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Ann Thorac Surg 1997;63:1634
© 1997 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery (MC 958), University of Illinois at Chicago, Suite 417, 840 S Wood St, Chicago, IL 60612-7238
This article by Kjellman and associates adds further support to the beneficial effects of metabolic additives in blood cardioplegic solutions. In contrast to most previous studies, which used amino acid precursors of Krebs cycle intermediates (ie, aspartate and glutamate), Kjellman and associates gave the Krebs cycle intermediate (
-ketoglutarate) directly, and found similar results. Their use of only 30°C instead of 37°C during warm cardioplegic administration may, however, have reduced the metabolic effects. This article also highlights the problem many investigators in this field have encountered. Although the beneficial effects of amino acid enrichment in the precise experimental setting have been documented repeatedly in damaged hearts, it has been difficult to show improvement in patients. This is because the amount of preexisting myocardial disease and operative procedure are quite variable, making it much more difficult to compare postoperative results. In addition, the parameters that can be measured in the clinical setting are relatively insensitive compared with those used in the experimental laboratory. Therefore, only by using large numbers of patients, with depressed cardiac function, have investigators been able to demonstrate the benefits of amino acids supplementation.
In this study, although the hemodynamic function is not dramatically altered in low-risk patients, there is substantial improvement in biochemical parameters. These include improved oxygen uptake and subsequent quicker return to oxidative metabolism after unclamping, and lower creatine kinase-MB and troponin T release. This indicates a marked improvement in myocardial cellular preservation, and supports the use of amino acids in elective patients, because this improvement in protection may become critical if an untoward event should occur. To emphasize the benefits of amino acid enrichment of cardioplegic solutions in elective operations, my colleagues and I have shown, for example, augmented myocardial oxygen and glucose uptake in patients with chronic congestive heart failure, ventricular hypertrophy, or hypertension. The mechanism of action of amino acids enrichment, however, remains uncertain, as Kjellman and associates did not demonstrate an increase in amino acid uptake in the present study, and recent studies in our laboratory using hypoxic neonatal hearts show improved hemodynamic function without enhanced oxygen uptake during amino acid delivery.
We use glutamate rather than -ketoglutarate because glutamate may offer several advantages. Glutamate has been shown to be safe in thousands of patients and has myocardial metabolic effects documented recently by Svedjeholm and associates. Glutamate is also important in regulating the nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide (reduced form) balance in cytosol of cells, and thereby enhances glycolysis during ischemia. Glutamate improves clearance of lactate and NH3 by reactions involving transamination of pyruvate to alanine, and glutamate to glutamine. It contributes to the alternative anaerobic pathway for generation of high-energy phosphates by substrate-level phosphorylation in the Krebs cycle, but this is less active during cold ischemia. Finally, when given warm, glutamate replenishes Krebs cycle intermediates by its conversions to -ketoglutarate. We use both glutamate and aspartate as the combination has been shown to further enhance metabolic recovery in experimental and clinical studies. We deliver these amino acids only during warm induction and reperfusion as this is when they are metabolically most active. Because glutamate is also a neurotransmitter, there has been some concern it may be detrimental during periods of low flow. This is extremely unlikely because (1) glutamate levels in the brain are more than 100 times higher than in serum, (2) the cardioplegic administration raises serum levels only two to three times, which is an insignificant increase with respect to the brain, and (3) glutamate does not cross the blood-brain barrier. Whether aspartate and glutamate are the preferred amino acids remains to be defined, but hopefully with data such as those presented by Kjellman and associates, the use of amino acids enrichment will become more routine in surgical procedures.
Related Article
-Ketoglutarate to Blood Cardioplegia Improves Cardioprotection
Ann. Thorac. Surg. 1997 63: 1625-1633.
This article has been cited by other articles:
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  M. T. Kronon, B. S. Allen, K. S. Bolling, S. Rahman, T. Wang, H. S. Maniar, S. M. Prasad, and M. N. Ilbawi The role of cardioplegia induction temperature and amino acid enrichment in neonatal myocardial protection Ann. Thorac. Surg., September 1, 2000; 70(3): 756 - 764. [Abstract] [Full Text] [PDF]
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