Increase In Uterine Blood Flow Research Articles

Estrogen associated changes in uterine blood flow and maternal recognition of pregnancy in Chinese (Meishan) pigs

Our laboratory has recently demonstrated a reduced embryonic growth rate and estradiol-17β (E 2β) content of preimplantation Meishan embryos compared with embryos of European breeds. Estrogen secretion by the preimplantation conceptus has been linked to both the transient increase in uterine blood flow (UBF), and maternal recognition of pregnancy (MRP) on Days 11–13 of gestation in European swine breeds. The objective of these experiments was to evaluate the temporal association between estrogen secretion by the preimplantation conceptus, increases in UBF and the onset of MRP in Meishan pigs. In Experiment 1, multiparous Meishan sows ( N = 3) were observed for estrus once daily, and hand-mated at first observed estrus (Day 0) and 24 h later with a Meishan boar. On Day 2 postmating, sows were bilaterally instrumented with blood flow transducers and uterine venous catheters. UBF (ml min −1) was monitored and blood samples collected once daily from Days 6 to 30 postmating. UBF increased on Day 11 ( P = 0.06) to peak on Day 13, then decreased on Days 14–17, before increasing progressively thereafter, coincident with increasing uterine E 2β secretion. In Experiment 2, second cycle Meishan ( N = 20) and Yorkshire ( N = 18) gilts were hand-mated at first observed estrus (Day 0), and 24 h later, to boars of their own breed. Embryos were flushed from the gilts on Day 9, 11, 13 or 15 postmating. Gilts were again observed for estrus to determine treatment estrous cycle length (ECL). Treatment ECL was similar ( P > 0.1) to presurgical ECL when embryos were collected from either Meishan or Yorkshire gilts on Days 9 and 11. ECL was extended in both breeds ( P < 0.05) when embryos were recovered on Days 13 and 15.

Effect of hyperthermia on uterine and umbilical blood flows in pregnant sheep

Uterine and umbilical blood flows were measured in pregnant sheep (125-142 days gestation) under normothermic and hyperthermic conditions using the Fick principle with [14C]antipyrine as the indicator. Exposure of the sheep to an ambient temperature of 43 +/- 1 degrees C (25-30% relative humidity) for 8 h increased maternal and fetal core temperatures 1.19 +/- 0.15 and 1.39 +/- 0.12 degrees C respectively. Maternal hyperventilation caused a significant decrease of both maternal and fetal arterial partial pressure of CO2 (Pa,CO2) and increase of arterial pH. Uterine blood flow increased significantly during the hyperthermia (+54.2 +/- 14.1%), the increase being correlated with the magnitude of the decrease of maternal Pa,CO2 (r = -0.84, P < 0.05) but not with the increase of maternal core temperature. The increase of uterine blood flow was not associated with a concomitant increase in the placental clearance of [14C]antipyrine, a result which could arise if the increase of blood flow was non-placental (i.e. did not occur within the cotyledons), or occurred through uterine arteriovenous shunts during the period of heat stress. Hyperthermia was not associated with a significant change of umbilical blood flow, placental transfer of glucose, or fetal glucose uptake. Since the loss of heat from the fetus occurs mainly across the placenta, we speculate that the apparent increase of uterine blood flow during maternal hyperthermia has an adaptive significance by maintaining conductive heat flux in a fetomaternal direction, even though cotyledonary (placental) blood flows did not increase.

Is uterine blood flow controlled locally or systemically in the pregnant rabbit?

We tested the hypothesis that uterine blood flow is regulated by systemic circulating factors. The alternative hypothesis is that uterine blood flow is regulated by local factors. Adult female New Zealand White rabbits were subjected to a unilateral tubal ligation and thereafter allowed to become pregnant (n = 9). A group of nonpregnant one-tube-ligated animals served as controls (n = 8). On day 21 of gestation uterine blood flow in the pregnant and nonpregnant uterine horns were measured with 15 microns microspheres. The concentration of prostaglandin E2 metabolites were measured in blood from the uterine veins and from the arterial circulation. Absolute uterine blood flow in the pregnant uterine horn was 12.9 +/- 4.7 versus 5.2 +/- 1.4 ml in the nonpregnant horn (p < 0.05). However, when expressed by blood flow per gram of tissue they were not different (p > 0.1). The uterine blood flow for the nonpregnant uterine horn in the pregnant animals was the same as that of the horns from nonpregnant animals. The level of prostaglandin E metabolites was greater in the uterine vein draining the pregnant horn compared to the nonpregnant horn (p < 0.05). These data support the conclusion that the increase in uterine blood flow observed during pregnancy is controlled largely by local factors induced by pregnancy.

