Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease.
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BACKGROUND: Experimental studies indicate that greater skeletal muscle protein breakdown is a trigger for the cachexia that often is prevalent in chronic obstructive pulmonary disease (COPD). OBJECTIVE: We compared myofibrillar protein breakdown (MPB) with whole-body (WB) protein breakdown (PB) in 9 cachectic COPD patients [x +/- SEM forced expiratory volume in 1 s (FEV(1)): 48 +/- 4% of predicted], 7 noncachectic COPD patients (FEV(1): 53 +/- 5% of predicted), and 7 age-matched healthy control subjects, who were matched by body mass index with the noncachectic patients. DESIGN: After the subjects fasted overnight (10 h) and discontinued the maintenance medication, a primed constant and continuous infusion protocol was used to infuse L-[ring-(2)H(5)]-phenylalanine and L-[ring-(2)H(2)]-tyrosine to measure WB protein turnover and L-[(2)H(3)]-3-methylhistidine to measure WB MPB. Three arterialized venous blood samples were taken between 80 and 90 min of infusion to measure amino acid concentrations and tracer enrichments. RESULTS: Body composition, WB protein turnover, and WB MPB did not differ significantly between the noncachectic COPD and control subjects. Cachectic COPD patients had lower fat mass and fat-free mass values (both: P < 0.01) than did the noncachectic COPD patients. WB MPB was significantly (P < 0.05) higher in the cachectic COPD group (18 +/- 3 nmol . kg(-1) . min(-1)) than in the combined control and noncachectic COPD groups (10 +/- 1 nmol . kg(-1) . min(-1)), but WB protein turnover did not differ significantly between the groups. Correlations with fat-free mass were significant (P < 0.05) for plasma glutamate and branched-chain amino acids, and that for WB MPB trended toward significance (P = 0.07). CONCLUSION: Cachexia in clinically stable patients with moderate COPD is characterized by increased WB MPB, which indicates that myofibrillar protein wasting is an important target for nutritional and pharmacologic modulation.
author list (cited authors)
Rutten, E., Franssen, F., Engelen, M., Wouters, E., Deutz, N., & Schols, A.
complete list of authors
Rutten, Erica PA||Franssen, Frits ME||Engelen, Marielle PKJ||Wouters, Emiel FM||Deutz, Nicolaas EP||Schols, Annemie MWJ