento de la isquemia cerebral focal. Descripción de un modelo experimental en ratas.