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IV.   Anticatabolic Strategy
        (The Rationale for Anticatabolic Agents)

Anticatabolic therapy is aimed at attenuating the degree of protein loss after burn injury. A number of the agents considered to be anticatabolic also have direct anabolic activity.

The agents and methods to be described in this section are predominately anti-catabolic and in the next section predominantly anabolic.

The optimum provision of protein with high biologic value has been presented as has the potential anabolic action of the many bioactive peptides produced during protein hydrolysis. These potent peptides do not require energy to be absorbed and increase nitrogen retention in excess of the nitrogen intake reflecting anticatabolic and anabolic properties.

Glutamine is the most abundant amino acid in the human body constituting more than 60% of the total amino acid pool.^22,23 Glutamine is nonessential in the normal state, ie, it need not be obtained from the diet because it can be synthesized mainly in skeletal muscle from any of the other 19 amino acids in human protein, via the generation of a -ketoglutarate in the Krebs cycle. The a -Ketoglutarate can then be converted into glutamate and then glutamine, by successive additions of nitrogen groups. However, the rate of production cannot keep up with demands after burn injury, making it also an essential amino acid after severe injury or infection. Glutamine makes up less than 15% of the protein content in skeletal muscle but comprises over 30% of the amino acids exiting muscle. Muscle contains a large, labile glutamine pool that functions to maintain the body’s nitrogen balance. Key functions are described below.

Glutamine becomes an essential amino acid after severe injury due to the large efflux of glutamine from skeletal muscle for a variety of needs. In the first 2 to 3 days after injury, the large pool of free glutamine in skeletal muscle declines by more than 50%. Burn injury is known to rapidly lead to an increase in gut permeability, and glutamine administration has been suggested but not yet proven to protect the gut membrane.

The availability of glutamine is now recognized as a rate-limiting step in muscle protein synthesis and the rate of protein turnover in muscle depends in part on the availability of glutamine. The catabolism and loss of intramuscular free glutamine in surgical patients has been shown to be attenuated by providing isocaloric, isonitrogenous parenteral nutrition that includes supplemental glutamine (20 g/d).

Arginine is an amino acid recognized to be beneficial for wound healing and may be considered anticatabolic in the injured patient population when given in very large doses. No data on high dose arginine replacement therapy is available for burn patients.

There are two categories of anti-inflammatory agents which can have anticatabolic activity. These are antioxidants and anticytokines. Although pro-inflammatory cytokines initiate oxidant release and vice versa, we will discuss the categories separately.

Oxidant induced protein denaturation with subsequent breakdown, is a well recognized process after burn injury. A marked increase in oxidant release post burn and a well recognized decrease in anti-oxidant defenses, is also well defined. Antioxidant replacement is considered a standard of nutritional care. Although this approach is logical, there is no available data to indicate a preservation of lean mass occurs post burn with the use of added antioxidants.

The parts of the cell, i.e. cell membranes and cytosol, where various antioxidants protect against protein denaturation, are shown.

Pro-inflammatory cytokines, tumor necrosis factor TNF, interleukins 1,6 have been shown to be associated with proteolytic activity. The production of these factors is markedly increased after burn injury. Since these cytokines appear to be involved with post burn (trauma) catabolism, blockade or attenuation would appear to be of benefit. Although promising to date this approach has not been shown to be effective in burn patients in decreasing catabolism. However, current available agents will be described since more research in this area may show benefit.

Burn surgery is well recognized to produce an immense short term and long term psychological stress due both to pain and to anxiety. The psychological stress response is seen after any burn injury. Recent evidence would indicate that this stress generates a hypermetabolic catabolic state through the same neuro-pathway initiated by physical stress.

The nervous system, where all stressful stimuli exert their initial effects, is well documented to play a crucial role in the generation of adequate stress responses by correctly integrating endocrine and immune system functions to maintain homeostasis of the organism. The specific individual pattern of stress response is also determined by modulation of emotional influences. Emotional structures are located mainly in the limbic system. The hypothalamus, in particular, with its connections to both central and peripheral nervous structures, and neuroendocrine integrated systems is concerned with the organization of motivated behavioral and endocrine responses.

The neuroendocrine cascade following the application of emotional stress is generally similar to that determined by other physical stressors. In humans, mental stress is known to induce pronounced and reproducible activation of the sympathoadrenal system, with elevation of plasma epinephrine and norepinephrine concentrations and subsequent metabolic consequences, identical to the burn insult itself.