Computer modelling and wave intensity analysis of perinatal cardiovascular function and dysfunction

Recent experimental work has highlighted a number of complex issues relating to blood ow dynamics in the normal fetus, where the structure and function of the cardiovascular system di ers substantially from the normal adult or neonate. Neonates with congenital heart disease may also display quite complex haemodynamics due to a persistence of some features of the fetal circulation after birth, along with heart and vascular abnormalities that disturb normal blood ow patterns. For example, in pulmonary atresia with intact ventricular septum (PAIVS), the right ventricular out ow path fails to develop, while the combination of an underdeveloped right ventricle and profound coronary abnormalities may give rise to quite unusual coronary arterial ow patterns. This thesis employs two research tools that are ideal for clarifying the processes that govern haemodynamics in these contexts. The rst is computer modelling, in which cardiac and vascular variables and con guration can be directly manipulated in a simulated physiological system without ethical concern. The second is wave intensity analysis, which is a powerful technique for discerning the origin of pressure/ ow waves, as well as wave interactions, that occur at or between di erent vascular measurement sites. To enable investigation of a wide range of circulatory interactions in the perinatal period, this thesis describes computer models of the entire circulation for the normal fetus and neonate, these being derived from a model of the adult circulation that also provides an essential haemodynamic reference point. The normal fetal and neonatal models are adapted to form a model of PAIVS, which includes commonly occurring coronary abnormalities such as a stula connecting to the right ventricular cavity and an interruption of the normal aorto-coronary pathway. These `comprehensive' models contain all of the major functional and anatomical segments of the circulation, including one-dimensional (1D) representations of the arterial and venous networks, and lumped parameter (0D) representations of the heart, valves and microvascular beds. In combination with wave intensity analysis and available experimental data, the normal fetal model is used to further investigate the determinants of the distinctive pressure/ ow waveforms and wave intensity patterns in the pulmonary trunk, proximal branch pulmonary arteries and ductus arteriosus that have been observed in recent experimental studies in fetal lambs. Additionally, the fetal model is harnessed to investigate factors that contribute to a so-called fetal right-ventricular dominance, and to delineate the likely physical basis of mean aorto-pulmonary pressure di erences and a functional separation of the upper body and lower body circulations in the fetus. The model of neonatal PAIVS is then used to elucidate the determinants of coronary arterial blood ow patterns and regional myocardial perfusion in the presence or absence of coronary abnormalities, both before and after surgical opening of the right-ventricular out ow path. The potential for coronary collateral connections to provide protection against myocardial ischemia is also explored. The ndings of this thesis underscore the potential for both computer modelling and wave intensity analysis to provide insights into complex haemodynamic interactions that may occur normally or abnormally in the perinatal period.