Valerie M. Parisi

Routine umbilical cord blood gas determinations

Between 1986 and 1988, 1924 term nulliparous patients with spontaneous onset of labor were studied to assess the importance of obtaining umbilical cord blood gas levels on all deliveries. The umbilical cord arterial and venous pH values (expressed as mean +/- 2 SD) were 7.24 +/- 0.14 (n = 1694) and 7.32 +/- 0.12 (n = 1820), respectively. The incidence of newborn depression (1- or 5-minute Apgar score less than 7) was 14.1%; of these depressed newborns, the incidence of normal umbilical cord arterial pH values (greater than or equal to -2 SD) was 77.8%. Of the vigorous newborns, there was a 2.1% incidence of umbilical cord arterial blood acidemia. Umbilical cord arterial blood acidemia in vigorous newborns was not highly predictive of specific morbidity in the immediate newborn period. Regression analysis demonstrated the umbilical cord arterial pH to correlate best with the Apgar scores when compared with all other arterial or venous blood gas measurements. We reached the following conclusions: (1) that obtaining cord arterial pH values in vigorous newborns should be considered since the values will provide objective documentation or normal fetal acid base balance in 98% of infants. (2) Only a cord arterial pH determination is recommended since it reflects fetal or newborn status more accurately than all other measurements. Additional measurements increase the likelihood of abnormal results and do not contribute to neonatal management. (3) An umbilical cord blood pH value is extremely useful in ruling out the diagnosis of birth asphyxia in the depressed newborn.

The effect of magnesium sulfate tocolysis on the fetal biophysical profile

The biophysical profile has proved to be a valuable tool for the assessment of fetal well-being, independent of gestational age. Magnesium sulfate is commonly used as a tocolytic agent, yet relatively little is known about its effects on the biophysical activities of the fetus. To investigate the effects of magnesium sulfate on the biophysical profile, we performed serial studies on patients who received tocolytic therapy with this agent because of preterm labor. A total of 16 women with 22 fetuses at 26 to 34 weeks gestation in spontaneous preterm labor were studied. An initial biophysical profile was performed at the time of admission, and a second examination was performed when maternal serum magnesium levels reached 6 to 8 mg/dl. On admission all fetuses had reactive nonstress test results and 21 of 22 (95%) demonstrated sustained fetal breathing movements. With magnesium sulfate tocolysis, 50% of fetuses had nonreactive nonstress test results, and only 4 of 22 (18%) demonstrated sustained fetal breathing movements. Fetal tone, gross body movements, and amniotic fluid volume were found to be unaffected by magnesium sulfate tocolysis.

Fetoplacental vascular responses to prostacyclin after thromboxane-induced vasoconstriction

The vasodilator prostacyclin is produced by fetal tissues and may serve to protect umbilical blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by a thromboxane mimic (U-46619). Fetal regional blood flow was measured by the radioactive microsphere technique in six unanesthetized, near-term ovine fetuses. Measurements were made in the control period, again 20 minutes after a fetal infusion of U-46619 was begun, and finally 20 minutes after prostacyclin was added to the U-46619 infusion. Mean arterial pressure rose significantly in response to U-46619 (38 +/- 1 to 51 +/- 2 mm Hg, p less than 0.01) and returned to baseline after prostacyclin (42 +/- 2 mm Hg). Renal resistance was increased from 0.16 +/- 0.01 to 0.22 +/- 0.01 mm Hg.ml-1.min.100 gm-1 (p less than 0.05) by U-46619 and decreased significantly (p less than 0.05) below baseline by addition of prostacyclin (0.10 +/- 0.02 mm Hg.ml-1.min.100 gm-1). Placental resistance also increased significantly (p less than 0.03) in response to U-46619 (from 0.15 +/- 0.01 to 0.21 +/- 0.01 mm Hg.ml-1.min.kg-1 fetal weight) but was further increased to 0.29 +/- 0.03 mm Hg.ml-1.min.kg-1 fetal weight by the addition of prostacyclin. Umbilical placental blood flow decreased significantly (p less than 0.03) when prostacyclin was added to U-46619 (315 +/- 40 to 195 +/- 30 ml.min-1.kg-1 fetal weight). Whereas U-46619 had no effect on fetal arterial blood gases, the addition of prostacyclin resulted in significant fetal acidosis (p less than 0.03). We conclude that thromboxane mimic causes fetal hypertension and renal and placental vasoconstriction. Prostacyclin reverses hypertension and renal vasoconstriction but, unexpectedly, worsens fetal placental vasoconstriction produced by thromboxane. It is likely that the observed fetal acidosis is a result of compromised placental function.

