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116 J. Itskovitz-Eldor, I. Thaler
duces overgrowth of caruncles (highly vascularized
areas of the uterine mucosa that become the sites of
implantation and the formation of placental cotyledons)
[44] and growth of uterine blood vessels [45].
Its role in regulating uterine blood flow is controversial
[46].
The uteroplacental vasculature is sensitive to the
constrictive effect of catecholamines. Systemic infusion
of suppressor doses of norepinephrine has been
shown to reduce placental perfusion in the absence of
significant changes in arterial pressure [47]. It is also
sensitive to other endogenous vasoactive substances
(e.g., angiotensin II, prostanoids), which have the potential
to either increase or decrease uterine blood
flow by acting directly on the blood vessels or indirectly
by modifying the intrauterine pressure.
Changes in partial pressures of oxygen and carbon
dioxide have little direct effect on the uteroplacental
circulation. However, severe disruption of oxygenation
and acid-base balance (and maternal stress in
general) may increase uterine vascular resistance secondary
to the constrictive effect of catecholamines released
into the circulation and activation of the sympathetic
vasomotor nerves [30].
Pressure-Flow Relations
Data from animal experiments in which the pressureflow
relations in the uterine circulation were examined
have demonstrated a negative correlation between
amniotic pressure and uterine blood flow [48]
and a linear relation between flow and perfusion
pressure [20, 35, 49, 50]. In rhesus monkeys confined
to restraining chairs, the highest blood flows tended
to occur during the period of darkness when arterial
and intraamniotic fluid pressures were low [48].
These observations suggest that the uteroplacental
circulation is pressure-passive, is fully dilated, and
has no tendency toward autoregulation. Meschia [30]
compared the placenta and its venous outlets to a collapsible
tube (Starling resistor) [51] contained within
a cavity in which the pressure can increase above atmospheric
pressure in this system, and flow through
the placental bed depends on arterial perfusion pressure,
the external pressure exerted by the amniotic
fluid, and the pressure in the uterine venous outlet.
Although these relations have been demonstrated experimentally,
disparities were observed in the chronology
and amplitude of the 24-h periodic functions
for arterial blood pressure, intraamniotic pressure,
and uterine blood flow recorded continuously in rhesus
monkeys, indicating that uteroplacental perfusion
is modulated by factors in addition to those imposed
by pressure-flow relations [52].
The high basal rate of uterine perfusion provides a
margin of safety for the fetus because the uteroplacental
vasculature does not dilate in response to maternal
hypotension or hypoxia but is sensitive to the
constrictive effect of catecholamines. In the sheep,
oxygen supply to the fetus is approximately twice the
level necessary to maintain adequate fetal oxygen uptake
and normal oxidative metabolism. Fetal oxidative
metabolism can be sustained despite reductions in
uterine blood flow of about 50% [53±55]. However,
long-term reductions of even small magnitude have
cumulative metabolic effects that ultimately affect fetal
growth. It has been clearly demonstrated that fetal
growth is directly related to the normal incremental
increases in uterine blood flow throughout pregnancy
[21]. When reduced uterine flow is prolonged, fetal
and placental growth are slowed [21, 56]. Under these
circumstances uterine blood flow per unit weight of
the fetus and placenta may remain constant and does
not significantly differ from that of normally growing
fetuses [57, 58].
Fetal Circulation
During fetal life oxygenation is carried out in the placenta.
A large gradient of oxygen partial pressure
(PO 2 ), of about 60 mmHg, has been found between
maternal arterial blood and fetal umbilical venous
blood. The admixture of the oxygenated umbilical venous
blood from the placenta and systemic venous
blood from the fetal body further reduces the PO 2 of
blood distributed to the fetal body. The PO 2 of arterial
blood is 20±30 mmHg (considerably lower than the
adult value of close to 100 mmHg); it is somewhat
higher in the blood distributed to the brain and the
upper body from the ascending aorta than in blood
distributed from the descending aorta to the lower
body and the placenta. Despite the existence of a low
arterial concentration of oxygen, the fetus has adequate
oxygen delivery because, similar to the adult, it
does not extract more than one third of delivered
oxygen [59].
The presence of ductus arteriosus, the large communication
between the pulmonary trunk and the
aorta (Fig. 9.2), accounts for the almost identical
pressures in the aorta and the pulmonary artery in
the fetus. Similarly, because of the presence of the
foramen ovale, atrial pressures are almost identical,
and so the right and left ventricles are subjected to
the same filling pressure. Hence, unlike those in the
adult, fetal cardiac ventricles work in parallel rather
than in series. The output of the left ventricle is directed
through the ascending aorta to upper body organs,
thus preferentially perfusing the brain, whereas
the right ventricle mainly perfuses the lower body
and placenta through ductus arteriosus and the descending
aorta.