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107: Maternal administration of sildenafil citrate improves feto-placental arterial perfusion in an ex vivo human placental dual cotyledon model of fetal growth restriction

      Objective

      Fetal growth restriction (FGR) is a major cause of neonatal morbidity and mortality. Currently there are no antepartum treatments for FGR. Sildenafil citrate (SC), a phosphodiesterase type 5 (PDE5) inhibitor, has been investigated as a possible treatment to prolong preterm pregnancies affected by FGR. Animal and limited human studies have yielded mixed results. Using a dual perfusion placenta model we attempted to recreate a vasoconstrictive state found in many cases of FGR. The primary objective of this study was to determine if infusion of SC in the maternal circuit was able to attenuate the effects of the induced vasoconstriction in the fetal circuit. The secondary objective was to determine what types of PDE receptors are present in the human placenta.

      Study Design

      Five of twenty normal term placentas were successfully perfused in our dual cotyledon dual perfusion model. We infused U46619 a thromboxane mimetic into the maternal and fetal circuits of two isolated cotyledons. SC was then infused into the maternal circuit of the treatment cotyledon and normal buffer solution in the control. Feto-placental arterial pressures were recorded. Results were reported as a ratio of maximum fetal arterial pressure divided by minimum pressure after SC infusion. Statistical analysis was performed using a Student’s t test. Quantitative reverse-transcription PCR was performed on a normal term placenta to determine the PDE receptors.

      Results

      SC resulted in a 41.2% reduction in feto-placental arterial vasoconstriction versus 10.3% in controls (n=5, p=0.0297 Fig1). Of the five PDE receptors that SC is known to target only PDE-5 and PDE-10 were expressed in placental tissue (Fig2).

      Conclusion

      SC improves feto-placental arterial perfusion in a human dual cotyledon model of FGR. PDE5 is abundantly expressed in the human placenta. SC and other PDE5 inhibitors may be effective treatments for improving fetal blood flow in cases of FGR. This could result in prolongation of pregnancies affected by FGR.
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