Dennis AT. (2010). Cardiac function in women with preeclampsia. PhD thesis, Department of Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne (download here)
Abstract:
Preeclampsia is a major cardiovascular system disease with significant short and long term sequelae. It causes considerable morbidity and mortality in women and their babies. There is a relative lack of knowledge with respect to cardiac function in women with preeclampsia and results regarding cardiac output changes are conflicting in previous studies. Therapeutic interventions used in the management of women with preeclampsia have iatrogenic complications due to this lack of cardiovascular system knowledge.
Invasive monitoring devices such as the pulmonary artery catheter which have been used to provide information about cardiac function in historical studies, have significant risks and are currently rarely used as research tools. Their use in clinical practice is limited to the intensive care setting in extremely unwell women thus restricting their clinical applicability.
Transthoracic echocardiography, however, is routinely used in cardiovascular system research in other areas of medicine. It is frequently considered the reference standard for cardiovascular system monitoring. It is a non-invasive, precise device and is validated in pregnancy. It is an ideal device for measuring the cardiac function in women with preeclampsia however is currently rarely used in this setting.
Regarding the pathophysiology of the disease, the baboon is a non-human primate in which both mechanical and pharmacological methods of inducing preeclampsia have been developed. Transthoracic echocardiography has not previously been used as a measurement tool in this setting, however its ability to measure changes serially and after interventions offers similar advantages to those in humans.
The first aim of this thesis was to determine left ventricular systolic and diastolic function and structure in women with untreated preeclampsia, in order to determine the native disease state. The second aim was to determine the applicability of transthoracic echocardiography in the baboon for serial cardiovascular system monitoring.
Using transthoracic echocardiography, four investigations were performed; cardiac function in healthy pregnant women (Human Study 1), cardiac function in women with untreated preeclampsia (Human Study 2), cardiac function in healthy pregnant baboons (Animal Study 1), and baboon cardiac function throughout a relaxin infusion (Animal Study 2).
This thesis determined left ventricular systolic and diastolic function and structure in women with untreated preeclampsia.
The most significant finding was that of increased systolic function in women with untreated preeclampsia caused by increased cardiac output and inotropy. This occurred in the presence of abnormal diastolic function, increased left ventricular mass, increased pericardial effusions, and increased afterload. This implies that there are pathophysiological processes causing both an increase in inotropy and also vasoconstriction. This new finding allows consideration of different mechanisms for the establishment and maintenance of the pathological processes in preeclampsia, and the exploration of different aetiological mechanisms.
The other findings from this work were that transthoracic echocardiography was applicable and acceptable to healthy pregnant women and to women with preeclampsia, and was able to quantify cardiac function in almost all women. This establishes an evidence base for the use of transthoracic echocardiography in pregnant women and allows more widespread introduction of clinician based transthoracic echocardiography into routine clinical practice to measure cardiac function in pregnant women.
This technology was also able to be used to measure cardiac function in baboons. It was found to be applicable and reproducible for the assessment of systolic and diastolic function and structure in baboons. The reference ranges for baboon cardiac function, and serial changes after relaxin, were determined.