The effects of early insulin treatment combined with thrombolysis in rat embolic stroke

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.