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Abstract
Background
In the absence of intestinal adaptation, neonates with short bowel syndrome (SBS) depend on long-term parenteral nutrition (PN). This can lead to recurrent sepsis, liver disease, loss of vascular access and poor quality of life. Early referral for transplantation or consideration of novel trophic therapies may be advantageous in this setting. However, current methods to assess the progress of adaptation in neonates are limited. Citrulline has been proposed to have utility as a non-invasive biomarker of intestinal adaptation.
Aims
Our goal was to evaluate plasma citrulline in two experimental models of SBS that vary in potential for adaptation.
Methods
Neonatal piglets (2 to 4 days old) were randomly allocated to either a 75% distal gut resection (jejunucolic/ JC, n=9), mid- intestinal resection (jejunoileal/JI, n= 5) or sham control (n=8). A jugular catheter was inserted for PN feeds and a gastric tube for trophic enteral nutrition. On day 7 (D7) small intestinal length and weight were measured and jejunum collected for evaluation of villus height and crypt depth. Plasma citrulline levels were measured day 0 (D0) and D7 using DC/LC-MS. Statistical analysis included independent t tests, one-way ANOVA and linear regression.
Results
In all cases average citrulline level declined D0 to D7. Including sham with the SBS piglets, citrulline level correlated with final (D7) length (p< 0.01) and with mucosal mass (p< 0.01). However, considering only SBS piglets, citrulline level did not correlate with length (p=0.68), mucosal mass (p=0.8) or jejunal villus height (p= 0.9). JI, compared to JC, demonstrated more adaptation with increased length post-resection (p <0.01) and mucosal mass (p< 0.01). However, D7 citrulline levels did not differ between the two groups (p=0.63).
Conclusions
Plasma citrulline levels do not discriminate between anatomical subtypes of short gut that vary in potential for adaptation, nor correlate with their actual adaptive changes.
| JC | JI | SHAM | P VALUE | |
|---|---|---|---|---|
| Intestine length, day 0, post resection | 140 | 155 | 583 | <0.01 |
| Intestine length, day 7 | 124 | 173 | 636 | <0.01 |
| Mucosal mass, day 7 | 7.1 | 13.2 | 27.3 | <0.01 |
| Plasma citrulline, day 0 | 2101 | 2218 | 1829 | 0.22 |
| Plasma citrulline, day 7 | 786 | 729 | 1088 | 0.04 |
| Jejunum villus height | 6.6 | 8.7 | 7.0 | 0.11 |
| Jejunum crypt depth | 1.8 | 1.7 | 1.6 | 0.30 |
Mean values shown, P value is shown using one-way ANOVA significance was set at p < 0.05. Intestinal length values in cm, Jejunum measurements each unit is 0.1 mm, citrulline levels in Pico-moles.
Funding Agencies
CIHR
Details
1 Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
2 Department of Surgery, University of Alberta, Edmonton, AB, Canada
3 Department of Pediatric Surgery, Kagoshima University, Sakuragaoka Kagoshima, Japan
4 Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
5 The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
6 Department of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, AB, Canada