Glucose-Insulin-Potassium for Acute Myocardial Infarction

Abstract

T he "holy grail" in the field of cardioprotection is to develop pharmacological agents that can be administered as adjunctive treatment to reperfusion that will reduce myocardial infarct size and improve clinical outcomes. Numerous pharmacological agents and strategies have been studied over the years with variable results in both animal models and humans. Of drugs that have been studied, only a few have shown benefit in clinical trials. Aside from agents or devices than can restore and maintain reperfusion (thrombolytics, balloons, stents, aspirin, clopidogrel, IIb/IIIa inhibitors, lowmolecular-weight heparin, and others), the only commonly used adjunctive agents shown to have cardioprotective effects when administered early after coronary occlusion and in addition to reperfusion are ␤-blockers. Angiotensinconverting enzyme inhibitors and angiotensin receptor blockers are also used, but these can be given after infarction (as late as 1 week) and must be continued long-term to reduce left ventricular remodeling. Recently, adenosine and induced hypothermia have also shown promise as early adjunctive agents. For example, when intravenous adenosine was coupled with early reperfusion therapy, myocardial infarct size by single-photon emission computed tomography analysis and the composite end point of death and heart failure were reduced at 6 months. 1 Hypothermia, induced by use of a heat-exchange cooling catheter, benefited a subgroup of patients who were successfully cooled to Յ35°C before reperfusion. 2 Superoxide dismutase, magnesium, inhibitors of neutrophil adhesion, complement inhibitors, fluosol, RheothRx, the K ATP channel/nitrate nicorandil, and others failed to show a benefit as adjuncts to reperfusion. 3 Clinical research evaluating many of these agents in acute myocardial infarction has halted.One of the most controversial of these adjunctive agents still under investigation is GIK (glucose-insulin-potassium), 4,5 a "cocktail" delivered at the time of infarction that has demonstrated variable results in both the prereperfusion and postreperfusion eras. GIK was one of the first agents to be studied for protection of the ischemic myocardium. 6,7 Numerous reasons exist for the continued interest in GIK despite its variable track record in clinical trials: (1) Substantial laboratory evidence supports a cardioprotective effect in various models of ischemia/reperfusion; (2) some clinical trials have demonstrated positive results in specific patient subgroups; (3) the treatment is relatively "nontoxic" and free of major clinical side effects; and (4) recent evidence suggests that insulin itself, a component of GIK, administered as a strategy to restore normoglycemia, may be cardioprotective because it has antiinflammatory, antiapoptotic, and provasodilatory properties. In addition, the recognition that hyperglycemia is an important independent factor associated with a poor outcome in the setting of acute myocardial infarction 8 and other critical illnesses has renewed interest in the use of insulin. A byprodu...

Glucose-Insulin-Potassium Revived

“…Subsequently, in 1983, Apstein et al 13 showed that hyperglycemia and insulin increased glycolytic flux and prevented ischemic contracture in the acutely ischemic rabbit heart. In an influential meta-analysis, Kloner and Nesto 14 found that even delayed GIK reduced 30-day patient mortality by ≈18%. Stimulation of glucose oxidation in rodent hearts decreased infarct size.…”

Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

“…The debate on GIK has been described in detail in the past and has raged for decades. 68 The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care (IMMEDIATE) trial was recently published. 69 This large, randomized, placebo-controlled, doubleblind, multicenter trial tested the efficacy of administering a 12-hour infusion of GIK started in the out-of-hospital setting by paramedics in patients with high probability of acute coronary syndromes.…”

Wytyczne ESC dotyczące cukrzycy, stanu przedcukrzycowego i chorób układu sercowo- -naczyniowego opracowane we współpracy z EASD

“…Modulacja metabolizmu poprzez podawanie glukozy, insuliny i potasu (GIK), niezależnie od obecności cukrzycy i stężenia glukozy w osoczu, opiera się na założeniu, że zwiększenie stężenia potasu wewnątrzkomórkowego stabilizuje kardiomiocyty i ułatwia transport glukozy do komórek [324]. Do innych potencjalnych korzyści należą zmniejszenie beta-oksydacji wolnych kwasów tłuszczo-wych, lepsze wykorzystanie glukozy w procesie produkcji energii i poprawa czynności śródbłonka i efektów fibrynolizy [301].…”

“…Do innych potencjalnych korzyści należą zmniejszenie beta-oksydacji wolnych kwasów tłuszczo-wych, lepsze wykorzystanie glukozy w procesie produkcji energii i poprawa czynności śródbłonka i efektów fibrynolizy [301]. Jak wynika z pracy przeglądowej Kloner i Nesto [324], w badaniach RCT nie wykazano zmniejszenia śmiertelności ani chorobowości. Ten brak efektu może być spowodowany zwiększeniem stężenia glukozy w osoczu lub niekorzystnym wpływem obciążenia płynami spowodowanego wlewem GIK.…”