Decrease In Uterine Blood Flow Research Articles

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

1. The effects of antagonism of the maternal renin-angiotensin system (RAS) with either an angiotensin II type 1-(AT1) specific receptor blocker (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) were compared in chronically-catheterised ewes and their foetuses during late gestation. 2. Daily from 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received i.v. either GR138950 (3 mg kg-1; n = 10), captopril (3 mg kg-1; n = 6) or an equivalent volume of vehicle solution (0.9% w/v saline; n = 10). 3. Within 2 h of drug administration, GR138950 abolished the maternal, but not the foetal, pressor responses to angiotensin II (AII; 100-188 ng kg-1, i.v.; P < 0.05), whereas captopril abolished both the maternal and foetal pressor responses to angiotensin I (AI; 400-750 ng kg-1, i.v.; P < 0.05). 4. On the first day of treatment, maternal blood pressure decreased in all GR138950-treated (-21 +/- 4 mmHg; P < 0.05) and captopril-treated (-13 +/- 5 mmHg; P > 0.05) ewes at 2 h after drug administration. Captopril also significantly decreased foetal blood pressure by 5 +/- 1 mmHg (P < 0.05). However, foetal blood pressure in the GR138950-treated animals remained unchanged. Maternal and foetal heart rates were unaffected by any treatment. Uterine blood flow was significantly reduced within 2 h of both GR138950 (-130 +/- 20 ml min-1; P < 0.05) and captopril (-72 +/- 16 ml min-1; P < 0.05) administration. 5. On the first day of treatment, maternal arterial haemoglobin (Hb) concentration and oxygen (O2) content increased at 2 h in all GR138950-treated and captopril-treated ewes. Foetal arterial pH and oxygenation (O2 content, O2 saturation and Pao2) were reduced by a similar extent in both groups of drug-treated ewes. 6. After one week of daily GR138950 administration, maternal blood pressure decreased from a pretreatment value of 96 +/- 5 mmHg on day 1 to 79 +/- 2 mmHg by day 7 (P < 0.05). Captopril treatment had no long-term effect on maternal blood pressure. Although foetal blood pressure increased by 3 +/- 1 mmHg over a week of vehicle treatment (P < 0.05), no significant differences were observed between the long-term changes in foetal blood pressure in all three groups of animals. 7. There were no long-term effects of drug administration on maternal Hb concentration or oxygenation, or on the foetal haematological parameters. However, changes in maternal PaCo2 observed in the GR138950-treated (+1.4 +/- 0.5 mmHg; P < 0.05) and captopril-treated (+3.3 +/- 1.1 mmHg; P > 0.05) ewes were significantly different from those seen in the vehicle-treated animals (P < 0.05). 8. There were no apparent adverse effects of maternal GR138950 or captopril treatment on foetal viability. 9. The present study demonstrated that administration of either GR138950 or captopril to pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a decrease in uterine blood flow. However, only captopril appeared to cross the placenta to influence directly the RAS of the sheep foetus. This suggests that the fall in foetal oxygenation observed after AT1-specific receptor blockade and ACE inhibition originates primarily from changes in the maternal and/or placental vasculature. Despite these changes, neither GR138950 nor captopril were detrimental to the outcome of pregnancy when foetal blood loss was kept to a minimum.

Sympathetic and parasympathetic regulation of the uterine blood flow and contraction in the rat

The effects of electrical stimulation of hypogastric sympathetic and pelvic parasympathetic nerves on uterine blood flow and contraction in anesthetized female non-pregnant normal cycling rats were examined. Electrical stimulation of the efferent pelvic nerve with supramaximal intensity induced marked increase of uterine blood flow accompanied by uterine contraction. On the other hand, the stimulation of efferent hypogastric nerve caused decrease of uterine blood flow accompanied by uterine contraction. These responses could only be elicited with stimulus intensity above the threshold for unmyelinated C fibers in both the hypogastric and pelvic nerves. Intravenous administration of atropine (0.5 mg/kg) totally blocked the response of uterine contraction elicited by pelvic and hypogastric nerve stimulation and also the increase of blood flow induced by pelvic nerve stimulation. Intravenous administration of phenoxybenzamine (0.5 mg/kg) blocked the decreased response of uterine blood flow induced by hypogastric nerve stimulation. It was concluded that uterine blood flow and contraction were regulated by both the parasympathetic and sympathetic nerves, but in different manners; blood flow is regulated reciprocally (1) by parasympathetic vasodilators mainly via activation of muscarinic cholinergic receptors, and (2) by sympathetic vasoconstrictors via activation of α-adrenergic receptors; contraction is produced by activation of both parasympathetic and sympathetic nerves via muscarinic cholinergic receptors.

