Acute hyperglycemia abolishes ischemic preconditioning in vivo.
Ischemic preconditioning provides a powerful means to reduce myocardial infarct size in vivo and has been proposed to limit the extent of myocardial infarction in patients. In contrast, hyperglycemia correlates with increases in mortality after acute myocardial infarction. Thus we hypothesized that acute hyperglycemia alters the protection afforded by ischemic preconditioning, and this hypothesis was tested in acutely instrumented dogs subjected to a prolonged (60 min) coronary artery occlusion and 3 h of reperfusion. Ischemic preconditioning was elicited by four 5-min occlusion-reperfusion periods in the presence or absence of an intravenous infusion of 15% dextrose in water to produce acute hyperglycemia (plasma glucose concentration of 300 mg/dl). The dose-dependent effects of hyperglycemia on myocardial infarct size independent of preconditioning stimuli were further evaluated in dogs subjected to increases in plasma glucose concentrations to either 300 or 600 mg/dl. Infarct size (triphenyltetrazolium staining) was 24 +/- 2% of the area at risk in control dogs and was significantly (P < 0.05) decreased by ischemic preconditioning (8 +/- 1%). Modest degrees of hyperglycemia (300 mg/dl) had no effect on infarct size (34 +/- 4%) but abolished the protective effect of ischemic preconditioning (30 +/- 5%). In contrast, profound hyperglycemia (600 mg/dl) increased infarct size (44 +/- 6%). Hemodynamics and coronary collateral blood flow (radioactive microspheres) were similar between groups. Thus acute hyperglycemia adversely modulates myocardial injury in response to ischemia in vivo.
Kersten
J R
JR
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Schmeling
T J
TJ
Orth
K G
KG
Pagel
P S
PS
Warltier
D C
DC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D005947:Glucose / Q000008:administration & dosage; D006339:Heart Rate; D006439:Hemodynamics; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D019194:Ischemic Preconditioning; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011188:Potassium / Q000097:blood; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose; D011188:Potassium