Critical tricuspid insufficiency due to papillary muscle rupture. A result of prenatal hypoxic insult.

Fatal tricuspid insufficiency secondary to papillary muscle rupture due to prenatal hypoxic insult occurred in a full-term newborn. The diagnosis of flail tricuspid valve should be considered when fetal distress is encountered in a newborn with persistent hypoxemia. Prenatal diagnosis of this condition combined with prompt delivery, prostaglandin E1 therapy, and possible surgical repair of the tricuspid valve may improve chances of survival.

Antepartum predictors of fetal distress in postterm pregnancy.

The purpose of this study was to determine the efficacy of combining nonstress testing with ultrasound assessment of amniotic fluid volume for the antenatal evaluation of the postterm fetus. Postterm patients (884) were managed with amniotic fluid assessments and nonstress tests (including evaluation for variable and late decelerations) twice a week. There were no perinatal deaths or major neonatal morbidity. However, the antenatal testing sensitivity, specificity, negative, or positive predictive values were not improved by combining the two tests. Individually, amniotic fluid assessment was just as accurate a predictor of fetal well-being and was a significantly more sensitive test than the nonstress test. In addition, antenatal predictors of fetal distress and intrapartum signs of fetal distress were almost exclusively those reflective of umbilical cord compromise. These findings stress the importance of antenatal screening for signs of umbilical cord compromise as an early indication of potential fetal compromise. Although the results also suggest that amniotic fluid assessment is superior to the nonstress test, they do not conclusively support the use of amniotic fluid assessment as the sole parameter for postterm antenatal surveillance.

The role of antepartum testing in the management of postterm pregnancies with heavy meconium in early labor.

The documented association between heavy meconium in early labor and increased perinatal morbidity and mortality has alerted physicians to the presence of a potential high-risk fetal condition and to the possible need for immediate fetal blood pH determination. The purpose of this study was to determine whether antepartum fetal assessment can predict whether a postterm fetus with heavy meconium in early labor is at low or high risk for an adverse perinatal outcome. Eight hundred thirty-nine postterm patients were followed with antepartum testing, consisting of twice-weekly fetal heart rate (FHR) testing and ultrasonic amniotic fluid volume estimation. Overall, patients with heavy meconium in early labor had a significantly greater frequency of fetal distress. However, when women with heavy meconium in early labor were separated according to their antepartum testing results, those with normal results were found to have no greater risk for fetal distress or perinatal morbidity than women with normal testing and subsequently clear amniotic fluid. These findings suggest that postterm patients with heavy meconium in early labor and normal antepartum testing can be managed in labor in the same manner as low-risk patients without meconium.

Cortisol facilitates ovine fetal/maternal water transfer.

After the infusion of 500 ml 20% mannitol to 12 pregnant ewes, we studied fetal plasma osmolality responses in chronically catheterized fetal lambs at 129-140 days' gestation. To compare the effects of arginine vasotocin (AVT) alone and AVT plus cortisol on fetal/maternal water transfer, the mannitol infusion was repeated during a 2-h fetal infusion of AVT alone (7 microU/kg/min) and during infusion of AVT with cortisol (50 micrograms/h) (eight and six animals, respectively). The fetal osmolar response to maternal mannitol administration was compared to the response following the baseline mannitol study in the same sheep. In four of the ewes, an identical (sham) study was performed substituting 500 ml normal saline for the mannitol infusion to the ewe. Fetal AVT infusion significantly obtunded the fetal osmolality increment induced by maternal mannitol alone [P less than 0.001, analysis of variance (ANOVA)]. Fetal AVT administered concurrently with cortisol produced an increment in fetal plasma osmolality in response to maternal mannitol that was significantly enhanced compared with that during fetal AVT infusion alone (P less than 0.001, ANOVA). The response to AVT with cortisol was similar to that following mannitol alone. Normal saline (sham protocol) produced no change in maternal or fetal osmolality. These results indicate that fetal AVT inhibits fetal to maternal water transfer following an osmotic stimulus to the ewe, while cortisol (infused with AVT) tends to counteract the inhibitory effect of AVT on fetal/maternal water transfer.

Catecholamine physiology in the ovine fetus. I. Gestational age variation in basal plasma concentrations.

Fifty-five ewes with chronically catheterized singleton gestations were studied to assess changes in basal concentrations of fetal catecholamines with increasing gestational age. All pregnancies were time dated, and measurements of catecholamines were conducted at least 5 days after placement of fetal catheters when fetal metabolic parameters had normalized. Plasma concentrations of catecholamines were measured by radioenzymatic assay. Additionally, fetal heart rate (FHR) and corrected mean blood pressure were analyzed in 32 of the fetuses for correlation with plasma levels of catecholamines. Multiple regression analysis revealed significant inverse correlations of fetal plasma concentrations of catecholamines with gestational age, as follows: norepinephrine (p less than 0.001), epinephrine (p less than 0.05), and dopamine (p less than 0.01). FHR correlated inversely with gestational age (p less than 0.001) and positively with circulating levels of norepinephrine (p less than 0.001).

