Abstract
Background
Apelins are potential candidate therapeutic molecules for hemodynamic support. The objective of this study was to assess the hemodynamic impacts of apelin-13 in a neonatal lamb model of septic shock.
Methods
Lambs were randomized to receive apelin-13 or normal saline. Septic shock was induced by injecting a fecal slurry into the peritoneal cavity. Lambs underwent volume repletion (30 mL/kg over 1 h) followed by intravenous administration of 5 incremental doses (D) of apelin-13 (D1 = 0.039 to D5 = 19.5 µg/kg/h) or normal saline.
Results
Following fecal injection, mean arterial pressure (MAP) and cardiac index (CI) dropped in both groups (p < 0.05). The MAP decreased non-significantly from D1 to D5 (p = 0.12) in the saline group, while increasing significantly (p = 0.02) in the apelin group (−12 (−17; 12) vs. +15 (6; 23) % (p = 0.012)). Systemic vascular resistances were higher in the apelin-13 group at D5 compared to the saline group (4337 (3239, 5144) vs. 2532 (2286, 3966) mmHg/min/mL, respectively, p = 0.046). The CI increased non-significantly in the apelin-13 group.
Conclusion
Apelin-13 increased MAP in a neonatal lamb septic shock model.
Impact
-
Administration of apelin-13 stabilized hemodynamics during the progression of the sepsis induced in this neonatal lamb model.
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Systemic vascular resistances were higher in the apelin-13 group than in the placebo group. This suggests ontogenic differences in vascular response to apelin-13 and warrants further investigation.
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This study suggests that apelin-13 could eventually become a candidate for the treatment of neonatal septic shock.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Funding
This study was funded internally (CRC-CHUS, Projets de Recherche Structurants, 2019). It was also supported by the Canadian Institutes of Health Research (CIHR) – Project grants (376770, 389979, and 399567), and the Senior Investigator Award of the Faculty of Medicine (FMSS) (O.L.).
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Conception and design: E.S., D.C., C.N., N.S., J.-P.P., O.L., E.F.-P. Data acquisition: E.S., C.M., D.C., C.N., N.S., E.F.-P. Analysis and interpretation: E.S., D.C., J.P.-P., O.L., E.F.-P. Drafting the article: E.S., E.F.-P. Final approval: E.S., C.M., D.C., C.N., N.S., J.P.-P., O.L., E.F.-P.
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Simard, É., Morin, C., Coquerel, D. et al. Hemodynamic impacts of apelin-13 in a neonatal lamb model of septic peritonitis. Pediatr Res 94, 129–134 (2023). https://doi.org/10.1038/s41390-022-02407-y
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DOI: https://doi.org/10.1038/s41390-022-02407-y
