Pregnancy is associated with physiologic vasodilation. We have defined, using Doppler ultrasound in cerebral arteries, some of the physiologic changes in blood velocity and resistance during normal pregnancy. Preeclampsia, an ubiquitous endothelial disease, causes vasospasm and an increase in arterial resistance. Increased vascular reactivity predates the clinical syndrome (hypertension/proteinuria) by weeks or months. Based on this, a number of tests have been studied for their ability to predict preeclampsia, but currently none that are clinically useful. We have identified distinct differences in cerebral/orbital Doppler parameters between preeclamptic and normotensive pregnant women. Furthermore, we have developed 3 Doppler analytical models which can be used to reliably differentiate between term normotensive and preeclamptic women using cerebral arterial resistance indices and estimated cerebral perfusion pressure. These models can be adapted to other vascular beds including the renal, uteroplacental and peripheral arterial circulations. Our objectives in this proposal are to show that simultaneous Doppler studies of small arteries in a number of vascular beds can (i) identify preeclampsia in its preclinical and subclinical phases, and (ii) group patients with established preterm preeclampsia into those who will fail or respond to conservative temporizing management. We will use standard Doppler methods in the cerebral, orbital, renal, uteroplacental and peripheral arterial beds to determine derived resistance, flow-velocity, and perfusion indices. In addition dynamic tests of vascular reactivity will be used to differentiate stress profiles. Two longitudinal protocols are planned: A: an outpatient study of 320 low-risk, primigravid women, evaluated monthly from 16 weeks or less until term/delivery, and then at 6, 12 and 24 weeks postpartum; B: an in-house protocol of 30 preterm preeclamptics undergoing temporizing management, evaluated on a daily basis initially, and once stable every other day, until delivery. Early detection of abnormal arterial function may allow identification of preeclampsia before emergence of clinical signs. In established preeclampsia, evidence of worsening vasospasm will provide information on the course of the disease and the effectiveness of the therapy being employed.
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