Uteroplacental blood flow at rest and during exercise in late-gestation conscious rats.

The present studies were conducted to achieve three specific aims. First, techniques and procedures were developed to allow tissue and organ blood flow measurements by radioactive microsphere methodology in the conscious female rat. Second, technical aspects of the methodology were evaluated with emphasis on potential uteroplacental shunting of microspheres in the late-gestational period. Third, the above techniques and procedures were utilized to assess uteroplacental blood flow at rest and during exercise in conscious pregnant rats during the late stages of gestation, i.e., days 15, 19, and 22 of pregnancy. Results established the validity of tracer blood flow technical assumptions, and no significant increase in arteriovenous shunting of 15-microns microspheres either as pregnancy progressed or during superimposed exercise in near-term pregnant animals was detected. During the stages of pregnancy studied, cardiac output was enhanced approximately 20% near term. Marked and progressive increases in uterine blood flow were noted both in milliliters per minute and as percentage of cardiac output. Preferential placental perfusion during late-stage gestation was indicated by increased tissue flow (7 +/- 1, 84 +/- 12, 232 +/- 32 ml.min-1 x 100 g-1), increased percent cardiac output (1.7 +/- 0.1, 5.1 +/- 0.7, 11.0 +/- 1.7% cardiac output), and increased percent uterine blood flow (10 +/- 1, 59 +/- 3, 87 +/- 2% uterine flow) at days 15, 19, and 22 of gestation, respectively. Progressive maternal body weight increase during gestation enhanced exercise work intensity, as shown by heart rate and cardiac output at the end of 30 min of treadmill running at 8.5 m/min, 0% incline.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effect of calcitonin gene-related peptide on the uterine vasculature of the nonpregnant ewe

The current study was designed to evaluate the uterine vascular effects of calcitonin gene-related peptide on the uterine vasculature of nonpregnant sheep and compare them with the effects of prostacyclin. Five nonpregnant oophorectomized ewes were instrumented with uterine and pulmonary artery flow probes and catheters. Dose-response curves were constructed according to increasing doses of calcitonin gene-related peptide (0.01, 0.03, 0.1, 0.3, 1, and 3, micrograms/min) and prostacyclin (0.03, 0.1, 0.3, 1, 3, and 10 micrograms/min) via 10-minute uterine artery infusions. Both calcitonin gene-related peptide and prostacyclin produced a significant increase in uterine blood flow and a decrease in uterine vascular resistance. Calcitonin gene-related peptide was found to be approximately 17 times more potent than prostacyclin as a vasodilator. Local uterine artery infusions of calcitonin gene-related peptide led to significant increases in heart rate but did not alter blood pressure, cardiac output, or total peripheral resistance at the doses tested. In contrast, at doses of prostacyclin that produced similar uterine vasodilatation, prostacyclin led to significant decreases in systemic arterial blood pressure and total peripheral resistance and increases in heart rate and cardiac output. These data strongly suggest that calcitonin gene-related peptide, an endogenously occurring vasoactive peptide, could play an important role in regulating uterine and systemic hemodynamics.

Role of polyamines in regulation of uterine blood flow of ovariectomized rats

Polyamines have been shown to relax several types of smooth muscle including vasculature. In the estrogen-treated uterus, uterine blood flow and polyamine levels in the uterus are increased. The relaxant effect of polyamines on blood vessels suggest that polyamines may act on uterine vasculature to cause uterine hyperemia. In this study, we examined the roles of polyamines in regulating uterine blood flow. Ovariectomized rats were administered with polyamines or estrogen. The uterine blood flow was then measured by employing radioactive microspheres. The direct injection of polyamines into systemic circulation caused a 3-fold increase in uterine blood flow within 30 seconds. The polyamine-induced uterine hyperemia was counteracted by increasing extracellular calcium concentration. When rats were treated with estradiol, uterine blood flow increased. However, the treatment with α-difluromethylornithine, a polyamine synthesis inhibitor, did not attenuate the estrogen-induced uterine blood flow. Our results suggest that polyamines may affect uterine blood flow via antagonizing the entry of extracellular calcium. However, the detailed mechanisms via which polyamines involved in estrogenic stimulation of uterine hyperemia may require further studies.