Catecholamine physiology in the ovine fetus. III. Maternal and fetal response to acute maternal exercise.

A study was made of the effects of maternal exercise on fetal plasma concentrations of catecholamines in nine ewes with chronically catheterized singleton fetuses at 125 to 137 days' gestation. The ewes were subjected to acute treadmill exercise of 2.5 mph for 45 minutes with continuous recording of maternal and fetal blood pressures. Samples of arterial blood were obtained for measurement of catecholamines, glucose, and blood gases. Changes in blood flow in fetal organs in response to maternal exercise were assessed by injection of radioactive microspheres. The maternal plasma catecholamine responses were related to the severity of the exercise stress as indicated by the index of cardiac effort. The fetal responses did not correlate with maternal cardiac effort. A significant decrease in fetal Po2 with a moderate alkalosis occurred, accompanied by a significant elevation in circulating levels of norepinephrine. At the peak of exercise, there was an increase in fetal renal, adrenal, and placental blood flows, as compared to the control period.

Catecholamine physiology in ovine fetus. II. Metabolic clearance rate of epinephrine.

This study measured the metabolic clearance rate (MCR) of epinephrine (E) in 13 chronically catheterized fetal lambs between 120 and 145 days gestation. The E-MCR was determined by a constant infusion method at an E infusion rate of 0.1 microgram/kg estimated fetal wt. Fetal and maternal arterial blood samples were taken for measurements of catecholamine levels, pH, blood gases, and glucose. There was a significant positive correlation between gestational age and E-MCR (r = 0.87, P less than 0.001). The E production rate in fetuses less than 132 days (n = 6) (1,234 +/- 301 pg/min) was not significantly different from fetuses greater than or equal to 132 days (n = 7) (1,195 +/- 242). Catecholamine infusion resulted in a decrease in pH from a control value of 7.37 +/- 0.01 to 7.31 +/- 0.01 by 15 min of infusion, but there were no significant changes in fetal heart rate or blood pressure. The mean fetal plasma glucose concentration increased 45% above base line at 15 and 20 min and 65% above base line by 30 min of catecholamine infusion. After 60 min of infusion plasma norepinephrine (NE) increased from 380 +/- 60 to 520 +/- 75 pg/ml and plasma dopamine from 100 +/- 20 to 240 +/- 50 pg/ml (both P less than 0.05). These results indicate that E-MCR increases with maturation in the absence of a change in basal E production.

Dietary sodium manipulation and vascular responsiveness during pregnancy in the rabbit.

The interrelationship of sodium intake and blood pressure regulation during pregnancy is not clear. The effects of dietary sodium loading and restriction on plasma levels of catecholamines, mean arterial pressure, and vascular response to two pressor agents, Levophed and angiotensin II, were investigated in 49 chronically prepared primigravid rabbits. Sodium loading increased mean arterial pressure (p less than 0.005), but did not alter the response to either pressor agent. Sodium restriction did not alter mean arterial pressure, but did increase plasma norepinephrine (p less than 0.05) and epinephrine (p less than 0.02). Negative correlations between plasma levels of norepinephrine and vascular response to infusions of both pressor agents were observed during sodium restriction, -0.61 (p less than 0.05) for angiotensin II, and -0.74 (p less than 0.05) for norepinephrine. A similar correlation of -0.81 (p less than 0.05) was observed for angiotensin II in control animals. Norepinephrine appears to play a significant role in blood pressure maintenance and vascular response in pregnancy. This role is enhanced during sodium restriction.

Vasoactive effect of sera from preeclamptic patients.

Investigated was a bioassay method for measurement of vasoactivity in the serum of preeclamptic patients. Intravital microscopy was used to measure the diameter of the principal arteriole and venule in the gastrolienal mesentery of mice before (VD1) and after (VD2) the intravenous injection of sera from preeclamptic primigravid patients and from preeclamptic primigravid patients after treatment with magnesium sulfate (MgSO4). A vasoactive index (VI) was calculated as VD2/VD1. The VIa (vasoactive index for arteriole) of preeclamptic primigravid patients (0.64 +/- 0.39, mean +/- SD) was significantly different (p less than 0.01) from the VIa of normal primigravid patients (0.91 +/- 0.08) and from the VIa of saline controls (0.99 +/- 0.02). Four of the seven preeclamptic primigravid patients had a duration of signs and symptoms dating from the antepartum period (VIa = 0.53 +/-. 0.42), and for three, the diagnosis was made only in the intrapartum period (VIa = 0.77 +/- 0.38). Sera from the MgSO4-treated preeclamptic patients yielded a VIa of 0.91 +/- 0.14, which was not significantly different from that for either the normal primigravid patients or the saline controls. This VIa value was significantly different (p less than 0.01) from the VIa of the untreated preeclamptic patients. These results suggest that here is a vasoactive substance(s) in the sera of preeclamptic patients which may contribute to their arteriolar vasospasm. The magnitude of vasoactivity appears to be related to the duration and severity of preeclampsia but is masked or disappears after treatment of the patient with MgSO4.

