Hepatic Function in Premature Lambs Supported by the Artificial Placenta and Total Parenteral Nutrition

Abstract

The artificial placenta (AP) promotes organ development and reduces organ injury in a lamb model of extreme prematurity. This study evaluates hepatic outcomes after AP support with total parenteral nutrition (TPN) administration. Premature lambs (116-121 days estimated gestational age; term = 145) were cannulated for 7 days of AP support. Lambs received TPN with SMOFlipid (n = 7) or Intralipid (n = 5). Liver function and injury were compared between the two groups biochemically and histologically. Groups were compared by ANOVA with Tukey's multiple comparisons or linear-mixed effects models. From baseline to day 7, total bilirubin (Intralipid 2.6 ± 2.3 to 7.9 ± 4.4 mg/dl; SMOFlipid 0.3 ± 0.1 to 5.5 ± 2.3 mg/dl), alanine aminotransferase, and gamma-glutamyl transferase increased in both groups ( p < 0.001 for all). Direct bilirubin (0.3 ± 0.2 to 1.8 ± 1.4 mg/dl; p = 0.006) and AST (27 ± 5 to 309 ± 242 mg/dl; p < 0.001) increased in SMOFlipid group (not measured in Intralipid group). On liver histology, Intralipid showed more cholestasis than SMOFlipid; both groups showed more than tissue controls. The Intralipid group alone showed hepatocyte injury and had more congestion than controls. Lambs supported by the AP with TPN administration maintain normal hepatic function and sustain minimal hepatic injury. SMOFlipid is associated with decreased cholestasis and hepatic injury versus Intralipid.

Figure 1.

Schematic of the artificial placenta. Blood is drained from the right jugular vein by a passive-filling roller pump and propelled to an oxygenator/heat exchanger, then returned via an umbilical vein. The second umbilical vein is accessed for intravenous fluid and medication administration, and an umbilical arterial line is placed for hemodynamic monitoring and blood gas sampling. The lamb is intubated, and the lungs remain filled with Ringer’s Lactate or perfluorodecalin. Reproduced with permission from Church et al 2018. Ao – aorta; DV – ductus venosus; IJV – internal jugular vein; IVC – inferior vena cava; RA – right atrium; SVC – superior vena cava

Figure 2.

Graphs of average daily a) aspartate aminotransferase (AST), b) alanine aminotransferase (ALT), c) alkaline phosphatase (ALKP), d) gamma-glutamyl transferase (GGT), e) total bilirubin, and f) direct bilirubin for SMOFlipid® and Intralipid® groups over 7 days of artificial placenta support. Error bars represent standard deviation. P value < 0.05 considered statistically significant.

Figure 3:

Mean histological liver scores for SMOFlipid®, Intralipid®, ETC and LTC for Cholestasis, Hepatocyte Injury, Congestion, Fatty Change, and EMH. Error bars represent standard deviation. P values < 0.05 considered significant.