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.

42 Endothelium-Derived Relaxing Factor Mediates Estrogen-Induced Increases in Uterine Blood Flow

42 Endothelium-Derived Relaxing Factor Mediates Estrogen-Induced Increases in Uterine Blood Flow

Magnesium sulfate and promethazine do not interact to cause hypotension in gravid ewes

The purpose of this study was to determine whether magnesium sulfate and promethazine interact to cause hypotension in gravid ewes. Fifteen experiments were performed in five chronicaly instrumented animals between 125 and 130 days of timed gestation (term = 145 days). In one group of experiments each animal received magnesium sulfate (4 gm intravenous bolus followed by 4 gm/hr intravenous infusion) then promethazine (50 mg intravenously). In a second group each animal received magnesium sulfate then saline solution as a control. In a third group each animal received saline solution then promethazine. Infusion of magnesium sulfate increased the mean ( ± SEM) serum magnesium concentration to 5.7 ± 0.6 and 6.6 ± 0.6 mg/dl in the magnesium sulfate-promethazine and magnesium sulfate—saline solution groups, respectively. Magnesium sulfate slightly decreased maternal mean arterial pressure (p < 0.05) and increased cardiac output (p < 0.05) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups. Otherwise there were no significant changes in maternal mean arterial pressure or cardiac output in any group. Promethazine increased maternal heart rate (p = 0.0001) in both the magnesium sulfate-promethazine and saline solution-promethazine groups. Magnesium sulfate increased uterine blood flow (p < 0.01) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups, but promethazine blunted the increase in uterine blood flow associated with magnesium sulfate. Similarly, magnesium sulfate decreased uterine vascular resistance (p < 0.01) in both the magnesium sulfate-promethazine and magnesium sulfate-saline solution groups, but promethazine eliminated the decrease in uterine vascular resistance associated with magnesium sulfate. Maternal and fetal arterial blood gas and acid-base values did not change in any group, except that there was a small, near-significant decrease (p = 0.06) in fetal pH 10 minutes after promethazine was given in the magnesium sulfate-promethazine group. We conclude that magnesium sulfate and promethazine did not interact to cause maternal hypotension in normovolemic gravid ewes. However, promethazine increased maternal heart rate and blunted the increase in uterine blood flow associated with magnesium sulfate.

Uteroplacental production of eicosanoids in ovine pregnancy

Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systematic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF 1α) in nonpregnant (n=4) and pregnant (n=8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE 2, PGF 2α, PGFM, 6-keto-PGFP 1α, and YxB 2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p<0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316±19 and 245±37 pg/ml), while levels of PGFM and PGI 2 metabolites 6-keto-PGF 1α were elevated 23-fold (31±14 to 708±244 pg/ml) and 14-fold (12±4 to 163±78 pg/ml), respectively (p<0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE 2 (397±36 and 293±22 pg/ml) and 6-keto-PGF 1α (269±32 and 204±32 pg/ml), p<0.05, but not PGF 2α or TxB 2. Although PGFM concentrations appeared to be greater in uterine venous (1197±225 pg/ml) as compared to uterine arterial (738±150 pg/ml) plasma, this did not reach significance (0.05<p<0.1). In normal ovine pregnancy arterial levels of PGI 2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE 2 and metabolize PGF 2α.

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.

Blood flow velocity waveforms in large maternal and uterine vessels throughout pregnancy and postpartum: a longitudinal study using Duplex sonography.

Blood flow velocity waveforms in large maternal and uterine vessels were measured longitudinally from 16 weeks gestation onwards until 12 weeks postpartum in 21 singleton pregnancies by duplex sonography. In the maternal carotid artery, time average mean velocity (TAVmean) did not show significant changes. In both the femoral artery and vein, however, significant changes were observed. In the femoral artery, TAVmean and systolic maximum velocities decreased with advancing gestation. In the femoral vein, TAVmean remained constant throughout pregnancy and was lower than postpartum. The resistance index in the uterine arteries decreased with advancing gestation and increased after delivery. Among many factors contributing to femoral arterial blood flow velocity changes in pregnancy, we suggest that a major one is the increase in uterine blood flow. Reduction in venous femoral blood flow velocity and increase in the femoral vein diameter might be associated with the common occurrence of venous disorders in pregnancy.

Structural and mechanical changes of uterine arteries during pregnancy in the pig.