The effects of xylazine on intrauterine pressure, uterine blood flow, maternal and fetal cardiovascular and pulmonary function in pregnant goats.

To investigate the effects of xylazine on pregnant goats, xylazine induced changes in heart rate (HR), arterial blood pressure (ABP) and arterial blood pH and gases in the mother and fetus, as well as changes in intrauterine pressure (IUP) and uterine blood flow (UBF), were studied using a chronic preparation model of pregnant goats. Intramuscular administration of xylazine (0.2 mg/kg b.w.) caused a marked decrease in HR and ABP of the mother, which remained significantly reduced up to 120 min. In the fetus, a significant decrease in HR and a significant increase in ABP were recorded after only 5 min. Significant decreases of maternal arterial blood pH and oxygen partial pressure (Po2) were observed up to 120 and 30 min after the injection, respectively. Fetal arterial blood pH and Po2 also decreased, but these changes were milder and less persistent than those of the mother. Within 2 to 5 min after the administration of xylazine, IUP began to increase and remained high for about 15 min. Thereafter, there was a frequent periodic increase in IUP. After 5 min, UBF decreased significantly and remained low up to 120 min. A fall in UBF was associated with a rise in IUP. These findings suggested that administration of xylazine to pregnant goats results in a decrease in UBF arising from the induction of uterine contractions, a decrease in circulating blood volume, hypoxemia and acidosis in the mother.

Uterine circulatory dysfunction induced by whole-body vibration and its endocrine pathogenesis in the pregnant rat.

Effects of whole-body vibration on normal pregnancy were studied in the rat. Uterine blood flow and five endocrine functions corticosterone (CS), estradiol (E2), progesterone (P), prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) concentration were measured in rats exposed to whole-body vibration with an acceleration of 10 m.s-2 at a frequency of 8 Hz. While no change in uterine blood flow was observed in control rats, uterine blood flow was significantly decreased 75 and 90 min after exposure to vibration. The uterine blood flow at 15 and 30 min was increased by pretreatment with intraperitoneal injections of angiotensin II (AII). In contrast, in AII pretreated rats exposed to the vibration, uterine blood flow was significantly reduced 90 min after exposure. The CS concentration was increased by vibration independently of the pretreatment with AII. Neither E2 nor PGF2 alpha concentration were changed by the vibration with or without AII administration. The P and PGE2 concentrations were both decreased by vibration in the absence of AII, while the decrease in PGE2 induced by the vibration was also found in AII-treated rats. The present results indicated that the pregnant rats subjected to whole-body vibration responded with changes in uterine and ovarian function. The observed decrease in uterine blood flow may have been the result of reduced PGE2 concentration resulting from an indirect effect of vibration.

Interference with uterine blood flow by clomiphene citrate in women with unexplained infertility

To investigate the effect of clomiphene citrate on the uterine blood flow in women with unexplained infertility. Twenty-one women who had normal uterine blood flow (pulsatility index [PI] less than 3 from the LH peak to the middle luteal phase of a natural ovulatory cycle) were enrolled in this study. Patients were given clomiphene citrate (100 mg/day) from days 5-9 of the next ovulatory cycle. The PI values measured in the natural and clomiphene citrate-treated cycles were compared using repeated measures analysis of variance. Their correlations with the estradiol (E2) and progesterone concentrations in the treatment cycle were calculated using the Pearson correlation coefficient. In the natural cycles of those with normal uterine blood flow, the highest impedance of uterine blood flow was detected at the late follicular phase, then blood flow increased during the luteal phase. In the clomiphene citrate-treated cycles, a statistically significant decrease in uterine blood flow also occurred during the early luteal phase (P < .05). No significant correlation of E2 or progesterone serum concentrations with PI values of the uterine artery could be found in either natural or clomiphene citrate-treated cycles. The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage.

