Increase In Placental Blood Flow Research Articles

Role of adrenergic receptor subtypes in the control of human placental blood vessels.

The use of beta2-Adrenergic Receptor (AR) agonists and the potential use of alpha1-AR blockers as tocolytics raise the question of how they influence placental circulation. The receptor profile was characterized via the amounts of the mRNA of alpha1-AR subtypes and beta2-ARs. The mRNAs were detected by reverse transcription-polymerase chain reaction. Electric field stimulation (EFS) was applied to test the pharmacological reactivity of the placental vessels. Expressions of beta2- and all subtypes of alpha1-AR mRNA were demonstrated in human placental vessels, and were significantly higher in the arteries. A significant difference was not found between the veins and the arteries as concerns the amount of alpha1D-AR mRNA. There was a preponderance of alpha1A- and alpha1B-AR mRNA as compared to alpha1D-AR mRNA both in the arteries and in the veins. beta2-AR agonists and alpha1-AR antagonists antagonized the EFS-induced contractions of the placental arteries in a dose-dependent manner. These effects were significantly less marked on veins at all applied doses. Urapidil antagonized the EFS-induced contractions of both the placental arterial and vein rings in a dose-dependent manner. The beta2-, alpha1A-, and alpha1B-AR are the important subtypes involved in the regulation of the contractility of the human term placental vessels. The possible increase in placental blood flow mediated by these ARs can even be beneficial during pregnancy. Accordingly, the use of beta2-AR agonists and the potential use of alpha1-blockers as tocolytics seem safe on the basis of in vitro examinations as concerns the placental circulation.

The Role of Endogenous Endothelin in the Regulation of Uteroplacental and Renal Blood Flow During Pregnancy in Conscious Rats

Advancing pregnancy is characterized by a ten-fold increase in uterine blood flow and a 50 per cent increase in renal blood flow. To evaluate the involvement of endogenous endothelin (ET) in these haemodynamic changes the effect of bosentan, an ETA/B receptor antagonist, on uteroplacental and renal blood flow was studied in awake pregnant Sprague–Dawley rats. Regional blood flows were measured using microsphere technique immediately prior to and 30 min after bosentan administration (20 mg/kg i.v.). Four groups of animals (term: 23 days) were included: bosentan was administered to ten rats at gestation day (GD) 19 and nine at GD 20–21. In addition, four rats at GD 19 and five animals at GD 20–21 received saline and served as control groups. Basal placental blood flow increased significantly from 19 days' gestation to 20–21 days. Basal myometrial blood flow did not change with gestational age. At gestation day 19 bosentan increased placental and myometrial blood flow significantly (80 per cent and 43 per cent, respectively, P<0.05). This effect was not observed at gestation days 20–21. Renal blood flow did not change in response to bosentan at GD 19 but decreased by 20 per cent at GD 20–21 ( P<0.01). In conclusion, in the awake pregnant rat there is a significant endogenous ET dependent vasoconstrictor tone in the uteroplacental vessels that diminishes towards term. We speculate that this change in responsiveness to endogenous ET contribute to the increase in placental blood flow in late gestation.

The extent of trophoblast invasion in the preplacental vasculature of the guinea-pig

Pregnancy-induced structural changes in spiral arteries seem to be a prerequisite for successful fetal outcome in humans. It is unknown whether these changes also occur in other preplacental vessels (radial and arcuate arteries) in normal pregnancies. Since the radial and arcuate arteries need to dilate in order to accommodate the increase in placental blood flow during pregnancy, it is expected that they are also invaded by trophoblast and respond with structural changes. The objective of the present study was to evaluate the extent of trophoblast invasion in the guinea-pig preplacental vasculature and its effect on the vascular structure of mesometrial, myometrial and arcade arteries. Under general anaesthesia the vascular system of non- ( n=4), mid- ( n=4) and late- ( n=8) pregnant guinea-pigs was fixed by immersion or perfusion. Cross-sections of immersion-fixed mesometrial and arcade arteries were stained with toluidine blue. Cross-sections of perfusion-fixed mesometrial, myometrial and arcade arteries were stained with haematoxylin-eosin, Elastica van Gieson staining and antibodies against α-smooth-muscle-actin (ASMA), cytokeratin and factor VIII, to detect vascular smooth muscle, trophoblastic, and endothelial cells, respectively. In addition, the external and internal vascular circumference of sections from perfusion-fixed tissue was determined. All cross-sections were evaluated by light microscopy. In the course of pregnancy, progressive endothelial swelling, disappearance of the elastic lamina interna and disarrangement of the tunica media were observed in the myometrial and throughout the mesometrial arteries up to the junction with the arcade arteries. These changes coincided the migration of keratin-positive staining giant cells. It is concluded that in normal guinea-pig pregnancy, structural changes occur in the entire mesometrial artery and at least a part of the myometrial artery, although such changes were not seen in the arcade artery.

Selective increase in placental blood flow by atrial natriuretic peptide in hypertensive rats

Effects of atrial natriuretic peptide on systemic, renal, uterine, and placental hemodynamics were determined in 16-day pregnant normotensive and hypertensive rats and in 20-day pregnant normotensive rats under pentobarbital anesthesia. Relative to 16-day pregnant normotensive rats, the total peripheral resistance was higher in 16-day pregnant hypertensive and 20-day pregnant normotensive rats; atrial natriuretic peptide significantly (p less than 0.05) decreased the total peripheral resistance in the latter two groups of animals. Atrial natriuretic peptide increased the placental blood flow in each of the three groups of animals without significantly affecting renal blood flow. This selective increase in placental blood flow normalized placental hemodynamics in hypertensive rats.