A dramatic 15-fold increase in uterine blood flow in pigs occurs during pregnancy in association with marked increases in uterine arterial (UA) diameter. This study was conducted to determine UA collagen and elastin content, diameter, alpha 1- and alpha 2-adrenergic receptor (AR) numbers, norepinephrine (NE) and in vitro reactivity to phenylephrine on d 0, 20, 50, 80 and 110 of pregnancy in the pig. Uterine arterial collagen content declined progressively throughout pregnancy (P less than .01), whereas the content of elastin remained constant from d 0 to d 80, then increased (P less than .05) from d 80 to d 110. The UA collagen to elastin ratio was correlated with UA diameter (r = -.69; P less than .01), which increased from 4.5 mm on d 0 to 9.0 mm on d 110. Uterine arterial alpha 1-AR numbers remained low and constant throughout pregnancy, consistent with its retained ability to contract in response to phenylephrine. Uterine arterial NE content declined (P less than .05) from d 20 to d 80 before increasing slightly to d 110. Uterine arterial alpha 2-AR numbers remained high from d 0 to d 80 before decreasing (P less than .05) to low values on d 110. These data are consistent with a reduced adrenergic neuronal control and increased elasticity of the UA during pregnancy in the pig.

Distribution of adrenergic receptors does not explain regional differences in blood flow in the pregnant rabbit uterus

The increase in uterine blood flow during pregnancy is maximal at the placental implantation site, but the mechanisms of this increase are poorly understood. Adrenergic receptor activation may influence blood flow both directly and indirectly. We therefore asked whether distribution of myometrial adrenergic receptors within the rabbit uterus could explain the increased blood flow to smooth muscle under the placenta. α-Adrenergic and β-adrenergic receptor concentrations and affinities were measured in myometrium from under the placenta and compared to myometrium between placentas and distant from the placentas. There were no differences in receptor concentrations or affinities in different parts of the uterus. We therefore conclude that the distribution of adrenergic receptors in the pregnant rabbit uterus cannot explain the preferential blood flow to myometrium at the placental implantation site.

The effect of a leukotriene receptor antagonist, FPL 55712, on estrogen-induced uterine hyperemia in the nonpregnant rabbit

Estrogen results in delayed uterine hyperemia. We postulate that the leukotrienes may be the mediators of the uterine vascular responses to estrogen. To test this hypothesis, we gave FPL 55712, a selective leukotriene antagonist, to estrogen-primed, nonpregnant rabbits and measured regional blood flows by the radioactive microsphere technique. In 10 chronically catheterized animals, blood flows were measured in the control condition (C), and again 2 hours after systemic administration of estradiol (EST). Thirty minutes before administration of estradiol, five animals received systemic FPL 55712, whereas five animals received vehicle only. The vehicle group showed the expected increase in uterine blood flow from 0.62 ± 0.1 to 2.72 ± 0.4 ml · min−1 · gm−1, and decrease in uterine resistance from 144 ± 31 to 34 ± 8 peripheral resistance units (PRU) · gm, with a resistance ratio (estradiol/C) of 0.23 ± 0.01. Unexpectedly, the FPL 55712 group showed a further increase in uterine blood flow from 0.66 ± 0.1 to 4.60 ± 0.3 ml · min−1 · gm−1, and a decrease in resistance from 133 ± 25 to 17 ± 1 PRU · gm, with a resistance ratio of 0.13 ± 0.02. The leukotriene antagonist FPL 55712 potentiates estrogen-induced uterine hyperemia by 77% (P < 0.001). These data suggest that leukotrienes do not mediate, but rather inhibit, the uterine vascular responses to estrogen.

Uterine Blood Flow during Early Pregnancy in Ewes: Interaction between the Conceptus and the Ovary Bearing the Corpus Luteum

