Glucose-Insulin-Potassium Revived

The oxidative metabolism of the human heart was first defined by Bing and colleagues1 in a series of articles in the 1950s. Carbohydrates made up a relatively small part of the oxidative metabolism of the resting human heart. Focus on free fatty acids (FFAs) as a major myocardial fuel started with the finding in 1961 that FFAs inhibited glucose oxidation in the isolated heart.2 The next year, Sodi-Pallares et al3 wrote their seminal article that stirred interest in the possible therapeutic benefit of the promotion of glucose metabolism by administration of glucose-insulin-potassium (GIK). These basic concepts are still being explored today, 50 years later. This article covers the historical buildup of studies and ideas (the Table), the concept of a glucose–fatty acid interaction in health and disease, and the evolution of GIK and its application in beneficially altering the metabolic patterns in early-phase myocardial ischemia (Figure 1) and in the energy-depleted heart.View this table:Table. Evolution of Major Studies1–17 Leading to Present Concepts of Benefits of Glucose-Insulin-Potassium or Components ThereofFigure 1. The metabolic vicious circle in acute coronary syndrome (ACS). In early-phase ACS, we hypothesize a metabolic vicious circle in which pain, distress, and dyspnea provoke increased sympathetic drive, which in turn increases myocardial ischemic damage via tachycardia and indirectly by increasing plasma free fatty acids (FFAs). The latter event increases ischemic damage both by lipid loading in the ischemic tissue (fatty acyl Co A in Figure 2) and indirectly by blocking protective glycolysis.Although there have been many clinical studies on GIK given to patients with acute myocardial infarction (AMI) with variable results, few have focused on 2 crucial aspects of the clinical and experimental data: timing and metabolism (the Table). In the original article by Sodi-Pallares et …