Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

A Comparison of the Cardiovascular Effects of Dopamine and Sildenafil between Growth Restricted and Appropriately Grown Preterm Lambs (#3)

Ishmael M Inocencio 1 , Beth J Allison 1 , Ilias Nitsos 1 , Valerie Zahra 1 , Suzanne L Miller 1 , Graeme R Polglase 1
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton , VIC, Australia

Introduction:
Fetal growth restricted (FGR) infants have increased risk of cardiovascular (CV) complications in early life, secondary to prolonged CV adaptations to fetal hypoxia. Consequently, FGR infants require greater postnatal support compared to appropriate grown (AG) counterparts1. Dopamine (DOP), a β-agonist, is commonly used to support CV function in preterm infants. However, efficacy is limited in FGR neonates2. We have previously shown deficiencies in vascular nitric oxide (NO) in FGR preterm lambs3. As sildenafil (SC) can potentiate NO, we hypothesize that SC will provide greater CV support to preterm FGR lambs compared to DOP.

Methods:
Preterm lambs (0.6GA) underwent sterile surgery for single umbilical artery ligation (FGR) to induce FGR or sham (AG) surgery. Fetuses are exposed via caesarean section at 0.8GA to implant monitoring equipment. Lambs were delivered and ventilated for 4h. 1h post-delivery, lambs received i.v SC (FGRSC,n=6/AGSC,n=8), DOP(FGRDOP,n=6/AGDOP,n=7) or saline (FGR,n=6/AG,n=7). CV physiology was continuously monitored. Mixed-effects analysis was used to compare data and a Tukey’s test was to determine multiple comparisons between groups.

Results:
Figure 1 shows the BP and HR response of SC and DOP groups. 15 min following treatment, BP transiently, but significantly, decreased in FGRSC but not AGSC lambs. HR was not different in FGRSC or AGSC lambs. No immediate response to BP and HR was observed in FGRDOP or AGDOP lambs. However, BP and HR significantly decreased in FGRDOP 2h post-treatment compared to baseline. Plasma troponin significantly increased in FGRDOP compared to all other groups. BP and HR were unchanged in FGR/AG.

Conclusions:
SC had a transient adverse effect to CV function in FGR. DOP does not maintain CV function in FGR and may increase cardiac injury. This may underlie the limited efficacy of dopamine treatment seen clinically.

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  1. 1. Malhotra, A. et al. Front. Endocrinol. (Lausanne). 10, 1–18 (2019).
  2. 2. Seri, I. J. Perinatol. 26, S8–S13 (2006).
  3. 3. Polglase, G. R. et al. Pediatr. Res. 80, 538–546 (2016).