To determine if a transient increase in uterine blood flow (BF) and estradiol-17 beta (E2 beta) secretion occurs during maternal recognition of pregnancy in ewes (as previously observed for sows and cows), 40 nonpregnant (NP) ewes were assigned in equal numbers to surgery on d 9, 11, 13 or 15 postestrus (d 0 = day of estrus). For 20 NP ewes (five/day), each uterine horn (UH) was flushed with saline and uterine flushings (UF) collected. For the remaining 20 ewes, BF was determined for each UH using electromagnetic transducers, and samples of uterine arterial (UA) and uterine venous (UV) blood were obtained from each UH. After an intervening cycle, each ewe was mated, subjected to surgery on the same day postmating as during her previous nonmated cycle, and BF measurements and UA and UV samples were obtained. In addition, each UH of pregnant (P) ewes was flushed and the location of conceptuses was determined. Concentrations of E2 beta and progesterone (P4) in UA and E2 beta in UV and UF were determined by radioimmunoassay. For NP ewes, BF (ml/min) was not different for UH ipsilateral or contralateral to the ovary bearing the corpus luteum (CL), and did not differ across days, averaging 6.5 +/- .4. For P ewes, BF to UH contralateral to the ovary bearing the CL on all days and BF to UH ipsilateral to ovaries bearing CL on d 9 was similar to BF of either UH of NP ewes, averaging 6.8 +/- .6. On d 11, 13 and 15 of pregnancy, BF to UH ipsilateral to the ovary bearing CL was elevated (P less than .01) twofold (13.3 +/- .9).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine Modulation of Uterine Blood Flow in Pregnancy

Uterine blood flow increases 15- to 20-fold during pregnancy. The fact that pregnancy is also characterized by dramatic increases in the production rate and plasma concentrations of estrogenic and progestational sex steroids has prompted investigators to explore a cause and effect relationship between these endocrine and physiologic changes. This article reviews the evidence that pregnancy-related increases in uterine blood flow are, at least in part, sex-steroid induced.

Use of magnesium sulfate as an anticonvulsant in severe pregnancy toxemia and eclampsia

Animal experimental studies conducted at the turn of the century resulted in the use of magnesium sulphate as an anticonvulsant in humans. In U.S. clinics, parenteral administration of magnesium sulphate became a routine procedure in the treatment of eclampsia and pre-eclampsia. This treatment has proved very effective in treating convulsions in pregnancy provided an adequate dosage was given amounting to up to 60 g daily. Mother and infant mortality were largely eliminated. Numerous clinical studies showed a negligible side effect rate. Side effects in the foetus: These are due to penetration of magnesium into the foetal blood circulation. Reports on an inhibition of cardiac rate fluctuation and changes in calcium levels have been contradictory, and hence not generally accepted. It is claimed that the parathormone level may drop slightly. Isolated reports on foetal magnesium intoxications associated with depression of breathing, slackness and hyporeflexia often prompt the conclusion that this disease pattern had been due to immaturity and asphyxia. Generally, foetal magnesium blood levels do not correlate well with signs of magnesium intoxication. Urine excretion is greatly slowed down in foetal immaturity. Side effects in the mother: Short-term relaxing action on the uterus has been described frequently. High dosages have been successfully used in arresting labour if there is a tendency to premature birth. Increase in uterine blood flow was seen after administration of magnesium sulphate in animal experiments. Magnesium is said to reduce blood coagulation by influencing fibrinolysis and thrombocyte resistance. However, a somewhat enhanced loss of blood during birth is said to be more likely due to relaxation of the uterus than to a disturbance of blood coagulation. Rapid intravenous injection causes short-term flushing, nausea and vomiting. Short-acting drops in blood pressure are possible. The cardiac output is said to increase at the conventional dosage level whereas the peripheral resistance drops due to vasodilation. Increases and decreases in heart rate have been reported, but in most cases no changes were seen. Changes in ventricular action time occur with toxic doses only, which can lead to cardiac arrest in the diastole. Other toxic signs are hyporeflexia, depressed breathing and CNS depressions which may result in coma. Hyporeflexia always occurs before the other toxic signs appear, so that it can be used as a clinical control criterion. Calcium gluconate, given via the IV route, is a good and rapid-acting antidote.(ABSTRACT TRUNCATED AT 400 WORDS)

Uterine and systemic vascular responses to dopamine in pregnant ewes.

The systemic and uterine hemodynamic effects of dopamine were studied in six near-term pregnant Texel sheep. Dopamine was administered by i.v. infusion in doses ranging from 2 to 16 micrograms per kilogram per minute. After administration of 2 and 4 micrograms/kg/min, Dopamine produced a statistically significant increase in uterine blood flow (p less than 0.02). The mean value of the increase was 68.3 ml/min. When doses of 8 and 16 micrograms/kg/min were given, the responses were variable. Systolic and diastolic arterial pressure remained unchanged up to dopamine dosages of 8 micrograms/kg/min. Heart rate also showed no significant increase but a trend in this direction was seen. Low-dosages of dopamine could be used in the treatment of patients with placental insufficiency.