Anabolic resistance in critically ill patients

Abstract

Most patients who are critically ill lose muscle as a result of an inability to maintain rates of protein synthesis above those of protein breakdown. In addition to the effects of a procatabolic hormonal and cytokine milieu, which accelerate protein breakdown, age and immobility also influence the ability of muscle to maintain itself. Although the basal rates of protein turnover are not altered with aging, age is associated with a smaller ability to capture blood-borne amino acids as protein, the results of a decreased capacity for protein synthesis (total RNA/DNA) and decreased sensitivity and capacity of signaling proteins to indicate the availability of amino acids. Furthermore, muscle of older individuals is resistant to the effects of insulin in decreasing muscle proteolysis. Both of these effects are part of "anabolic resistance"-the inability of muscle to maintain its protein mass by appropriate stimulation of muscle protein turnover and inhibition of protein breakdown. Overlain on the effects of age are the effects of immobility, which has some of the characteristics of anabolic resistance. Immobility per se causes a decrease in muscle protein synthesis with no apparent stimulation of muscle protein breakdown; furthermore, muscle of immobilized legs is unable to stimulate muscle protein synthesis to the same extent as that of nonimmobilized legs when amino acids are infused, even at high rates.