Study and Validation of a Model
of Fetoplacental Circulation


Introduction
The fetoplacental blood circulation has been object of interest for several years.
The placenta can support life and feeding of the fetus during the pregnancy: it grows up with it, and concludes its functions at the childbirth.
In particular it replaces the breathing organs, it allows the exchange of food and of waste substances, also driving the temperature of the fetus, when the central nervous system still cannot provide this function.
But, although it has been object of several years of research for its extreme importance, final answers to many questions are still pending.
For instance the microscopic structure of the placenta during the pregnancy and the internal distribution of the blood flow have not yet been totally clarified.
More complex questions, clearly not yet easy to analyse, regard the exchange of organic substances.
Answers to these questions, if reliable enough, could clarify the disputes concerned with the fetal blood oxygenation and about the causes of many pathologies of pregnancy, still with unknown aetiology.
Presently the knowledge concerning problems as IUGR (Intra-Uterine Growth Retardation), toxicology and teratology, is still lacking in sound experimental confirmations.
Moreover the clinic research doesn't allow to stride along this direction because, for ethical reasons, invasive experiments over the fetus are not proposable.
Speaking about indirect measurements, the Doppler velocimetry made it possible to describe the blood flow characteristics of the fetal side and of the maternal side of the placenta, but the presently available instruments can afford measurements affected by tolerances reaching 35% and, quite important, the reliability of the results is depending by the competence of the operator.
Research adopting direct measurement techniques, drugs and radio-active substances have been done on animals, but the results are not convincing: it was better discovered that each animal species developed a different type of circulation, during the evolution. Anyway a certain resemblance between the human and the ovine placenta has been observed.
The target of this work is to study the fetoplacental circulation through a model that has been designed mainly on the basis of the actual knowledge about the placental vessels. The most interesting point is the possibility to apply the model to modern systems of clinical analysis, to perform medical examinations able to early detect some pathologies of the pregnancy. This study was supported by the design and realization of perfusion techniques that allowed the verification of the hypothesis that were introduced into the theoretical model.
The experimentation involves technical problems, also because the placenta is the junction of two different but partially interdependent organisms, and each of them can influence its functioning.
Anyway, during the experimentation, several clinical variables can be easily controlled: this allows to neglect some of them, simplifying the starting hypothesis, and to analyse separately some other ones. Figure n.1 shows the variables involved for the mass exchange during the pregnancy.
However, the clinical application of the data previously obtained through the experimentation came across several problems: technical limitations and too heavy simplifications of the conditions leaded to results affected by a high level of uncertainty.
The lack of data in the scientific literature, both regarding the placental morphology and the physical, mechanical characteristics of the tissue, is an other encountered problem.
A contribution in this direction was the possibility to perform in vitro experimentation. It regards the study, the set-up and the verification of systems able to keep the placenta alive after the child-birth, to be able to perform a measurement of the morphological parameters simulating the presence of a physiologic fluidodynamical condition.
Then two techniques of placental perfusion (using bovine blood and formaline) will be described. The description regards both the instrumentation and the testing protocol, such that all the laboratory trials are reproducible.
The goals of these two series of experiments are different. The first one, with blood, is aimed at the study of the fluidodynamics of placental vessels, while the second one wants to "fix" the vessel structure to prepare it for a following morphometrical examination.
Afterwards a critical comparison between the obtained data and already available data is done, to realise and verify a model of circulation of the fetal placenta.
A model allows to define relationships among the involved variables. As the complexity of a biological system could hinder its detailed description, a model generally starts analysing only a part of it. Some partial models are introduced, then they are verified through experimental observations and eventually corrected, in order to be completed taking in consideration other variables, firstly not considered.
The possibility of foreseeing serious fetal pathologies from the variation of some variables is a need of the medical field. Sometimes a model can help the medical staff to express well-timed diagnosis before the child-birth.

This thesis is composed by four parts:
The first part briefly describes the placental physiology and some pathological conditions, and the diagnosis instruments.
The second part takes in examination the realized perfusion systems, dwelling on the testing protocol. Our experimentation has been carried out at the gynaecology and obstetrics ward of the San Paolo hospital, Milan, in collaboration with the medical staff.
The third part is dedicated to the analysis of a simulation model of the placenta.
To be clearer on problems that are not common to medicine and to engineering, we deemed it necessary to add a glossary in the fourth part, to explain the technical terms, with some conversion tables for units of measure currently used in medicine.

During the two years we spent since when the outline of this work was traced, we referred to a big number of people, often taking advantage of their patience, to get information, materials and favours.
Among them we should like to mention dott. Alessandra Pavesi, who followed the experimentation providing the essential link between the medical staff and us, and dott. Gaetano Bulfamante, the pathologist who performed the tests vouching for the validity of the experiments.
 
 
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Last updated: October 1, 2003