Society for Obstetric Anesthesia and Perinatology

Society for Obstetric Anesthesia and Perinatology

Isolation and Characterization of Vasoactive Lipids from the Needles of Pinus ponderosa

Ingestion of ponderosa pine needles by late-pregnant cattle causes premature parturition induced by a profound and progressive decrease in uterine blood flow. In vitro perfused placentomes obtained from late-pregnant cows were used in the bioassay-guided fractionation of Pinus ponderosa pine needles to isolate a new class of vasoactive lipid substances. Chromatographically inseparable mixtures of active compounds were isolated by Soxhlet extraction and flash column chromatography. The structures of intact myristate and/or laurate diesters of 1,14-tetradecanediol or 1,12-dodecanediol in these extracts were determined by lH and 13C NMR, IR, and high- and low-resolution FAB mass spectrometric analyses. Saponification of small samples of isolated diesters, derivatization, and GCiMS verified major components as lauric and myristic acids and 1,14-tetradecanediol. Structures of individual components of mixtures of lipids were confirmed by MS-MS analysis.

Glutamate release from the ovine fetal brain during maternal hemorrhage. A study using chronic in utero cerebral microdialysis.

Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was < 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.

Systemic and uterine vascular response to serotonin in third trimester pregnant ewes

Released from aggregating platelets, serotonin (5HT) among other vasoactive components is considered to play an important role in preeclampsia, one of the most common medical complications of pregnancy. This study was designed to evaluate the simultaneous uterine and systemic vascular effects of systemically administered serotonin in pregnant sheep and compare them to the well known effects of angiotensin II and norepinephrine. Nine instrumented pregnant ewes received intravenous (inferior vena cava) infusions of increasing doses of serotonin, norepinephrine and angiotensin II in random order. Cardiac output, arterial blood pressure, heart rate, and uterine blood flow were recorded. Systemic administration of serotonin at doses of 2, 4, and 8 μg/kg body weight/min caused a slight increase in mean arterial blood pressure (1, 4 and 11%), a large decrease in uterine blood flow (10, 37, and 71%) but did not change cardiac output. Serotonin led to an increase in uterine vascular resistance with only small changes in systemic vascular resistance (UVR 17, 107, and 363% vs. SVR 3, 10 and 11%). In contrast, angiotensin II increased both systemic and uterine vascular resistance (SVR 16, 37, 56, and 95% and UVR 5, 16, 28 and 99%). Norepinephrine also raised both systemic and uterine vascular resistance, though to a different extent (SVR 5, 17, 37, and 118% vs. UVR 5, 46, 84 and 304%). Systemic infusions of serotonin in third trimester pregnant ewes resulted in uterine vasoconstriction. In contrast to the marked effect on the uterine vasculature, the systemic cardiovascular responses were small, thus demonstrating a nearly selective effect of serotonin on the uterine vasculature at the doses administered. Increased release and decreased metabolism of serotonin in preeclampsia therefore could lead to significant reductions in uteroplacental blood flow before hypertension occurs.

Effect of endothelin-1 on the uterine vasculature of the pregnant and estrogen-treated nonpregnant sheep

OBJECTIVE: This study was designed to evaluate the uterine vascular responses to endothelin-1 in pregnant and estrogen-treated nonpregnant sheep.STUDY DESIGN: Seven pregnant and five nonpregnant oophorectomized ewes received local uterine artery infusions of endothelin-1, norepinephrine, and phenylephrine. Arterial blood pressure, heart rate, and uterine blood flow were recorded.RESULTS: Endothelin-1 (0.01 to 3.0 µg/min), norepinephrine (0.1 to 3 µg/min), and phenylephrine (0.1 to 10 µg) produced significant dose-related decreases in uterine blood flow and increases in uterine vascular resistance. On a nanomoles infused per minute basis, endothelin-1 was much more potent than norepinephrine and phenylephrine as a uterine artery vasoconstrictor in both pregnant and nonpregnant sheep. The uterine vascular responses to norepinephrine and phenylephrine were similar in pregnant and nonpregnant ewes, whereas response to endothelin-1 was blunted in pregnancy.CONCLUSION: Endothelin-1 is an extremely potent uterine vasoconstrictor in both pregnant and nonpregnant ewes, but the uterine vascular responsiveness to endothelin-1 is decreased in pregnancy. (AM J OBSTET GYNECOL 1992;167:1642-50.)

Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis

Our study was designed to determine whether nitric oxide mediates estrogen-induced increases in uterine blood flow. Six nonpregnant oophorectomized ewes were instrumented with uterine artery flow probes and catheters. Ewes received estradiol-17 beta 1 microgram/kg, which maximally increased uterine blood flow by 120 minutes. Each animal then received local bolus injections of the nitric oxide synthetase inhibitor L-nitroarginine methyl ester. Estradiol-17 beta increased uterine blood flow from 16 +/- 6 to 139 +/- 32 ml/min by 120 minutes. Local uterine artery administration of L-nitroarginine methyl ester (1 to 30 mg) caused a dose-related decrease in uterine blood flow, which reached a maximum of 59% +/- 6% inhibition. Higher doses of L-nitroarginine methyl ester less than or equal to 10 mg/kg (330 to 460 mg) given locally led to a maximum inhibition of 79% +/- 3% but showed systemic responses. Estradiol-17 beta-induced increases in uterine blood flow are mediated mainly by nitric oxide; the observed vasodilation can be antagonized by the intraaterial administration of nitric oxide synthetase inhibitor L-nitroarginine methyl ester.

Hydralazine does not restore uterine blood flow during cocaine-induced hypertension in the pregnant ewe.

Cocaine abuse is widespread, and its use by the parturient has potential significant adverse effects in both the mother and the newborn. This study was undertaken in gravid ewes to determine the effects of treatment of cocaine-induced hypertension with hydralazine (Apresoline) on the maternal and fetal cardiovascular systems, catecholamine response, blood gas and acid-base status, and uterine blood flow (UBF). Twenty-one experiments were performed in 15 chronically instrumented ewes near term gestation. After a 30-min control period, cocaine was given intravenously to all ewes for 55 min to induce and maintain increased maternal mean arterial pressure (MMAP) and reduced UBF. The sheep were randomly assigned to receive either cocaine alone (n = 11, control group) or hydralazine (n = 10, treatment group), starting 15 min after the cocaine administration. Both drugs were discontinued 55 min after the start of the cocaine administration, followed by a 35-min recovery period. In the control group, cocaine administration resulted in a 31 +/- 13% (SD) increase in MMAP (P less than 0.05) and a 26 +/- 21% reduction in UBF (P less than 0.05). In the treatment group, the initial cocaine administration resulted in a similar increase in MMAP and decrease in UBF. Hydralazine therapy restored MMAP toward baseline after 20 min of administration, but UBF remained reduced (37 +/- 17%) throughout therapy (P less than 0.05) and recovery (18 +/- 13%) (P less than 0.05). The maternal heart rate increased maximally by 121 +/- 33% (P less than 0.05) after the administration of hydralazine, compared with a 14 +/- 21% increase (P less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Ropivacaine and Bupivacaine on Uterine Blood Flow in Pregnant Ewes

The effects of ropivacaine, a new amide local anesthetic, on uterine blood flow and fetal well-being were compared with those of bupivacaine in 10 chronically instrumented pregnant ewes. In random sequence, animals received two intravenous infusions of each drug. The low infusion rate regimens were chosen to result in clinically relevant maternal plasma concentrations of local anesthetics, whereas the more rapid rates of infusions were given to assess the safety of higher maternal drug concentrations. An epinephrine infusion was given to demonstrate the appropriateness of the animal model for the measurement of uterine blood flow. Maternal and fetal heart rates, arterial blood pressure, and the ewe's central venous pressure, intraamniotic pressure, and uterine blood flow were recorded continuously. Arterial blood samples were taken from mother and fetus at frequent intervals to determine acid-base status and local anesthetic concentrations. A total of 39 studies were performed. None of the infusions of either local anesthetic resulted in a significant decrease in uterine blood flow or deterioration in fetal condition. The mean maternal plasma concentrations at the end of infusions were as follows: ropivacaine low dose, 1.60 +/- 0.35 micrograms/mL; bupivacaine low dose, 1.55 +/- 0.15 micrograms/mL; ropivacaine high dose, 2.50 +/- 0.37 micrograms/mL; and bupivacaine high dose, 1.83 +/- 0.19 micrograms/mL. Epinephrine infusion resulted in a 25% decrease in uterine blood flow without adverse fetal effects. We conclude that neither ropivacaine nor bupivacaine, as administered in this study, led to any ill effects on uterine artery blood flow or fetal well-being.

