High-dose insulin in experimental myocardial infarction in rabbits: protection against effects of hyperglycaemia.
BACKGROUND
Hyperglycaemia at the time of acute myocardial infarction (AMI) is a predictor of survival and is associated with increased mortality and morbidity in patients with or without diabetes mellitus. On the other hand, insulin has been shown to reduce myocardial injury in experimental studies but its benefits have not been confirmed in clinical studies.


METHODS
The isolated perfused heart model was used to examine the direct effect of incremental doses of insulin and varying degrees of hyperglycaemia on infarct size and cardiomyocyte apoptosis in rabbit hearts. The rabbit hearts were subjected to 30-min ischaemia and 2.5-h reperfusion.


RESULTS
Insulin, given alone just before reperfusion, dramatically reduced infarct size in a dose-dependent manner (75-300 μU/ml) during experimental myocardial infarction (46%±2% to 10.9%±3%, P<.001). Acutely elevated glucose levels (33 mmol/L) induced a significantly greater infarct size and cardiomyocyte apoptosis compared to hearts subjected to normal glucose levels. On the other hand, high-dose insulin (300 μU/ml) given 5 min before reperfusion attenuated the extent of infarction and reduced apoptosis in hearts that were exposed to high glucose levels.


CONCLUSIONS
Acutely elevated levels of glucose induced larger infarct area during ischaemia-reperfusion, and this is mediated through proapoptotic pathways. Insulin, when given just before reperfusion, confers cardioprotection in a dose-dependent manner and reverses the detrimental effect of acute hyperglycaemia. High-dose insulin as well as maintaining normoglycaemia remain important factors that improve outcomes following myocardial infarction.
Wong
Vincent W
VW
Department of Cardiology, Royal North Shore Hospital, Sydney, NSW 2065, Australia.
Mardini
Mahidi
M
Cheung
N Wah
NW
Mihailidou
Anastasia S
AS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D011817:Rabbits
D001786:Blood Glucose; D007328:Insulin