Patients with chronic HF (
heart failure) experience
muscle atrophy during the course of the disease. The mechanisms underlying
muscle atrophy in HF, however, are not understood. Thus we evaluated leg
phenylalanine balance and kinetics in HF patients and controls following a brief fast (24 h) and under euglycaemic-hyperinsulinaemic-hyperaminoacidaemic conditions to determine whether HF increases
muscle protein catabolism in response to nutritional deprivation and/or diminishes the anabolic response to meal-related stimuli (
insulin and
amino acids) and whether alterations in
protein metabolism correlate to circulating
cytokine levels. No differences in
phenylalanine balance, rate of appearance or rate of disappearance were found between patients and controls under fasting conditions. However, the anabolic response to hyperinsulinaemia-hyperaminoacidaemia was reduced by more than 50% in patients compared with controls. The diminished anabolic response was due to reduced suppression of the leg
phenylalanine appearance rate, an index of
protein breakdown, in HF patients; whereas no group difference was found in the increase in the leg
phenylalanine disappearance rate, an index of
protein synthesis. The diminished responses of both
phenylalanine balance and appearance rate to hyperinsulinaemia-hyperaminoacidaemia were related to greater circulating
IL-6 (interleukin-6) levels. Our results suggest that, following a brief period of nutritional deprivation, HF patients demonstrate an impaired
muscle protein anabolic response to meal-related stimuli, due to an inability to suppress muscle proteolysis, and that this diminished
protein anabolic response correlates with markers of immune activation. The inability to stimulate
muscle protein anabolism following periods of
nutritional deficiency may contribute to muscle wasting in HF patients.