Glutamine-containing dipeptides as infusion substrates in the septic state

Area of Science:

• Nutritional biochemistry
• Surgical research
• Metabolic studies

Background:

• Lowered intracellular glutamine concentrations in skeletal muscle are linked to reduced protein synthesis rates.
• Sepsis and surgical stress can lead to significant depletion of muscle glutamine stores.
• Glutamine supplementation is explored as a therapeutic strategy to mitigate these effects.

Purpose of the Study:

• To investigate the efficacy of parenteral nutrition supplemented with glutamine or glutamine dipeptides (alanylglutamine, glycylglutamine) in repleting skeletal muscle glutamine pools in septic dogs.
• To assess the impact of these nutritional interventions on hind limb glutamine exchange during postoperative sepsis.
• To determine if glutamine dipeptides offer an advantage over free glutamine in maintaining glutamine levels.

Main Methods:

• Sepsis was induced in dogs after surgery and a 48-hour fast.
• Dogs received isocaloric and isonitrogenous parenteral nutrition for 48 hours, supplemented with either free glutamine, alanylglutamine, or glycylglutamine.
• Intracellular glutamine concentrations in skeletal muscle and hind limb glutamine exchange were measured.
• Physiological markers of sepsis, including plasma protein, platelet count, and leukocyte count, were monitored.

Main Results:

• Starvation significantly decreased muscle free glutamine levels by 41%.
• Postoperative sepsis was characterized by hypoalbuminemia, thrombocytopenia, leukocytosis, and positive blood cultures.
• None of the tested glutamine-containing solutions effectively replenished skeletal muscle glutamine pools within 48 hours.
• Alanylglutamine and its constituent amino acids significantly reduced hindquarter glutamine release, while glycylglutamine did not alter it.

Conclusions:

• The administered dose and duration of glutamine supplementation (equivalent to 26g/day for a 70kg person) were insufficient to restore skeletal muscle glutamine deficiency in septic, depleted dogs.
• Glutamine dipeptides, particularly alanylglutamine, influenced glutamine release from muscle but did not prevent overall depletion.
• Further research is needed to determine optimal glutamine dosing strategies and durations for clinical conditions involving muscle glutamine depletion.