Diabetes abolishes ischemic preconditioning: role of glucose, insulin, andosmolality

Recent evidence indicates that hyperglycemia is an important risk factor fo r the development of cardiovascular disease. We tested the hypothesis that myocardial infarct size is related to blood glucose concentration in the pr esence or absence of ischemic preconditioning (PC) stimuli in canine models of diabetes mellitus and acute hyperglycemia. Barbiturate-anesthetized dog s were subjected to a 60-min period of coronary artery occlusion and 3-h re perfusion. Infarct size was 24 +/- 2% of the area at risk (AAR) for infarct ion in control dogs. PC significantly (P < 0.05) decreased the extent of in farction in normal(8 +/- 2% of AAR), but not diabetic (22 +/- 4% of AAR), d ogs. Infarct size was linearly related to blood glucose concentration durin g 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 osm olality caused by administration of raffinose (300 g) did not increase infa rct size (11 +/- 3% of AAR) or interfere with the ability of PC to protect against infarction (2 +/- 1% of AAR). The results indicate that hyperglycem ia is a major determinant of the extent of myocardial infarction in the dog .