Critical Illness, Pharmaconutrients, Protein Metabolism
Conditions
Keywords
critical illness, protein metabolism, pharmaconutrients
Brief summary
Introduction: Protein loss during critical illness is an important problem and is shown to predict overall survival. In animal studies, infusion of leucine is shown to increase the synthesis of muscle protein by 30-40% and decrease protein degradation by 30%. Objectives: Compared to saline, an amino acid or 3hydroxybutyrate infusion in the femoral artery will promote protein synthesis and inhibit breakdown assessed with local a/v phenylalanine and tyrosine tracer kinetics in healthy volunteers. These effects will include distinct alterations in muscle signal events, in particular mTOR. Methods: n = 10 healthy male subjects are equipped with catheters in aa. femorals and vv. femorals bilaterally under local anaesthetics. Each study comprises a 3-hour basal period and a 3-hour period with hyperinsulinaemic-euglycaemic clamp. During the test, samples of arterial and venous blood and 4 muscle biopsies are obtained. The intervention contain continues saline infusion compared to either amino acids (Vamin) or 3hydroxybutyrate solution FFa-3OHB. Perspectives: This study elucidates the direct effect of aminoacids and ketone bodies on muscle protein metabolism in humans and contribute to further development of nutritional therapy in human catabolic states.
Interventions
DIETARY_SUPPLEMENTVamin (Fresenius Kabi)
Vamin 18gN 1ml/min infusion in 6 hours
DIETARY_SUPPLEMENT3hydroxybutyrate
Goldbio, FFA-3OHB, dry powder mixed with sterile water at Aarhus University hospital pharmacy.
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI between 19 and 28 * Written consent before study start
Exclusion criteria
* Diabetes * Inclusion in other studies using ionizing radiation. * Allergic to egg or soy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in muscle metabolism after administration of amino acids. | Basal period and a glucose clamp (6 hours pr.day) | Measured by arterio-venous differences of isotope tracers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracellular mTOR and pAkt signal activation after infusion of amino acids. | Basal period and a glucose clamp (6 hours pr. day) | 4 muscle biopsies measured for mTOR and pAkt activation by western blotting |
Countries
Denmark
Outcome results
None listed