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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amino acids | Active Comparator | Amino acids compared to saline |
|
| 3hydroxybutyrat (3OHB) | Active Comparator | Ketone body, 3OHB compared to saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vamin (Fresenius Kabi) | Dietary Supplement | Vamin 18gN 1ml/min infusion in 6 hours |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in muscle metabolism after administration of amino acids. | Measured by arterio-venous differences of isotope tracers | Basal period and a glucose clamp (6 hours pr.day) |
| Measure | Description | Time Frame |
|---|---|---|
| Intracellular mTOR and pAkt signal activation after infusion of amino acids. | 4 muscle biopsies measured for mTOR and pAkt activation by western blotting | Basal period and a glucose clamp (6 hours pr. day) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Niels Møller, Professor, Dr.Med. | University of Aarhus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M-researchlab. MEA, Aarhus University Hospital, NBG | Aarhus C | 8000 | Denmark |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C545824 | amino-acid, glucose, and electrolyte solution |
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| 3hydroxybutyrate |
| Dietary Supplement |
Goldbio, FFA-3OHB, dry powder mixed with sterile water at Aarhus University hospital pharmacy. |
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