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

TY - JOUR

T1 - The effects of early insulin treatment combined with thrombolysis in rat embolic stroke.

AU - Meden, Per

AU - Andersen, Martin

AU - Overgaard, Karsten

AU - Rasmussen, Rune Skovgaard

AU - Boysen, Gudrun

N1 - Keywords: Animals; Blood Glucose; Carotid Arteries; Cerebral Infarction; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Hypoglycemic Agents; Insulin; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Time Factors; Tissue Plasminogen Activator

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12069290

SN - 0161-6412

VL - 24

SP - 399

EP - 404

JO - Neurological Research

JF - Neurological Research

IS - 4

ER -