Skeletal muscle and whole body protein turnover in cardiac cachexia: influence of branched‐chain amino acid administration

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Abstract
Muscle protein wasting commonly accompanies severe heart failure. The mechanism of this socalled cardiac cachexia has been investigated in eight patients with an average body weight decrement of 19%, whose results have been compared with those from 11 healthy control subjects. Exchanges of tyrosine and 3-methylhistidine across leg tissue were used as specific indicators of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using a stable isotope labelling technique with L-[1-13C] leucine as tracer. In patients with cardiac cachexia there were greater values, relative to those values in normal control subjects, of leg efflux of tyrosine (.sbd.8.1 .+-. 0.6 nmol 100 ml leg tissue-1 min-1 vs. .sbd.4.2 .+-. 0.3 nmol 100 ml-1 min-1 (P < 0.01)) and of 3-methylhistidine (-0.8 .+-. 0.1 nmol 100 ml leg tissue-1 min-1 vs. -0.1 .+-. 0.02 nmol 100 ml-1 min-1 (P < 0.005), mean .+-. SEM). The results suggest that in patients with cardiac cachexia the state of net negative protein balance across leg tissue is associated with an increased rate of myofibrillar protein breakdown. In cardiac cachexia, neither efflux of tyrosine (-8.4 .+-. 0.7 nmol 100 ml leg tissue-1 min-1) nor of 3-methylhistidine (-1.0 .+-. 0.2 nmol 100 ml leg tissue-1 min-1) were significantly altered by branched-chain amino acid (BCAA) infusion to plasma concentrations of 1300 .+-. 14 .mu.mol ml-1, i.e., four times normal plasma values (282 .+-. 11 .mu.mol ml-1). Similarly, in normal subjects, effluxes of tyrosine (-3.7 .+-. 0.5 nmol 100 ml-1 min-1) were unaltered by BCAA administration. Nevertheless, BCAA infusion caused a net retention of total amino and amide nitrogen in leg tissue of cachectic patients, but not in that of normal control subjects. The results suggest that BCAA have no acute effect on muscle protein synthesis or breakdown in normal subjects or in cardiac patients with muscle wasting, but may promote increases in the intracellular pool of amino acid nitrogen, which may have beneficial longer term effects. In cardiac cachexia, differences from normal in the components of the leucine plasma flux (determined by stable isotope labelling techniques) suggested that there was a depression in whole body leucine flux (protein breakdown), leucine oxidation and protein synthesis compared with normal [79 .+-. 24 .mu.mol kg-1 h-1 vs. 133 .+-. 27 .mu.mol kg-1 h-1 (P < 0.0001) (mean .+-. SD), 25 .+-. 20 vs. 40 .+-. 10 mol kg-1 h-1 (P < 0.0001), and 54 .+-. 7 vs. 89 .+-. 20 .mu.mol kg-1 h-1 (P < 0.0001), respectively]. These results suggest that although there is an overall depression of whole body protein turnover, in cardiac cachexia, this is associated with elevations of myofibrillar protein breakdown from skeletal muscle in the leg.