Research Assistant II Monroe Carell Jr. Children's Hospital at Vanderbilt Manchester, Tennessee, United States
Background: Patent ductus arteriosus (PDA) is one of the most common neonatal cardiovascular disorders. DA closure after birth may be disrupted by a variety of factors. PDA is over-represented in RDS, and surfactant exposure is associated with PDA in many RCTs of exogenous surfactant. Ductus diameter increases after intratracheal surfactant administration in some studies, and surfactant has been shown to relax airway smooth muscle. Thus, exogenous surfactants may directly contribute to PDA, but this has never been examined. Objective: We hypothesized that exogenous surfactant has a vasodilatory effect on the isolated mouse DA and impairs responses to constrictive postnatal signaling mechanisms. Design/Methods: CD-1 pups were delivered by C-section on gestation day 19 (term). Fetal DAs were isolated, mounted, and pressurized to physiologic tone in microvessel perfusion chambers. DAs were exposed to increasing concentrations of each surfactant or its components under deoxygenated or oxygenated conditions while intraluminal diameter was continuously recorded (Ionoptix). DA diameter before drug addition was designated either as resting baseline (deoxy) or O2-preconstricted baseline, and percent change was calculated. Data were analyzed by t-test or one-way ANOVA; p < 0.05 was considered significant. Results: Poractant alfa induced significant DA dilation under both oxygenated (118% reversal) and deoxygenated (22% change) conditions. In contrast, isolated DAs either had no response (BLES, calfactant) or were constricted by some surfactants (beractant (-17% change), SynSurf (-39% change)). Poractant, but not other surfactants, impaired O2-induced DA constriction. Paired exposures in the same vessel confirmed significant DA dilation in response to poractant but not other surfactants. DA tone was not affected by common constituents of surfactant such as phosphatidylglycerol, phosphatidylethanolamine, KL-4 or SP-B, but was constricted by DPPC (-18%). Inhibition of NO synthesis partially blocked (20% inhibition) the vasodilating effects of poractant alfa.
Conclusion(s): Poractant alfa had a small but significant dose-dependent dilating effect and prevented O2-induced constriction of the isolated mouse DA. Surfactant-induced changes may involve NO signaling, but other mechanisms are untested. Plausibility for surfactant effects on the human DA are known from prior echo studies, but do not explain how intratracheal surfactant components reach the DA, which requires additional studies. Synthetic surfactants might avoid this effect and be a better choice for managing RDS in PDA-susceptible neonates.
