Pulsatile arterial load in preeclampsia

Magee-Women'S Res Inst And Foundation, Pittsburgh PA

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Abstract

Changes in pulsatile arterial load (PAL) early in gestation (e.g., increased global arterial compliance, AC) play an important adaptive role in normal pregnancy (e.g., minimize arterial pressure and flow pulsatiles) and preliminary data suggest that aberrant PAL responses may be involved in the pathophysiology of preeclampsia. Working model: AC does not increase early in gestation in subjects destined to develop preeclampsia resulting in increased arterial pressure and flow pulsatiles, and consequently, increased pulsatile (oscillatory) shear stress at vascular endothelium, which is known to cause a sustained activation of endothelial pro-oxidant processes. Over time, this sustained endothelial dysfunction and/or inadequate compensation by anti-oxidant defenses can lead to the hemodynamic milieu commonly seen with the onset of the clinical syndrome of preeclampsia (high blood pressure; high systemic vascular resistance, SVR; and normal-to-low cardiac output). Thus, the focus of the present proposal is to comprehensively examine systemic arterial and left ventricular (LV) properties in primiparous control and prior preeclamptic women, both in the non- pregnant state and throughout the second gestation. Hypotheses: 1) In subjects with a history of preeclampsia, differences in vascular mechanical properties (PAL in particular) and/or endothelial function exist in the non-pregnant state and chronic anti-oxidant therapy(vitamin C supplementation) can help reduce these differences. 2) In subjects destined to develop preeclampsia, the increase in AC during early gestation, which is seen in normal pregnancy, is significantly attenuated. Two groups of primiparous women will be studied at 6-12 months post- partum (Aim 1a): i) prior preeclamptic subjects (n=70, Group 1) and ii) control subjects (n=70, Group 2). Group 1 subjects will be restudied following an 8-week supplementation with either vitamin C (N=35) or placebo (n=35) (Aim 1b). Finally, a longitudinal study will be conducted in two groups of primiparous women (pre-conception-during second gestation-post-partum) (Aim 2): i) prior preeclamptic subjects (n=70) and ii) control subjects (n=15). Non-invasive measurements will be performed to quantify arterial properties (global: aortic input impedance spectrum, SVR, AC, wave reflection indices; regional: pulse wave velocity, pressure-diameter relationships, indices of vessel wall stiffness), LV properties (size, shape, and mass, indices of myocardial contractility), and endothelial function (forearm blood flow response to mental stress). Blood and urine samples will be analyzed to derive indices of endothelial activation, oxidative stress, and dyslipidemia. Results of these studies are expected to provide insights into the role of pulsatile arterial load in the pathogenesis of preeclampsia.