SPLANCHNIC GLUTAMINE METABOLISM IN PRETERM INFANTS

Recent animal and human research, including studies in neonatal preterm
infants, have demonstrated that intestinal amino acid utilization not only has
a major impact on dietary amino acid availability, but that amino acids play a
critical and specific role in intestinal metabolism. In a general sense, the
rate of amino acid utilization by the intestine will determine their systemic
availability and, as such, the magnitude of intestinal metabolism could be an
important regulator of whole-body protein accretion. Studies in milk
formula-fed neonatal piglets have shown that as much as half of the dietary
protein intake is utilized by the portal drained viscera (stomach, pancreas,
spleen, duodenum and colon; PDV), and that the energy needed to sustain the
high rate of protein turnover in the gut is largely derived from the oxidation
of amino acids. Glutamine is described as a conditionally essential amino acid
for critically ill patients, and glutamine is important in several key
metabolic processes of immune cells and enterocytes. There is also considerable
evidence that glutamine can enhance the barrier function of the gut, which is
of particular importance in preterm neonates which can be seen immunological
vulnerable patients.
The present study is designed to quantify, in preterm infants, the splanchnic
uptake and catabolism of dietary glutamine, to determine whether glutamine is
one the major substrates for energy in the gut of the preterm infants.

1. To determine the rate of splanchnic utilization of glutamine, proposed to be
conditionally essential for premature infants.
2. To quantify the rate of splanchnic oxidation of dietary glutamine, which is
supposed to be one of the major fuel subtrates for the intestinal tissues.

At 07.30 h on each study day two baseline breath samples and a baseline blood
sample will be obtained for measurement of background isotopic enrichment. The
breath samples are collected according the method described by Van der Schoor.
A nasal prong (6Fr) (Argyle, Sherwood Medical, Petit Rechain, Belgium) will
briefly be placed in the nose and 10 ml end-tidal breath is sampled slowly with
a syringe. The breath samples will be stored in vacutainers. Blood samples (0.5
ml) will be withdrawn from the arterial catheter, if present, or by heelstick.
The baseline bloodsample in the morning will be combined with routine blood
sampling. At 08.00 h a priming dose of the [1-13C]bicarbonate infusion (10 µmol/
kg) will be given first followed by a 2 hours [1-13C]bicarbonate infusion (10
µmol/kg) to measure the CO2 production rate. Following this [1-13C]bicarbonate
infusion, a labeled glutamine infusion will be started intravenously
simultaneously with a different labeled form of the same amino acid tracer
intragastrically. At the start of the glutamine tracer infusion (t = 120 min)
priming doses of the tracers are given by their respective routes. Both the
enteral and the intravenous tracer infusions will be continued at a constant
rate for 5 h. After 390 min one bloodsample (0.5 ml) will be taken in
combination with routine blood sampling. At the end of each study day at 420
min one blood sample (0.5 ml) will be taken for determination of plasma
enrichments. The total volume of blood sampled will therefore be 3.0 ml, which
is <2.5% of blood volume in a 1,500 g baby.

Tracer protocol

Infusionscheme study: Glutamine metabolism (n=10 infants)

Study day 1:
0-2 h [1-13C]Na-bicarbonate intravenous 10 µmol/kg/h
2-7 h [ U-13C]glutamine 30 µmol/kg/h intragastric
2-7 h [15N]glutamine 30 µmol/kg/h intravenous

Study day 2:
0-2 h [1-13C]Na-bicarbonate intravenous 10 µmol/kg/h
2-7 h [15N]glutamine 30 µmol/kg/h intragastric
2-7 h [ U-13C]glutamine 30 µmol/kg/h intravenous

not applicable.