The rabbit: a suitable model for investigation of vascular responsiveness during pregnancy.

The decreased vascular response to angiotensin II that characterizes normal pregnancy is lost in pregnancy induced hypertension and associated with an increase in response to norepinephrine. These alterations in vascular responsiveness have not been thoroughly investigated and are poorly understood. Suitable models manifesting physiologic conditions known to exist in human pregnancy have not been satisfactorily demonstrated. We investigated the chronically catheterized and unmedicated rabbit for similarities of four conditions known to occur during human pregnancy. We compared mean arterial pressure and vascular response to angiotensin II and to norepinephrine in 19 non-pregnant and 16 pregnant animals. Plasma levels of angiotensin II, norepinephrine, epinephrine, and dopamine levels were measured and compared. We found striking similarities for conditions investigated in our rabbit model when compared with data reported in the literature for human pregnancy. We conclude the rabbit is a suitable model for investigating alterations of vascular response during pregnancy.

Effect of alpha-adrenergic agonist and antagonist infusion on the umbilical and uterine circulations of pregnant sheep.

The effects of the alpha-adrenergic agonists, norepinephrine and methoxamine, and the alpha-antagonist, phenoxybenzamine, on umbilical and uterine blood flows, fetal and maternal heart rates, arterial and venous pressures were examined in near-term chronic sheep preparations. Norepinephrine injection or methoxamine infusion to either fetus or ewe resulted n a respective unilateral fetal or maternal pressur response associated with bradycardial. Uterine blood flow decreased significantly with alpha-agonist administration to either fetus or ewe. Umbilical blood flow did not change with either, but an increase in calculated umbilicalo vascular resistance did occur after fetal administrations of the alpha-agonist. Thus, both the uterine and umbilical vascular beds are responsive to alpha-agonism, but maternal uteroplacental perfusion appears to be more sensitive. alpha-Blockade in either fetus or mother produced no significant changes in umbilical or uterine blood flows or fetal or maternal perfusion pressure suggesting that basal alpha-adrenergic tone is unnecessary for normal maintenance of either fetal or maternal uteroplacental circulation.

Effects of salbutamol and isoxsuprine on uterine and umbilical blood flow in pregnant sheep.

The effects of salbutamol and isoxsuprine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) were investigated in near-term, nonlaboring chronic sheep preparations. During both intravenous salbutamol and isoxsuprine infusions to the ewe, UtBF and mean maternal arterial pressure decreased significantly. Also, dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate (FHR) during salbutamol infusions, but UmBF and FHR increased during isoxsuprine infusions. During the 120 minute postinfusion recovery period, UtBF rose significantly after the salbutamol infusions but not after the isoxsupine infusions. The effects and structure-activity relationship of these two drugs are comparable to those of ritodrine and fenoterol, two other beta-adrenergic agonists.

Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep.

The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120 minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested as the cause of this UtBF increase.

Fetal pancreatic glucagon responses in glucose-intolerant nonhuman primate pregnancy.

Rhesus monkey pancreatic alpha-cell function in streptozotoc-induced glucose-intolerant pregnancy is similar to that in normal primate pregnancy. Specifically, basal maternal and fetal plasma glucagon levels equate, and the fetal alpha cell does not respond to the glucagonogenic stimulus of either intravenous alanine or insulin-induced hypoglycemia. This contrasts with the accelerated maturation of the fetal beta cell in glucose-intolerant pregnancy, and does not support the concept of functional coupling of the pancreatic islet by a common glucose-based process. Fetal plasma glucagon levels do increase after L-dopa injection to the fetus. These data indicate that alpha cell unresponsiveness is a function of the glucagon-releasing mechanism rather than inadequate hormonal synthesis.

Plasma renin activity in sheep pregnancy after fetal or maternal nephrectomy.

The effect of bilateral fetal or maternal nephrectomy on basal and diuretic-stimulated plasma renin activity (Pra) was examined in 9 chronically catheterized Dorset sheep. After fetal nephrectomy, there was an initial rapid decrease in fetal PRA with t1/2 of 42-84 min, followed by a slower decrement with 1/2 350-720 min. There was no change in maternal PRA during this period. Similarly, after maternal nephrectomy, the decrease in maternal PRA had two exponential components and there was no associated change in fetal PRA. These data, and the maternal and fetal PRA responses to intravenous furosemide, have demonstrated that renin does not cross the sheep placenta and that fetal PRA is independent of the maternal PRA level.