Cardioprotection by glucose-insulin-potassium: dependence on KATP channel opening and blood glucose concentration before ischemia.

Abstract

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K(+) (K(ATP)) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml x kg(-1) x h(-1)) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of K(ATP) channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 +/- 2% of the area at risk in control experiments. GIK decreased (P < 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 +/- 2 and 12 +/- 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 +/- 4%), hyperglycemia before ischemia (27 +/- 4%), or diabetes (25 +/- 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 +/- 3, 27 +/- 2, and 35 +/- 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by K(ATP) channel activation. However, glucose decreases K(ATP) channel activity, and this effect predominates when hyperglycemia is present before ischemia.

• Authors: John F LaDisa Jr, John G Krolikowski, Paul S Pagel, David C Warltier, Judy R Kersten
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 287 Issue 2 Pg. H601-7 (Aug 2004) ISSN: 0363-6135 [Print] United States
• PMID: 15044191 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Cardiotonic Agents
• Hypoglycemic Agents
• Insulin
• Potassium Channels
• glucose-insulin-potassium cardioplegic solution
• Adenosine Triphosphate
• Glucose
• Potassium
• Glyburide

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blood Glucose (metabolism)
• Cardiotonic Agents (administration & dosage)
• Diabetes Mellitus, Experimental (complications)
• Dogs
• Drug Administration Schedule
• Glucose (administration & dosage)
• Glyburide (pharmacology)
• Hemodynamics (drug effects)
• Hypoglycemic Agents (pharmacology)
• Insulin (administration & dosage, blood)
• Myocardial Infarction (etiology, pathology, prevention & control)
• Myocardial Ischemia (complications, physiopathology)
• Osmolar Concentration
• Potassium (administration & dosage)
• Potassium Channels (metabolism)