title: The effects of early insulin treatment combined with thrombolysis in rat embolic stroke.
abstract: The therapeutic effect of insulin alone or insulin combined with 30 min delayed thrombolytic therapy was investigated in rats embolized in the right hemisphere with a fibrin clot made from autologous blood. Animals were killed seven days after embolization and the infarct volumes were measured in % of the affected hemisphere. Mortality was calculated as the number of animals dying spontaneously before the scheduled euthanasia. The median infarct volume in control animals (n = 12) was 24%. Insulin (3 IU kg(-1)) was given subcutaneously 15 min, 3 h, and 24 h after embolization (n = 12) and reduced median infarct volume to 11%. Human recombinant tissue plasminogen activator, 8 mg kg(-1), was infused intravenously during 45 min starting 30 min after embolization (n = 14), and the median infarct volume was 18% in this group. When the two treatments were combined, the median infarct volume was reduced to 11% (n = 14). The infarct volumes in the treatment groups were not significantly different from controls (p = 0.62, Kruskal Wallis test). Mortality rates increased from 0% among controls to 47% (p = 0.01) in the insulin alone and 38% (p = 0.02) in the combination therapy group. In conclusion, insulin treatment aiming at blood glucose levels around 2-4 mmol l(-1) was detrimental to clinical outcome causing significantly increased mortality.
authors.affiliation: Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. pm05@bbh.hosp.dk
authors.forename: Per
authors.initials: P
authors.lastname: Meden
authors.forename: Martin
authors.initials: M
authors.lastname: Andersen
authors.forename: Karsten
authors.initials: K
authors.lastname: Overgaard
authors.forename: Rune Skovgaard
authors.initials: RS
authors.lastname: Rasmussen
authors.forename: Gudrun
authors.initials: G
authors.lastname: Boysen
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002544:Cerebral Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D005343:Fibrinolytic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator