Burn patients undergo metabolic changes that lead to decreased glucose metabolism and increased protein degradation leading to muscle wasting. While the Center investigators have previously documented whole-body metabolism using stable isotopes and other biochemical approaches, regional or organ-specific metabolic changes after burn injury have been more difficult to study. Recently, the investigators in Project 2 have developed, validated and applied new procedures for measuring blood flow, blood volume oxygenation utilization and glucose metabolism in a variety of tissues and protein synthesis/degradation in skeletal muscle. In addition, the investigators have developed micro PET (μPET) to perform some of these measurements at the bedside of critically ill patients.

Hypothesis Guiding the Research

PET technology can be used to quantify regional metabolism and measure important metabolic parameters to better understand their alterations after injury. It is proposed that there are specific energy requirements for peripheral skeletal muscle and kidney that are at or below normal levels and for the liver and heart, these requirements are two- to three-fold or more above normal. It is also proposed that glucose is taken up into skeletal muscle at or below normal rates and undergoes primarily anaerobic glycolysis to produce lactate, alanine, and little energy. Third, it is proposed that protein synthesis is at or below normal levels in peripheral skeletal muscle and can be modified by anabolic factors.

Specific Aims

Specific Aim 1 measures blood flow, oxygen utilization, fatty acid and glucose metabolism in skeletal and cardiac muscle, kidney and liver in burn patients. For patients who are unstable to be transported to the PET imaging suite, these measurements are restricted to bedside evaluations of the metabolic parameters in skeletal muscle using our μPET device.

Specific Aim 2 applies our methods for measuring muscle protein synthesis rate (PSR) and catabolism to metabolic studies in burn patients. For patients who are unstable to be transported to the PET imaging suite, these measurements are performed at the bedside using our μPET device.

Specific Aim 3 evaluates the utility of regional measurements of glucose metabolism, PSR and protein catabolism for monitoring the effects of therapeutic interventions in burn patients. Patients are treated with Oxandrolone (0.2 mg/kg/day. p.o.) or placebo and imaged with 18FDG or 11C Met. Imaging is performed before treatment and at 4-month intervals thereafter for up to one year.

Specific Aim 4 measures blood flow, oxygen utilization, and glucose and fatty acid metabolism in skeletal and cardiac muscle, kidney and liver by μPET as a function of time in model systems after thermal injury. To improve our understanding of the relationship between the PET measurements of glucose and fatty acid utilization and substrate oxidation, simultaneous steady-state kinetic studies of the metabolic fates of [U-13C]glucose and
[1-13C]palmitic acid are made in the human subjects and model systems.

Innovation

Very little direct and detailed information is known about the individual organ or tissue contributions to the well-characterized metabolic changes that occur post-injury. PET imaging is ideally suited to measuring these regional metabolic changes in humans and model systems. The adaptive use of μPET to bedside imaging of the extremities in patients who cannot be safely moved to a whole-body PET scanner is groundbreaking. The application of quantitative metabolic imaging provides both a better understanding of the metabolic changes that occur after severe burns and a rational means to test therapeutic interventions.

For more information about this project, please contact Dr. Alan Fischman.

[top]