Cardioprotection by glucose-insulin-potassium: dependence on K_ATPchannel 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.

Hyperglycemia during acute myocardial infarction in patients who are treated by primary percutaneous coronary intervention: Impact on long-term prognosis

“…NDNH, non-diabetics/ non-hyperglycemic; NDH, non-diabetics/hyperglycemic. to fatal arrhythmias [17], impaired microvascular function with no-reflow phenomenon [18] and the decrease activity of K-ATP channels [19]. Hyperglycemia has a pathogenic role in thrombosis, thrombophilia and platelet aggregation [20] There is a large body of evidence suggesting association between myocardial infarction and inflammation.…”

Effect of glucose–insulin–potassium on hyperlactataemia in patients undergoing valvular heart surgery

“…Another plausible explanation would be that although hyperglycaemia is considered to abolish the beneficial effect of GIK, 34 there was a theory that increased osmolarity of the extracellular space caused by hyperglycaemia with GIK infusion could reduce cellular oedema during ischaemia. 24,35 Indeed, hyperglycaemia frequently developed in the GIK group even in a study reporting positive results.…”

Perioperative Organ Protection in Cardiac Surgery

“…It was also observed an improvement in ventricular contractility after ischemic episodes with morphine and fentanyl (28). Besides participating in the triggering of the cascade of ischemic preconditioning, opioids also seem to mediate the memory phase in some animal species and the opioid-induced cardioprotection appears to be modulated by the activation of cardiac receptors, independent of the action of these drugs on the central nervous system [40][41] . It has been proposed that opioid-induced cardioprotection is processed by the activation of ATP-dependent potassium channels, possibly in the mitochondrial membrane (29).…”

“…Regarding the 2 receptor agonists, clonidine seems to be less effective than high thoracic epidural anesthesia in reducing perioperative stress and troponin release in patients undergoing CABG (40). Additionally, experimental and small clinical trials showed encouraging results for the improvement of myocardial performance in patients undergoing cardiac surgery with the infusion of a solution containing glucose, insulin and potassium (GIK) (41). The mechanism by which GIK solution promotes cardioprotection seems to be related to the restoration of the activity of the ATP-dependent potassium channels by insulin, since glucose decreases the activity of this channel and insulin infusion can decrease apoptosis induced by ischemia and reperfusion (42).…”