Energy metabolism of working muscles in patients after burn injury

Central to the process of optimizing burn care and rehabilitation is a
comprehensive understanding of the pathophysiological response. There is
evidence that impaired mitochondrial energy metabolism may play a major role in
the pathophysiology and impaired muscle function documented in patients
following major burn injury. Advanced research is required to further elucidate
the role of skeletal muscle mitochondrial dysfunction in the pathophysiological
response, particularly given the fact that mitochondria are sensitive to
environmental and pharmacological interventions.

Examine in vivo muscle energy metabolism in patients with burns, during rest,
(prolonged) exercise and recovery.

Observational case control study

not applicable

Patients will be asked to participate in two study sessions, with time between
both sessions of 1-3 weeks.

• session I (site: Martini Hospital) scheduled in combination with a routine
follow-up appointment at the Burn Centre of the Martini Hospital in Groningen.

In order to set the desired exercise workload of maximal individual rate of fat
oxidation (FATMAX; typically ~40% VO2max) in session II, aerobic exercise
capacity (VO2max) needs to be determined. In session 1 therefore, VO2max is
assessed using a standard maximal cardiopulmonary exercise test (CPET; bicycle
ergometry with respiratory gas analysis). Furthermore, body composition (body
height, body weight, waist circumference), maximal isokinetic leg muscle
strength (using a Cybex isokinetic dynamometer) and grip force (using the Citec
hand-held dynamometer) will be assessed.

The assessments are safe and non-invasive and will take approximately 2 hours.
Standard maximal cardiopulmonary exercise testing and isokinetic maximal
strength assessment have been previously used in patients with major burns
without adverse effects (St-Pierre, Choiniere et al. 1998, de Lateur,
Magyar-Russell et al. 2007). Patients will be asked to abstain from heavy
meals, caffeine and alcohol 2 hours prior to the test. After the assessments,
patients will receive two short questionnaires about habitual physical activity
and fatigue. These questionnaires can be filled in at home at any desired time
between the two assessment sessions. This will take approximately 15 minutes.

• session II (site: Neuroimaging Magnetic Resonance Center, University Medical
Center Groningen (UMCG)).

Working muscle metabolism: To determine energy and proton balance in the
muscle during exercise and the kinetics of metabolic recovery following
exercise, serial in vivo 31P MR spectra will be recorded non-invasively from
the m. vastus lateralis of the right leg. To this end, patients will be asked
to perform a 35 min upright bicycling exercise at FATMAX outside the MR scanner
(exercise bout 1) followed by a 10 min supine bicycling exercise at FATMAX
inside the MR scanner (exercise bout 2).
Application of 31P MRS in burn patients enables the non-invasive investigation
of the impact of burn injury on the bioenergetics of working muscles in vivo.
No adverse effects are expected. This and like protocols for in-magnet cycling
has previously been included and approved in clinical investigations of
metabolic myopathy patients protocols: 12-211/K (VLCAD; UMC Utrecht);
NL41313.042.12 (MCAD; UMCG); METC 2014.492 (Acute Nutritional Ketosis in VLCAD;
UMCG). The measurements in session II, including 31P MRS data collection, will
take approximately 2 hours.