(OR07-03-24) Non-essential Amino Acids Are Needed to Attenuate ICU Acquired Muscle Weakness (ICU-AW) in a Pig Model of Sepsis Recovery

Objectives: Sepsis leads to long-term muscle weakness, fatigue, and reduced physical activity (ICU-AW). We developed an acute sepsis-recovery ICU-AW pig model to study whether meals with essential (EAA) or all amino acids (TAA) improve muscle function recovery and restore amino acid metabolism differently.

Methods: In 49 pigs (± 25 kg), sepsis was induced by i.v. live Pseudomonas Aeruginosa bacteria (5*10⁸ CFU/hour). At t=9h, recovery was initiated with i.v. gentamicin. Post sepsis, twice daily food was given incrementally (Day1:25%, 2:50%, 3:75%, 4:7:100%). The 100% meals contained per kg BW: 15.4gr CHO and 3.47gr fat per kg BW, and a balanced free TAA (reflecting muscle) or EAA mixture (0.56 gr N: EAA or TAA group). We measured involuntary, isometric pelvic limb muscle strength before and at Day3&7. Peak force and downslopes of the fatigue curves were obtained from tetanus stimulations of the tibiotarsal muscles. Postabsorptive plasma amino acid (AA) concentrations by LC-MS/MS and two-way RM-ANOVA (time (sepsis recovery), intervention (nutrition), and interaction) (𝜶=0.05).

Results: A body weight reduction was found after sepsis in both groups, which was restored at day7 post sepsis.

Muscle Flexion: no (p >0.2) time, intervention or interaction effects in strength, but higher in EAA at day7 (p=0.0319). Fatigue increased over time (p=0.0008) and more in EAA (p=0.0045). TAA had 30% less fatigue at day7 (p < 0.0001) whereas EAA had more fatigue at day3 and 7 (p < 0.0002).

Muscle Extension: no time or intervention effects in strength or fatigue.

Plasma EAA changes were related to meal AA composition, whereas in response to TAA, non-essential AA (NEAA) showed ARG (p < 0.0001) and CIT (p=0.0009) higher, and GLN (p < 0.0001), GLU (p < 0.0001) and TAU (p < 0.0001) lower. In EAA, lower ARG (p=0.0095) and TAU (p=0.0021; more in EAA: p< 0.0001), unchanged GLN (p=0.97) and increased CIT (p < 0.0001; more in EAA: p< 0.0008). Tau-methylhistidine, a product of myofibrillar protein breakdown, increased by 56% in EAA (Day 3 and 7; p< 0.004).

Conclusions: Our chronic instrumented sepsis-recovery pig ICU-AW model therefore shows that providing an incremental TAA meal (EAA + NEAA) attenuates muscle fatigue more than EAA meal and possibly reduces protein breakdown. We hypothesize that providing certain NEAA with EAA may play a key role in attenuating ICU-AW.

Funding Sources: DOD PR190829 (W81XWH-20-1-0259)