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Diabetes and hyperglycemia impair activation of mitochondrial K(ATP) channels. Am J Physiol Heart Circ Physiol 2001 Apr;280(4):H1744-50

Date

03/15/2001

Pubmed ID

11247788

DOI

10.1152/ajpheart.2001.280.4.H1744

Abstract

Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (K(ATP)) channels. Acutely instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of the area at risk (AAR) for infarction in control, diabetic (3 wk after streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs, respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10 +/- 1% of AAR, P < 0.05) but did not produce protection in the presence of diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl; 23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3, 15 +/- 3 (P < 0.05), and 11 +/- 2% (P < 0.05), respectively]. There were no differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by radioactive microspheres) between groups. The results indicate that diabetes or hyperglycemia impairs activation of mitochondrial K(ATP) channels.

Author List

Kersten JR, Montgomery MW, Ghassemi T, Gross ER, Toller WG, Pagel PS, Warltier DC

Author

Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Blood Glucose
Blood Pressure
Carbon Dioxide
Coronary Circulation
Coronary Vessels
Diabetes Mellitus, Experimental
Diazoxide
Dogs
Endocardium
Heart Rate
Hemodynamics
Humans
Hyperglycemia
Membrane Proteins
Mitochondria
Myocardial Infarction
Oxygen
Potassium Channels
Vasodilator Agents
Ventricular Function, Left
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3