sildenafil-citrate and Placental-Insufficiency

To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR).. This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples.. There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia.. The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Topics: Administration, Cutaneous; Adult; Blood Flow Velocity; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Middle Cerebral Artery; Nitroglycerin; Placental Insufficiency; Pregnancy; Prospective Studies; Pulsatile Flow; Sildenafil Citrate; Treatment Outcome; Ultrasonography, Prenatal; Umbilical Arteries; Uterine Artery; Vasodilator Agents; Young Adult

Sildenafil is a potential new treatment for placental insufficiency in human pregnancies as it reduces the breakdown of vasodilator nitric oxide. Pulmonary vasodilatation is observed in normoxemic fetuses following sildenafil administration. Placental insufficiency often leads to fetal hypoxemia that can cause pulmonary vasoconstriction and fetal cardiac dysfunction as evidenced by reduced isovolumic myocardial velocities. We tested the hypotheses that sildenafil, when given directly to the hypoxemic fetus, reverses reactive pulmonary vasoconstriction, increases left ventricular cardiac output by increasing pulmonary venous return, and ameliorates hypoxemic myocardial dysfunction. We used an instrumented sheep model. Fetuses were made hypoxemic over a mean (standard deviation) duration of 41.3 (9.5) minutes and then given intravenous sildenafil or saline infusion. Volume blood flow through ductus arteriosus was measured with an ultrasonic transit-time flow probe. Fetal left and right ventricular outputs and lung volume blood flow were calculated, and ventricular function was examined using echocardiography. Lung volume blood flow decreased and the ductus arteriosus volume blood flow increased with hypoxemia. There was a significant reduction in left ventricular and combined cardiac outputs during hypoxemia in both groups. Hypoxemia led to a reduction in myocardial isovolumic velocities, increased ductus venosus pulsatility, and reduced left ventricular myocardial deformation. Direct administration of sildenafil to hypoxemic fetus did not reverse the redistribution of cardiac output. Furthermore, fetal cardiac systolic and diastolic dysfunction was observed during hypoxemia, which was not improved by fetal sildenafil treatment. In conclusion, sildenafil did not improve pulmonary blood flow or cardiac function in hypoxemic sheep fetuses.

Topics: Animals; Cardiac Output; Disease Models, Animal; Female; Hemodynamics; Hypoxia; Placental Insufficiency; Pregnancy; Pulmonary Circulation; Sheep; Sildenafil Citrate; Vasodilator Agents