Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality.
Recent evidence indicates that hyperglycemia is an important risk factor for the development of cardiovascular disease. We tested the hypothesis that myocardial infarct size is related to blood glucose concentration in the presence or absence of ischemic preconditioning (PC) stimuli in canine models of diabetes mellitus and acute hyperglycemia. Barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3-h reperfusion. Infarct size was 24 +/- 2% of the area at risk (AAR) for infarction in control dogs. PC significantly (P < 0.05) decreased the extent of infarction in normal (8 +/- 2% of AAR), but not diabetic (22 +/- 4% of AAR), dogs. Infarct size was linearly related to blood glucose concentration during acute hyperglycemia (r = 0.96; P < 0.001) and during diabetes (r = 0.74; P < 0.002) in the presence or absence of PC stimuli. Increases in serum osmolality caused by administration of raffinose (300 g) did not increase infarct size (11 +/- 3% of AAR) or interfere with the ability of PC to protect against infarction (2 +/- 1% of AAR). The results indicate that hyperglycemia is a major determinant of the extent of myocardial infarction in the dog.
Kersten
J R
JR
Division of Cardiovascular Diseases, Department of Anesthesiology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA. jkersten@mcw.edu
Toller
W G
WG
Gross
E R
ER
Pagel
P S
PS
Warltier
D C
DC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004285:Dogs; D006339:Heart Rate / Q000502:physiology; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D019194:Ischemic Preconditioning; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism*; D009994:Osmolar Concentration; D011887:Raffinose / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D011887:Raffinose