Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.
The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.
Young
L H
LH
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
McNulty
P H
PH
Morgan
C
C
Deckelbaum
L I
LI
Zaret
B L
BL
Barrett
E J
EJ
D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D003327:Coronary Disease / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000032:analysis; D006321:Heart / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011506:Proteins / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D007773:Lactates; D011506:Proteins; D019344:Lactic Acid; D005947:Glucose