Using Arteriovenous Differences to Define Organ Balances

Just as the N balance technique can be applied across the whole body, so can the balance technique be applied across a whole organ or tissue bed. These measurements are made from the blood delivered to the tissue and from the blood emerging from the tissue via catheters placed in an artery to define arterial blood levels and the vein draining the tissue to measure venous blood levels. The latter catheter makes the procedure particularly invasive when applied to organs such as gut, liver, kidney, or brain (49, 50, 51 and 52). Less invasive are measures of muscle metabolism inferred from measurement of arteriovenous (A-V) differences across the leg or arm (51). Measurements have even been made across fat depots (53). However, the A-V difference provides no information about the mechanism in the tissue that causes the uptake or release that is observed. More information is gleaned from measurement of amino acids that are not metabolized within the tissue, such as the release of essential amino acids tyrosine or lysine, which are not metabolized by muscle. Their A-V differences across muscle should reflect the difference between net amino acid uptake for muscle protein synthesis and release from muscle protein breakdown. 3-Methylhistidine, an amino acid produced by posttrans-lational methylation of selected histidine residues in myofibrillar protein, which cannot be reused for protein synthesis when it is released from myofibrillar protein breakdown, is quantitatively released from muscle tissue when myofibrillar protein is degraded ( 32, 54). Its A-V difference can be used as a specific marker of myofibrillar protein breakdown (55, 56 and 57).

The limited data set of simple balance values across an organ bed is greatly enhanced when a tracer is administered and its balance is also measured across an organ bed. This approach allows a complete solution of the various pathways operating in the tissue for each amino acid tracer used. In some cases the measurement of tracer can become very complicated, requiring measurement of multiple metabolites to provide a true metabolite balance across the organ bed ( 58). Another approach using a tracer of a nonmetabolized essential amino acid has been described by Barrett et al. ( 59). This method requires a limited set of measurements with simplified equations to define specifically rates of protein synthesis and breakdown in muscle tissue. The conceptual simplicity of this approach with a limited set of measurements required makes it extremely useful for defining muscle-specific changes in response to a variety of perturbations (e.g., local infusion of insulin into the same muscle bed [60]). This approach has been expanded by others (61, 62 and 63).

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