Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis

Abstract

Although glucose and protein metabolism have been investigated extensively in experimental models of hypodynamic sepsis, relatively little information is available regarding the compensated stage of sepsis. We investigated interorgan amino acid and glucose metabolism in a porcine model of compensated hyperdynamic sepsis. Fasting catheterized pigs received endotoxin ( Escherichia coli lipopolysaccharide; 3 microg.h(-1).kg(-1); intravenous) or saline (controls) and volume resuscitation over 24 h to reproduce hyperdynamic sepsis. Primed-constant infusions of p -aminohippurate and (3)H-labelled isotopes were used to measure glucose, amino acid and protein metabolism across the portal-drained viscera, liver and hindquarters (to represent muscle) at 0 and 24 h of endotoxaemia. Whole-body protein and glucose flux were increased during hyperdynamic compensated sepsis. In endotoxaemic pigs, visceral protein was conserved, and hindquarter protein breakdown exceeded the increase in liver protein synthesis, resulting in net whole-body protein loss. Endotoxaemia increased hindquarter and visceral glycolysis and branched-chain amino acid transamination. The rate of efflux of glutamine and alanine from the hindquarters was higher than anticipated from protein breakdown, indicating de novo synthesis of these amino acids during endotoxaemia. In addition to the hindquarters, the portal-drained viscera provided substantial gluconeogenic amino acids and lactate to the liver. Although increased liver glutamate release constitutes an important nitrogen-sparing mechanism and carbon skeletons are effectively being cycled in glucose, net body protein is lost through increased ureagenesis during the hyperdynamic stage of sepsis. Specific amino acid requirements may develop in compensated hyperdynamic sepsis that is characterized by maintained organ perfusion and increased substrate utilization at the expense of body protein.

Impacts of chronic and increasing lipopolysaccharide exposure on production and reproductive parameters in lactating Holstein dairy cows

“…Increased circulating MUN in LPS-AL cows is in alignment with the circulating BUN data (see companion paper; Horst et al, 2019). We speculate these makers of protein metabolism indicate endotoxemia-induced increased skeletal muscle catabolism, commonly reported in monogastrics (Bruins et al, 2003;Iseri and Klasing, 2013). However, interpreting circulating urea dynamics in ruminants is complicated due to the contribution of rumen-derived ammonia and the confounding effect systemic LPS has on changes to the rumen microbiome (Jing et al, 2014).…”

Porcine Models of Severe Sepsis: Emphasis on Porcine Peritonitis

“…Fluid resuscitation in porcine severe sepsis models 2 liters per in the first hour, 1 liter per hour thereafter (11) 75 ml/kg/hr crystalloid (9) 40 ml/kg/hr crystalloid (12) 20 ml/kg/hr crystalloid (13) 18 ml/kg/hr crystalloid (6) 5 ml/kg/hr crystalloid (7) 2000 ml day 1 and then 1000 ml day crystalloid (14) Up to 15 ml/kg/hr colloid to maintain CO 80% of baseline (7) Colloid to maintain MAP $ 60 mm Hg (15) None or not mentioned (12,19,20) Na Bicarbonate to maintain base deficit mmol/L (9) converted into glucose, while amino groups are used in ureagenesis, resulting in net nitrogen loss excreted as urea. Bruins et al (29) used fasting pigs receiving intravenous E. coli and volume resuscitation over 24 h to reproduce hyperdynamic sepsis. Glucose amino acid and protein metabolism were measured across the portal-drained viscera, liver, and hind quarters.…”

Role of specific dietary amino acids in clinical conditions

“…further blood acidification and increase in plasma urea concentration). Endogenous non-EAAs are generally available in excess during sepsis because of accelerated release from muscle protein catabolism ( 79 ) and increased de novo synthesis resulting from oxidation of dietary EAAs ( 79 ) . Therefore, we anticipate that, as shown in elderly populations, only dietary EAAs are necessary in acute critical illness to improve net protein synthesis and would be beneficial above complete amino acid mixtures by reducing the chance of adverse effects.…”