The maternal and fetal effects of milrinone and dopamine in normotensive pregnant ewes

The safety of milrinone, administered during gestation, was evaluated in seven chronically instrumented pregnant ewes and their fetuses. Each of the following six intravenous regimens was administered in random order: milrinone, 75 micrograms.kg-1, over 1 minute, followed by 240-minute infusions of the drug at a rate of 1, 2, or 4 micrograms.kg-1.min-1; dopamine 5 or 10 micrograms.kg-1.min-1 over 60 minutes; or normal saline solution, 0.5 ml.min-1 for 240 minutes. Maternal and fetal acid-base parameters, heart rate, and blood pressure were monitored as were the ewe's venous and intraamniotic pressures and uterine blood flow. Milrinone concentrations determined in maternal arterial blood samples obtained during 1 and 2 micrograms.kg-1.min-1 infusions were found to be within the human therapeutic range. Bolus injection of milrinone, as well as the lowest drug infusion, resulted in no significant changes in uterine blood flow, whereas 2 micrograms.kg-1.min-1 milrinone infusion led to a 14% to 19% increase in uterine blood flow between 120 and 240 minutes. With the highest milrinone infusion, this increase was approximately 20%. In contrast, with both dopamine infusions, a dose-related decrease in uterine blood flow of 15% to 26% occurred between 15 and 60 minutes. No milrinone could be detected in any fetal plasma samples. Fetal arterial pH and blood gas tensions did not change during milrinone infusions. Dopamine 10 micrograms.kg-1.min-1 led to a progressive decrease in fetal arterial pH and an increase in PaCO2, which may have been related to similar changes in the ewe. It is concluded that milrinone has no adverse effects on uterine blood flow and fetal well-being when administered during ovine pregnancy.

Does Magnesium Sulfate Alter the Maternal Cardiovascular Response to Vasopressor Agents in Gravid Ewes?

Magnesium sulfate (MgSO4) attenuates the maternal compensatory response to hemorrhage in gravid ewes, perhaps by decreasing the response to endogenous vasopressors. The purpose of this study was to determine whether MgSO4 alters the cardiovascular response of gravid ewes to vasopressor agents. Sixteen gravid ewes underwent a series of experiments consisting of administration of two exogenous and two endogenous vasopressors, each with and without a concurrent MgSO4 infusion. Dose-response curves were constructed for phenylephrine (an alpha 1-adrenergic agonist), ST-91 (an alpha 2-adrenergic agonist), angiotensin II, and arginine vasopressin (AVP). MgSO4 significantly attenuated the increase in maternal mean arterial pressure and systemic vascular resistance and the decrease in cardiac output during ST-91 infusion but not during phenylephrine, angiotensin II, or AVP infusions. MgSO4 significantly attenuated the increase in uterine vascular resistance during phenylephrine, ST-91, and angiotensin II infusions and the decrease in uterine blood flow during phenylephrine and angiotensin II infusions. MgSO4 also appeared to attenuate the decrease in uterine blood flow during ST-91 infusion (P = 0.067). The present study suggests that MgSO4 antagonizes the effects of alpha 1-adrenergic agonists, alpha 2-adrenergic agonists, and angiotensin II on the uterine vasculature, thus providing a level of protection for the fetus in situations of maternal stress.

