MRI STUDY ON DELAYED ANCROD THERAPY OF FOCAL CEREBRAL-ISCHEMIA IN RATS

The therapeutic window for efficient post-treatment of focal cerebral ischaemia with the fibrinogen lowering agent ancrod was studied by mag netic resonance imaging (MRI) in spontaneously hypertensive rats (SHR) . Ancrod or vehicle solution (0.9% NaCl) were i.v. infused (0.12 IU/kg per min) via implanted mini pumps starting 0.5, 1.5, 3 or 6 h after p ermanent proximal middle cerebral artery occlusion and lasting until b rain mapping by multislice T2-weighted magnetic resonance imaging in v ivo 24 h after middle cerebral artery occlusion. Plasma fibrinogen con centrations were measured before middle cerebral artery occlusion, bef ore pump implantation and after magnetic resonance imaging. Total brai n lesion volumes as determined by magnetic resonance imaging 24 h afte r middle cerebral artery occlusion were 131 +/- 36 (188 +/- 28)(), 15 1 +/- 39 (194 +/- 39)(), 147 +/- 44 (207 +/- 33)(*) and 209 +/- 60 (2 14 +/- 42) mm(3) in rats with 0.5, 1.5, 3 and 6 h, respectively, delay of ancrod treatment (means +/- S.D., 8-11 animals/group, correspondin g control groups in parentheses, P- < 0.05). Continuous i.v. ancrod i nfusions reduced plasma fibrinogen levels significantly (P < 0.05) in all ancrod-treated groups as compared to vehicle-treated controls unti l the end of the experiments 24 h after middle cerebral artery occlusi on. In conclusion, significant cerebroprotection was achieved even whe n the onset of ancrod therapy for lowering of the plasma fibrinogen le vel was delayed for up to 3 h. To the best of our knowledge no drug ef ficacy has been reported so far with a therapeutic window of 3 h after permanent middle cerebral artery occlusion in spontaneously hypertens ive rats suggesting that ancrod may provide an efficient therapy of ac ute human stroke. (C) 1997 Elsevier Science B.V.