Modification of acute focal ischemia by treatment with mannitol and high-dose dexamethasone.
A simple implanted device was used to occlude the left middle cerebral artery (MCA) of 50 conscious cats. In the acute experiments, 10 cats were given mannitol (1.2 gm/kg intravenously) and 10 cats were untreated. The neurological status of the treated cats improved. Perfusion with a mixture of colloidal carbon and buffered paraformaldehyde was carried out from 30 minutes to 12 hours following MCA occlusion. Results of the morphological examination of the brains demonstrated that mannitol delayed the development of neuronal alterations and edema. Measurement of capillary luminal diameters in the ischemic cortex of the untreated cats revealed progressive narrowing with microcirculatory obstruction occurring at 6 hours. Capillary narrowing was absent or minimal in the treated cats during the initial 6 hours. Breakdown of the blood-brain barrier also was delayed by treatment. In the 30 subacute experiments, 10 cats were untreated, 10 cats received mannitol (1.2 gm/kg intravenously), and 10 cats were given a combination of mannitol and high-dose dexamethasone. Although early transient clinical improvement occurred in the treated animals, morphological findings in the brains of the treated and untreated cats following 48 hours of ischemia were not significantly different. Despite the finding that the beneficial effects of mannitol were relatively short-lived (6 to 12 hours), the delay in the development of irreversible changes probably is important as it would allow a longer period of time for the institution of a more definitive form of therapy.
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D003907:Dexamethasone / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use*
D008353:Mannitol; D003907:Dexamethasone