Maternal and fetal effects of the supine and pelvic tilt positions in late pregnancy

Material and fetal cardiovascular effects of position change were assessed in 20 women in late pregnancy. On changing from the left lateral to the supine position, there was a 45% reduction in leg blood flow, measured by strain gauge plethysmography. Arterial resistance, measured with Doppler ultrasound in the femoral, brachial and uterine arteries, remained unchanged, confirming the absence of compensatory vasoconstriction. There was no change in blood pressure (BP) in the leg, indicating no significant aortic compression, but a rise in maternal heart rate in the supine position suggested the presence of inferior vena cava (IVC) compression. Neither the left or the right pelvic-tilt position was associated with a significant change in leg blood flow or maternal heart rate compared to the supine position. A possible ‘sluice’ effect in the placental circulation was not confirmed, as fetal heart rate and umbilical Doppler resistance did not change in any position. In the absence of active vasoconstriction and significant aortic compression, IVC compression is the likely cause of the decrease in leg blood flow, and also of the previously demonstrated decrease in uterine blood flow. Leg BP and Doppler ultrasound measurements of uterine artery resistance may not be adequate measures of the effect of posture on uteroplacental perfusion.

The nature of the embryo-protective interaction of propyl gallate with hydroxyurea

Hydroxyurea (HU) is a swiftly acting cytotoxic teratogen and an inhibitor of DNA synthesis. Within 2 h of material treatment, HU causes necrosis in proliferating tissues of rabbit embryos on gestational day 12. Co-administration of the antioxidant propyl gallate (PG) delays the onset of necrosis until 6 h and ameliorates the teratogenic effects seen at term. Since HU also causes a rapid, profound decrease in uterine blood flow in pregnant rabbits, it is necessary to determine whether HU and PG interact within the pregnant female or within the embryo. In order to establish that the site of HU-PG interaction is embryonic, HU, PG, HU-PG, or vehicle was injected directly into implantation sites. When embryos were examined microscopically at 4 h, necrosis was observed only in the HU-treated embryos. indicating that the palliative interaction between HU and PG takes place within the embryo. To resolve whether the alleviation of HU-induced embryotoxicity was due to decreased HU levels within HU-PG embryos, HU concentrations were measured in embryos from HU- and HU-PG-treated maternal rabbits at 15 min to 8 h post injection. The HU levels of the two groups differed significantly only at 4 h. The rates of uptake during the linear phase (times from 15 min to 3 h) did not differ. When HU concentration was plotted versus time, measurements of the areas under the curve also did not differ. To determine whether PG alters the HU-induced inhibition of DNA synthesis, 3H-thymidine incorporation into embryonic DNA was assayed at 2 h after HU, HU-PG, or vehicle injections. Both HU and HU-PG treatments produced a 10-fold decrease in 3H-thymidine incorporation relative to controls. These data suggest that the amelioration of HU-induced embryotoxicity as reflected in the delayed onset of necrosis is due to an interaction between HU and PG within the embryo and that the interaction affects neither embryonic HU uptake nor the HU-induced inhibition of DNA synthesis. The results are consistent with the notion that the antioxidant properties of PG may be responsible for the decrease in HU-induced developmental toxicity.

Uterine vascular resistance during compression of the umbilical arterial and/or venous circulation in sheep

Total umbilical cord occlusion and selective occlusion of the umbilical arteries and veins is associated with changes in uterine blood flow. In the present study, the resistance to uterine blood flow during selective occlusions of the umbilical arteries and/or veins was analysed in five chronically instrumented pregnant sheep in the last third part of pregnancy. An occluding device which allows separate occlusion of umbilical veins and arteries was applied to the umbilical cord. Median uterine artery blood flow was measured using an electromagnetic flow meter. Maternal pressures were measured in a branch of the uterine artery and vein. Two occlusions of the umbilical veins and/or arteries with a duration of 30–60 s were performed in each animal. Selective occlusion of the umbilical arteries resulted in a small increase in uterine blood flow from 637 ± 79 ml/min during control toward 664 ± 77 ml/min at the end of occlusion (p < 0.05). Uterine perfusion pressure (uterine arterial pressure — uterine venous pressure) did not change. No changes were observed in calculated uterine vascular resistance (Poiseuille equation). Selective occlusion of the umbilical veins on the other hand caused a decrease in uterine blood flow from 617 ± 75 ml/min during control to 546 ± 69 ml/min at the end of occlusion (p < 0.001), and a return to control value at 1 min after occlusion. The uterine perfusion pressure increased from 40.1 ± 6.8 mmHg during control to 42.8 ± 7.0 mmHg at the end of occlusion (p < 0.01). Uterine vascular resistance increased from 0.074 ± 0.017 mmHg · ml −1 · min before occlusion to 0.089 ± 0.0020 mmHg · ml −1 · min at the end of occlusion (p < 0.05). Occlusion of both umbilical arteries and veins simultaneously resulted in a decrease in uterine blood flow from 630 ± 66 ml/min during control to 589 ± 66 ml/min at the end of occlusion. Uterine perfusion pressure and uterine vascular resistance did not change, however. It is concluded that short-lasting occlusions of the umbilical veins affect the vascular resistance to maternal uterine blood flow.

