Alterations of myocardial amino acid metabolism in chronic ischemic heart disease.

Arteriovenous differences (A-V) of all naturally occurring amino acids, lactate, and oxygen were measured simultaneously with coronary sinus blood flow (CSBF) in 8 normal subjects and 11 patients with coronary artery disease at rest and during pacing stress. Mean values for CSBF and myocardial oxygen consumptions (MVO2) for the two groups were similar at rest and during pacing, although mean CSBF and MVO2 increased significantly in both groups in the paced as compared to the rest state. Alanine (ala) was the only amino acid released by the myocardium, while only glutamic acid(glu) demonstrated uptake. Mean A-V ala was negative at rest in the control and coronary disease groups (-4.8+/-3.8 vs. -22.0+/-3.0 nmol/ml, respectively), but was significantly more negative in the coronary group (P less than 0.001) and not statistically different than zero in the normals. A-V ala became significantly negative with pacing in the normals (-10.0+/-4.3 nmol/ml), remained unchanged in the coronary group (-23.0+/-2.9 nmol/ml), and was significantly more negative in the coronary group (P less than 0.05). Calculation of data on the basis of net ala flux ([A-V] X [CSBF X hematocrit]) yielded similar results as that obtained with A-V differences. A-V glu was significantly positive in normals (27.7 +/- 8.9 nmol/ml, P less than 0.01) and coronary patients (59.9 +/- 8.9 nmol/ml, P less than 0.01) at rest but significantly greater in the latter group (P less than 0.001). With pacing, A-V glu remained significantly greater than zero in coronary patients (35.3 +/- 6.3 nmol/ml) and decreased to zero in the normals (4.3 +/- 11.8 nmol/ml). Calculation of net glu flux (nmol/min) at rest yielded data similar to that based on A-V difference. With pacing, net glu flux in the coronary patients did not decrease due to the augmentation of CSBF. No relation between A-V glu or ala and CSBF, MVO2 or A-V lactate was noted. The data demonstrate that specific alterations of myocardial amino acid metabolism characterize patients with chronic ischemic heart disease.

[1]  P. Felig.  The glucose-alanine cycle. , 1973, Metabolism: clinical and experimental.

[2]  P. W. Hochachka,et al.  Purification and properties of dolphin muscle aspartate and alanine transaminases and thier possible roles in the energy metabolism of diving mammals. , 1974, The Biochemical journal.

[3]  P. W. Hochachka,et al.  Multiple end products of anaerobiosis in diving vertebrates. , 1975, Comparative biochemistry and physiology. B, Comparative biochemistry.

[4]  H. Swan,et al.  Measurement of Coronary Sinus Blood Flow by Continuous Thermodilution in Man , 1971, Circulation.

[5]  H. Horn,et al.  Quantitative bestimmung von L(+)-Milchsäure mit Milchsäuredehydrogenase , 1956 .

[6]  D. Williamson,et al.  Concentrations of free glucogenic amino acids in livers of rats subjected to various metabolic stresses. , 1967, The Biochemical journal.

[7]  L. Opie,et al.  Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats. , 1971, The Biochemical journal.

[8]  C. G. Webb,et al.  Evidence for the Release of Individual Amino-acids from the Resting Human Forearm , 1965, Nature.

[9]  J. Brosnan,et al.  Effects of ischaemia on metabolite concentrations in rat liver. , 1970, The Biochemical journal.

[10]  B. Safer.  The Metabolic Significance of the Malate-Aspartate Cycle in Heart. , 1975, Circulation research.

[11]  J. Tobin,et al.  Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels. , 1969, The Journal of clinical investigation.

[12]  J R Neely,et al.  Effect of Coronary Blood Flow on Glycolytic Flux and Intracellular pH in Isolated Rat Hearts , 1975, Circulation research.

[13]  J. L. Lilienthal,et al.  A rapid spectrophotometric method for determining oxygen content of dog's blood. , 1955, Journal of applied physiology.

[14]  L. Opie.  Substrate utilization and glycolysis in the heart. , 1971, Cardiology.

[15]  A. Svanborg,et al.  Myocardial metabolism of glucose, lactic acid, amino acids and fatty acids in healthy human individuals at rest and at different work loads. , 1961, Verhandlungen der Deutschen Gesellschaft fur Kreislaufforschung.

[16]  M. Rovetto,et al.  Mechanisms of Glycolytic Inhibition in Ischemic Rat Hearts , 1975, Circulation research.

[17]  T. Pozefsky,et al.  Effects of intrabrachial arterial infusion of pyruvate on forearm tissue metabolism. Interrelationships between pyruvate, lactate, and alanine. , 1972, The Journal of clinical investigation.

[18]  P. Felig,et al.  Alanine: Key Role in Gluconeogenesis , 1970, Science.

[19]  P. Felig,et al.  Fuel homeostasis in exercise. , 1975, The New England journal of medicine.

[20]  J. Williamson.  Glycolytic control mechanisms. II. Kinetics of intermediate changes during the aerobic-anoxic transition in perfused rat heart. , 1966, The Journal of biological chemistry.

[21]  S. Moore,et al.  The free amino acids of human blood plasma. , 1954, The Journal of biological chemistry.

[22]  George W. Snedecor,et al.  Statistical methods applied to experiments in agriculture and biology. , 1946 .

[23]  D. Edington,et al.  Energy metabolism of working muscle: concentration profiles of selected metabolites. , 1973, The American journal of physiology.

[24]  J R Neely,et al.  The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart. , 1972, The Biochemical journal.

[25]  E. Marliss,et al.  Muscle and splanchnic glutmine and glutamate metabolism in postabsorptive andstarved man. , 1971, The Journal of clinical investigation.

[26]  L. Opie.  The glucose hypothesis: Relation to acute myocardial ischaemia , 1970 .

[27]  P. Felig,et al.  Amino acid metabolism in exercising man. , 1971, The Journal of clinical investigation.

[28]  L. Opie,et al.  Comparison between metabolic changes in local venous and coronary sinus blood after acute experimental coronary arterial occlusion. , 1970, The American journal of cardiology.

[29]  L. Opie,et al.  The Value of Lactate and Pyruvate Measurements in the Assessment of the Redox State of Free Nicotinamide‐Adenine Dinucleotide in the Cytoplasm of Perfused Rat Heart , 1971, European journal of clinical investigation.

[30]  J. V. Benson,et al.  Accelerated chromatographic analysis of amino acids commonly found in physiological fluids on a spherical resin of specific design. , 1965, Analytical biochemistry.