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Continued Investigation Into 17-OHPC: Results from the Preclinical RUPP Rat Model of Preeclampsia

Lorena M. Amaral, Jessica L. Faulkner, Jamil Elfarra, Denise C. Cornelius, Mark W. Cunningham, Tarek Ibrahim, Venkata Ramana Vaka, Jessica McKenzie, Babbette LaMarca

Hypertension. 2017; 70: 1250-1255 PMID: 29084881

Lorena M. Amaral (USA) 

1) Summarize your work in one sentence.

We hypothesized that administration of 17-hydroxyprogesterone caproate (17-OHPC) on day 15 of gestation could improve pathophysiology of preeclampsia and fetal outcomes in response to placental ischemia.

2) Summarize your findings in one sentence.

Our study illustrates that administration of 17-OHPC on day 15 of gestation improves intrauterine growth restriction, nitric oxide bioavailability, uterine artery resistance index (UARI), possibly via reducing sFlt-1 levels and inflammation while lowering blood pressure in response to placental ischemia.

3) Which were the more important methods you used in this work? If it is not a traditional method you can briefly explain the concept of that methodology.

The important methods that we did in this work were the RUPP procedure and the measurement of uterine artery resistance index. Briefly, under 2% isoflurane anesthesia, on day 14 of gestation, the lower abdominal aorta were isolated from Sprague Dawley rats and a silver clip (0.203 mm ID) placed around the aorta above the iliac bifurcation. To prevent augmentation of blood flow to the uterus via the ovarian arteries, silver clips (0.100 mm ID) were also placed on the branches of both ovarian arteries that supply the uterus. On day 18 of gestation, Power Doppler velocimetry measurements were performed on anesthetized pregnant dams at an imaging station with a Vevo 770 unit (Visual sonics) using a 30 Hz transducer and an insonation angle <30°. The peak systolic flow velocity (PSV) and end diastolic flow velocity (EDV) were recorded using the uterine artery Doppler waveform and the index was calculated using the following formula: UARI= (PSV-EDV)/PSV

4) What did you learn from this paper, what was your take-home message?

Early administration (GD15) of 17-OHPC not only improves inflammation and sFlt-1, but it also reduced UARI and increased NO. This could be the mechanism for the further reduction in blood pressure compared with that seen with GD18 administration. Importantly fetal characteristics such as fetal weight and litter size were significantly increased suggesting earlier intervention with 17-

OHPC could have beneficial effects to not only improve maternal outcome but that of the baby, via improvements in the sFlt-1/NO pathway, and should be considered for the addition to the management of PE clinically.


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