A longitudinal study of cardiac output in unstressed pregnant guinea pigs.

A previous study in pregnant guinea pigs failed to demonstrate any increase in cardiac output when a group of pregnant animals was compared with four nonpregnant animals. In the current study an increase in cardiac output of 35 +/- 14 (SE) ml/min, a 13% increase, was observed during an average 2-wk interval between 44 and 58 days of pregnancy (P less than 0.05, term 68 days, n = 8). A significant increase in placental blood flow of 14.8 +/- 6.2 ml/min (42% increase, P less than 0.05) was also observed during this interval without significant change in the percentage of cardiac output going to the uterus. The data on cardiac output and its distribution to the uteroplacental circulations are consistent with reports in other mammalian species; to accommodate the increased demands of the uteroplacental circulation, cardiac output increases as pregnancy advances. These data demonstrate that multiple observations in the same animal describe cardiac output and its distribution more accurately than a single observation.

Albumin Infusion Does not Alter the Intervillous Blood Flow in Severe Pre‐Eclampsia

Intervillous blood flow (IVBF) was measured by the 133Xe intravenous method before and after a 100 ml infusion of 20% human albumin in 13 cases of severe pre-eclampsia. In spite of the significant increase in serum albumin and colloid osmotic pressure values, no parallel direction of change in IVBF values could be seen to result from the immediate effects of volume expansion therapy. The results suggest that the use of albumin infusion is of no specific value in the treatment of severe pre-eclampsia in terms of evaluation at the level of placental circulation. The observation of an increase in placental blood flow in cases of real hypoalbuminemia calls for a further elucidation.

Uteroplacental blood flow during pregnancy in chronically catheterized guinea pigs.

Uterine blood flow and its distribution to uterus, placenta and subplacental structures was measured in 18 pregnant guinea pigs studied under chronic steady-state conditions. Maternal cardiac output averaged 266 +/- 14 ml/min. Placental blood flow (PBF) remained less than 4 ml/min until 50 days gestation, after which it increased rapidly, attaining flows of 16 ml/min at term. PBF also increased linearly with placental weight (r = 0.76, P less than 0.001); however, the increase in PBF with gestational age is evident even in narrow weight ranges, indicating hyperperfusion of term placentas relative to those earlier in gestation. Fetal weight correlated with measured placental blood flow supplying the corresponding placenta after 50 days gestation (r = 0.72, P less than 0.001).

1376 CIRCULATORY EFFECTS OF HYPERINSULINEMIA IN THE NEAR TERM OVINE FETUS

Ovine fetal hyperinsulinemia is associated with increased oxygen consumption, increased glucose uptake and decreased arterial O2 content. We used eight mixed breed ewes with 114-132 day singleton pregnancies to measure the magnitude and distribution of fetal cardiac output in order to define the causes of insulin-induced hypoxemia. During an uninfused control period and again after 12, 24 and 48 hours of exogenous insulin infusion (0.05U/kg/hr), we measured umbilical vein-artery whole blood concentrations of glucose and oxygen. We used the distribution of each of four microsphere injections to determine total cardiac output and organ blood flow. Insulin infusion was associated with increasing insulin concentration following a 12 hour lag period. We confirmed an increase in cardiac output (+19%, P<0.02) and a progressive fall in arterial O2 content (0.33mM to 0.23mM, P<.001). During insulin infusion, blood flow increased to the brain (+50%, P<0.05), adrenal (+56%, P<0.01), and carcass (+44%, P<0.02). Placental blood flow did not change during infusion and fell when expressed as a percentage of cardiac output (45% to 34%, P<.002). The hypoxemia during insulin infusion occurs as a result of increased O2 consumption without a corresponding increase in placental blood flow. If similar effects occur in humans, hyperinsulinemic hypoxia may account for the near term fetal and neonatal mortality among women with poorly controlled diabetes.

Indomethacin is a placental vasodilator in the dog. The effect of prostaglandin inhibition.

The effect of 8 mg/kg of indomethacin on uterine blood flow, prostaglandin production, and intraamniotic fluid pressure was examined in late pregnant dogs. Uterine blood flow was measured with 15 mum radiolabeled microspheres. Because we found that a significant percentage of the microspheres shunted through the placental circulation into the lungs, we calculated placental blood flow by adding the shunted microspheres through the placenta to the nonshunted microspheres in the placenta. Total uterine blood flow significantly increased from 271+/-69 ml/min during control period to 371+/-72 ml/min (P < 0.01) 30 min after indomethacin. This increase was attributable to the change in blood flow to the placental circulation (222+/-58 to 325+/-63 ml/min; P < 0.01). Associated with these hemodynamic changes we found an almost complete suppression of uterine prostaglandin E(2) production (1,654+/-305 to 51+/-25 pg/ml; P < 0.01) as measured by gas chromatography-mass spectrometry. In addition, we found that indomethacin treatment resulted in uterine relaxation as measured by intraamniotic fluid pressure changes (11.2+/-1.3 mm Hg to 8.5+/-1.2 mm Hg; P < 0.001). We conclude that indomethacin causes an increase in placental blood flow without any change in flow to the rest of the uterus, and that this dose of the drug inhibits greater than 95% of uterine prostaglandin production. In addition, indomethacin is responsible for uterine relaxation. The increase in placental blood flow after indomethacin is probably a result of uterine relaxation, which is secondary to prostaglandin synthesis inhibition.