Study and Validation of a Model
of Fetoplacental Circulation
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