Morphological changes in acute focal ischemia: response to osmotherapy

The sequential morphological changes following acute MCA occlusion in conscious cats were studied. The artery was occluded with a simple implanted device that resulted in immediate contralateral hemiparesis. The ischemic changes in the MCA territory developed in a diphasic fashion. Astrocytic swelling and capillary narrowing preceded the development of ischemic neuronal alterations during the primary phase. Capillary obstruction developed during the secondary phase when tissue injury was advanced. Increased vascular permeability to fluorescein was seen with 90 min of MCA occlusion and was initially confined to ischemic gray matter. Leakage of fluorescein consistently occurred with occlusion periods of 90 min and longer, whereas increased permeability to Evans blue was transient. A single, standard dose of mannitol (1.0 to 1.2 g/kg i.v.) was shown to improve the neurological deficit and delay the onset of ischemic injury. Considerable preservation of cerebral tissue was demonstrated with ischemic periods up to 6 hr. The administration of small (0.5 g/kg i.v.), repeated doses of mannitol was found to prolong the beneficial effects.