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.