The mechanism of amino acid loading in improving postischemic myocardial recovery

During induced ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is altered. Following reperfusion, stunned myocardium uses oxygen and substrate inefficiently, leading to poor functional recovery. However, amino acids may be used as anaplerotic metabolic substrates during and after ischemia, utilizing transamination of amino acids to form high-energy phosphates via the tricarboxylic acid cycle. We investigated if loading hearts with a physiologic spectrum of amino acids prior to ischemia could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were loaded with a 0.05, 0.1, 0.5, 1, 2, or 5% amino acid perfusion prior to cardioplegic ischemia. Following reperfusion, functional recovery revealed that hearts perfused with 0.05 and 0.1% amino acids had improved contractility and compliance vs untreated controls. To determine if the mechanism of amino acid loading in improving postischemic function was enhancement of high-energy phosphate resynthesis, nucleotides and nucleosides were measured. While all preischemic values were equivalent, amino-acid-loaded hearts had significantly greater high energy nucleotides at end ischemia and after reperfusion. These data demonstrate that metabolism, as well as function, is improved with amino acid loading prior to ischemia, which allowed for better internal reparative work during ischemia and external contractile work after ischemia. This strategy may have application in cardiac surgery.