Cardiovascular changes during orthostatic stress in women with a vascular complicated obstetric history or recurrent miscarriage

A low plasma volume is a common characteristic of women in a pregnancy
complicated by preeclampsia1. In more than half these women plasma volume
remains subnormal after delivery, without compensatory neurohumoral changes2-4.
A chronic lower plasma volume is associated with reduced venous compliance and
capacitance5, and a higher resting sympathetic activity and a lower baroreflex
sensitivity6, 7.
Functionally, a low plasma volume may affect the venous reserve capacity. Under
basal conditions * of the plasma volume is localized in the venous
compartment8. About 60% is hemodynamically inactive (unstressed volume) and
reflects the venous reserve capacity9. The unstressed volume is mobilized in
situations when the demand is increased, such as in physical exercise or during
orthostasis.
During exercise, women with low plasma volume demonstrate a reduced ability to
raise stroke volume, leaving cardiac output primarily modulated by changes in
heart rate10. Therefore, a chronic low total plasma volume most likely
primarily affects the unstressed volume and thereby lowers the venous reserve
capacity. This is likely to negatively affect orthostatic tolerance. Postural
change induces an initial decrease in venous return, that negatively affects
cardiac output. To ascertain adequate venous return, a compensatory increase in
hemodynamically active (stressed) volume is needed at the expense of the
unstressed volume, through venoconstriction.
In an earlier study (CMO number: 2006/111) we observed a decreasing venous
compliance during head-up tilt in healthy female volunteers. However, the
response in women with a low plasma volume (and most likely a decreased
unstressed volume), is currently unknown.
In this study, we would like to test the hypothesis that normotensive women
with a low plasma volume and a history of preeclampsia or recurrent miscarriage
exhibit less tolerance to head-up tilt, as indicated altered cardiovascular
changes in response to orthostatic stress.

To determine the cardiovascular changes in response to orthostatic stress in
women with a vascular complicated obstetric history or recurrent miscarriage.

To minimize any muscular activity, subjects will be stabilized on a comfortable
mattress on a tilt table. All participants will be subjected to orthostatic
stress with passively changing body posture from 20 degrees head down to 60
degrees head up tilt, in steps of 20* at 10 minutes intervals. Finger blood
pressure and heart rate will be measured continuously during the complete
experiment by Finometer (Finapres B.V., the Netherlands). From these data,
sympathetic activity, baroreflex sensitivity and changes in cardiac output and
stroke volume can be determined.
Venous compliance of the left forearm will be measured by strain gauge venous
occlusion plethysmography with direct intravenous pressure measurement. An
intravenous catheter will be inserted in an antecubital vein and connected to a
pressure transducer system. Venous compliance will be measured at each position
according to the INCR-method. In this method the cuff will be inflated from 0
to 40 mmHg during 1 minute. During this period, changes in forearm volume are
measured by a mercury-in-Silastic strain gauge at 6 cm distal to the
antecubital crease. Intravenous pressure is measured by the pressure transducer
system.

There is a chance of imminent fainting at (mainly) 60 degrees head-up tilt,
which will resolve immediately after changing to supine position.
Besides, volunteers can experience irritation of the finger cuff (Finometer)
and the cuff placed around the upper left arm (plethysmography). The amount of
mercury in the mercury-in-Silastic strain includes a negligibly risk for the
volunteers.
An intravenous catheter will be inserted in an antecubital vein, which has a
small chance of infection and/or haemorrhage on the place of insertion.