Acute hyperglycemia abolishes ischemic preconditioning in vivo

Abstract

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.

Ischaemic preconditioning does not protect the heart in obese and lean animal models of Type 2 diabetes

“…However, in Type 1 diabetic animals the presence of a functional inducible nitric oxide synthase gene (producing high levels of nitric oxide) seems to aggravate ischaemic damage [21]. Hyperglycaemia is considered a major determinant of the extent of myocardial infarction in experimentally induced Type 1 diabetes and even in the absence of diabetes [22,23]. Our data demonstrate that hyperglycaemia in itself at the time of ischaemia-reperfusion is not responsible for abolishing the effects of IPC in Type 2 diabetes.…”

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

“…Some studies showed that hyperglycemia can increase myocardial IS and myocyte apoptosis, exaggerate LV failure, and decrease survival after MI/R by increasing inflammation and oxidative stress and abolishes ischemic preconditioning (4,13,14,20). In contrast, other studies demonstrated that hyperglycemia protected against ischemiainduced myocardial damage, decreased the myocardial IS and the number of apoptotic myocytes, and improved the recovery of heart function after MI/R (3,24).…”

Admission Hyperglycemia Is an Independent Predictor of Acute Kidney Injury in Patients With Acute Myocardial Infarction

“…32 We have previously reported that admission hyperglycemia abolishes ischemic preconditioning. 33, 34 It may also attenuate renoprotective effects of ischemic preconditioning in patients with AMI.…”