Hyperglycemia prevents isoflurane-induced preconditioning against myocardial infarction

Abstract

Background: Volatile anesthetics stimulate but hyperglycemia attenuates activity of mitochondrial adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that acute hyperglycemia interferes with isoflurane-induced preconditioning in vivo. Methods: Barbiturate-anesthetized dogs (n = 79) were instrumented for measurement of hemodynamics. Myocardial infarct size and collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of normal saline (normoglycemic controls) or 15% dextrose in water to increase blood glucose concentrations to 300 or 600 mg/dl in the absence or presence of isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) in separate experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. Results: Myocardial infarct size was 26 ± 1% of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 ± 2 and 13 ± 1% during 0.5 and 1.0 MAC, respectively). Hyperglycemia alone did not alter infarct size (26 ± 2 and 33 ± 4% during 300 and 600 mg/dl, respectively). Moderate hyperglycemia blocked the protective effects of 0.5 MAC (25 ± 2%) but not 1.0 MAC isoflurane (13 ± 2%). In contrast, severe hyperglycemia prevented reductions of infarct size during both 0.5 MAC (29 ± 3%) and 1.0 MAC isoflurane (28 ± 4%). Conclusions: Acute hyperglycemia attenuates reductions in myocardial infarct size produced by isoflurane in dogs.