Modulation of the plasma volume compartment by aerobic exercise in women at risk for hypertensive reproductive complications

In the Netherlands almost 15.000 women each year develop hypertensive
complications like preeclampsia during their first pregnancy. In the western
world these complications account for the most substantial attribution to
neonatal and maternal morbidity and mortality. The exact etiology of this
disease cascade is still unknown. There is accumilating evidence that
subclinical abnormalities and preexistent haemodynamic, haemostatic and
endothelial factors are involved, and thought to have negative impact on
placental and endothelial functioning. The same factors are found to be risk
factors for cardiovascular incidents and therefore it is not suprising that
remotely these women are more at risk for hypertension, cardiovascular disease
and stroke. Plasma volume has possibly a central role in the disease cascade,
resulting in decreased cardiovascular reserve capacity. Furthermore a low
plasma volume is found to be a strong predictor for recurrence of hypertensive
complicated pregnancy. Adaptation, like in pregnancy, is for a large extent
depending on the functioning of the venous compartment. In formerly
preeclamptic women with low plasma volume is the venous compliance and
capicitance decreased, furthermore there is sympathic hyperactivity. This
combination reflects a decreased cardiovascular reserve capacity. These women
with low plasma volume show a reduced ability to adapt their cardiovascular
system to a new pregnancy.
It is known that physical exercise increases plasma volume in healthy adults,
also arterial and both venous compliance and capicitance is improved by
exercise. Since abnormal circulatory functions are common in formerly
preeclamptic women, we want to study the effects of exercise in this specific
group, and compare these results with women after an uneventful pregnancy. In
preventive perspective it would be beneficial that also formerly preeclamptic
women show a circulatory adaption to aerobic exercise, possibly they could
improve their haemodynamic profile prior to their pregnancy.

Primary objective:

• To investigate whether physical exercise prior to pregnancy in formerly
preeclamptic women results in a comparable improvement of vascular and
endothelial functioning as in women who had an uneventful pregnancy.

Secondary objectives:
• Which cardiovascular and endothelial parameters are involved in the vascular
adaptation to training in women with a history of preeclampsia.
• To study the vascular adaptation in the (next) pregnancy in women with a
history fo preeclampsia compared with women with a history of an uncomplicated
pregnancy, after improvement of their physical condition by exercise training.

This study is important in order to get a better understanding of the vascular
and endothelial factors involved in preeclampsia and the effects of training on
this profile. Results of this study can contribute to the improvement of
preventing hypertensive complications in pregnancy and reduction of life time
risk of cardiovascular disease in formely preeclamptic women.

To achieve these goals we defined the following hypotheses:
- Formerly preeclamptic women are/have compared to women with a history of an
uneventful pregnancy:
1. have a decreased capability to expand their plasmavolume compartment by
aerobic exercice
2. a: have a decreased capability to increase their venous compliance and
capicitance by aerobic exercise
b: have a decreased capability to mobilize unstressed venous volume in
reaction to orthostatic stress
3 have a decreased capability to reduce sympathic hyperactivity by aerobic
exercise
4.have a decreased capability to improve their arterial functioning by
aerobic exercise
5.have a reduced exercisetollerance and have a decreased capability to
improve this by aerobic exercise

- Formerly preeclamptic women with low plasmavolume are compared with women who
had an uneventful pregnancy less capable of adapting their venous and arterial
system to the new pregnany but can improve this by physical exercise

Prospective intervention study, with follow-up of patients after the
intervention period of 12 weeks

Aerobic training (twice weekly, à 50 minutes); training is customized to
personal physical condition (70% VO2 max). Trainingsperiod: 12 weeks

The burden for participants is mainly the time intensiveness of the study
(training twice a week and three measurements in twelve weeks time.
The measurements are minimal invasive, minimalized to two iv lines in both
forearms.

There is no medication given that is aimed to have health effects. To study the
vascular and endothelial function, 3 substances are given (voluven, dextran and
glyceryl trinitrate), these substances are well known and are without any known
medical risks, although it is known that humans can react allergic to dextran.
The dosage of dextran used in this study is low, therefore unwanted reactions
can be expected to be mild. In case of reaction, further administration will be
prevented. The insufflation of the cuffs around arm and leg are unpleasant.

Risks associated with this study is considered to be minimal.