Aerobic exercise during pregnancy. Special considerations.

Alterations in maternal physiology during pregnancy affect the physiological respect to aerobic exercise. Maternal resting oxygen consumption (VO2) and cardiac output increase during pregnancy. Heart rate (HR) becomes progressively elevated through gestation, whereas stroke volume (SV) increases until the third trimester and then declines until term, probably because of diminished venous return. Plasma volume increases earlier and to a greater magnitude than red cell volume, resulting in the 'haemodilutional anaemia' of pregnancy and a decline in the oxygen-carrying capacity. Ventilation is greater during pregnancy because of elevated tidal volume and unchanged rate of breathing. The acute and chronic (training) responses to aerobic exercise during pregnancy have not been thoroughly investigated. Specifically, the effect of gestational age, maternal activity status, and type, duration and intensity of exercise on maternal cardiovascular response have only recently begun to be explored. During pregnancy cardiac output during submaximal exertion increases above values in non-pregnant women, except perhaps late in gestation. Both heart rate and stroke volume contribute to the elevated cardiac output. Changes in submaximal exercise VO2 during pregnancy are dependent on the mode of exercise. At the same workload, VO2 increases during weight-bearing exercise, but usually does not differ from postpartum values during weight-supported exercise. One study found no change in VO2max during pregnancy compared to postpartum values. Some recent evidence indicates that the cardiac output vs VO2 relationship for pregnant women is within the range of average values reported for non-pregnant individuals. Exercise arterial-venous oxygen difference is lower during pregnancy, suggesting that the higher cardiac output is distributed to non-exercising vascular beds. The data are limited but suggest that the perfusion of exercising muscle is unchanged during pregnancy and that the major haemodynamic change is an augmented cardiac output so that blood flow to the uterus and fetus is not compromised. Only one study has measured blood flow during exercise in pregnant women. The reported 25% decrease in uterine blood flow during supine cycle exercise in women late in gestation must be interpreted cautiously because the uterus may obstruct the vena cava in the supine position. Studies of exercising pregnant animals usually indicate a decreased uterine blood flow but an enhanced oxygen extraction; the lower blood flow may be limited to non-placental areas. The applicability of these results to humans is unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

Uterine blood flow during the development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice.

Uterine blood flow was assessed in mice by measuring organ uptake of intravenously injected [14C]butanol. In ovariectomized mice, injection of 100 ng oestradiol-17 beta increased blood flow 5-fold over that of untreated controls. The injection of oestradiol-17 beta in progesterone-treated mice also increased uterine blood flow at the time of maximal sensitivity to a decidual stimulus, but not 4 days later. Absolute values of blood flow increased during development of the decidual cell reaction in proportion to the increase in uterine weight, reaching maximal values 96 h after decidual induction. When progesterone injections were stopped 72 h after decidual induction, a rapid decrease in absolute and relative blood flow values preceded the decrease in uterine weight. This decrease in uterine blood flow occurred within 12 h of removing a subcutaneous implant containing progesterone. These results are consistent with the view that increased uterine blood flow during decidual development may be necessary to support the rapid increase in uterine weight at implantation and the subsequent decrease in both relative and absolute uterine blood flow on withdrawal of progesterone may promote decidual regression in the mouse.