Impairments in Protein Digestion and Absorption Attenuate the Anabolic Response to Feeding in Patients with Congestive Heart Failure (FS09-03-19)

Abstract

Abstract Objectives Gastrointestinal symptoms are prevalent extracardiac systemic manifestations of Congestive Heart Failure (CHF). We developed a comprehensive panel of methods to unravel gut dysfunction in CHF and its impact on the anabolic response to feeding. Methods We recruited 14 clinically stable CHF patients (ejection fraction: 33.9 ± 2.1, NYHA class: 2.3 ± 0.2) and 17 healthy controls matched for age and gender. Stable tracers of L-phenylalanine (PHE)-[ring-2H5] and L-tyrosine (TYR)-[13C9,15 N] were administered intravenously for 5 hours via primed constant and continuous infusion. After 2 hours, participants ingested a complete high protein meal containing L-PHE-[1–13C] and spirulina-[U-15 N]. We sampled blood throughout the study to analyze enrichments by LC-MS/MS. We calculated the anabolic response to feeding before and after correction for changes in protein digestion and absorption, assessed by spirulina degradation ratio (L-PHE-[15 N]/[1–13C]). Moreover, we measured small intestinal membrane integrity and active carrier-mediated glucose transport by urinary recovery of the orally ingested inert sugars lactulose, rhamnose, and 3-O-methyl-glucose. Disease severity was assessed by medical chart and history. Statistical analysis was performed by unpaired t-tests. Data are expressed as mean ± SEM. Results In CHF patients, protein digestion and absorption were reduced (0.66 ± 0.04 vs. 0.82 ± 0.04, P < 0.01), which further attenuated the anabolic response to feeding (28.3 ± 3.8 vs. 54.0 ±5.5 μmol/kg FFM/meal, P < 0.001). Disturbances in protein digestion and absorption as well as anabolic response in CHF were independent of disease severity. Small intestinal permeability and active carrier-mediated glucose transport did not differ between the groups indicating a preserved enterocyte function in CHF patients. Conclusions We hypothesize that enhancing protein digestion and absorption in patients with CHF can improve the availability of nutrients and protein anabolism. Funding Sources National Institutes of Health