Placental vascular responses to nicardipine in the hypertensive ewe

Calcium channel blockers are arterial vasodilators effective in the treatment of hypertension. Therefore nicardipine, a dihydropyridine calcium channel blocker, should modulate angiotensin II-induced vasoconstriction. Regional blood flows were measured with radioactive microspheres in five chronically catheterized near-term ewes both before and 15 minutes after maternal infusion of angiotensin II at 5 micrograms/min. Nicardipine was then administered intravenously at 20 micrograms/kg/min over 2 minutes while the angiotensin II infusion was maintained. Blood flows were measured after 5 minutes. Maternal blood pressure levels were increased by angiotensin II from 83 +/- 4 mm Hg to 114 +/- 5 mm Hg, and were decreased to 70 +/- 4 mm Hg by nicardipine (p less than 0.05). Nicardipine also reversed angiotensin II-induced vasoconstriction in the renal and endomyometrial vascular beds (p less than 0.05). Unexpectedly, however, nicardipine worsened placental vasoconstriction caused by angiotensin II, as placental blood flow fell from 242 +/- 32 ml.min-1.kg-1 fetal weight to 128 +/- 7 ml.min-1.kg-1 fetal weight (p less than 0.05), and placental resistance increased from 0.48 +/- 0.04 mm Hg.ml-1.min.kg-1 fetal weight to 0.55 +/- 0.05 mm Hg.ml-1.min.kg-1 fetal weight (p less than 0.05). Nicardipine reverses angiotensin II-induced vasoconstriction systemically and in the kidney and uterus of the pregnant ewe, but does not reverse placental vasoconstriction and may significantly alter fetal cardiorespiratory status.

Fetal vascular responses to prostacyclin

Prostacyclin is a potent vasodilator produced by both maternal and fetal tissues that dilates the umbilical placental vasculature in vitro. To test the hypothesis that prostacyclin dilates the fetal placental circulation in vivo, we measured blood flow by the radioactive microsphere technique in six unanesthetized near-term ovine fetuses before and during prostacyclin infusion. Fetal mean arterial pressure fell 15% from 35 +/- 3 to 31 +/- 3 mm Hg (p less than 0.05) during prostacyclin infusion, and heart rate increased from 182 +/- 6 to 208 +/- 19 beats/min (p less than 0.05). Placental blood flow changed from 240 +/- 58 to 191 +/- 46 ml.min-1.kg-1 fetal weight (p = 0.07), whereas vascular resistance was unchanged (0.16 +/- 0.04 to 0.18 +/- 0.06 mm Hg.ml-1.min.kg fetal weight). Fetal arterial pH decreased from 7.33 +/- 0.03 to 7.28 +/- 0.02 (p less than 0.05) during prostacyclin infusion, with a significant decrease in base excess from -1.2 +/- 1.4 to -3.1 +/- 1.6 (p less than 0.05) and a trend toward hypercarbia (p = 0.07). We conclude that in vivo administration of prostacyclin to the ovine fetus does not cause fetal placental vasodilation and does cause a significant fetal acidemia. The mechanism for these unexpected observations is likely shunting of blood away from the placenta to other organs in the face of systemic vasodilation.

Effect of rapid intravenous crystalloid infusion on uteroplacental blood flow and placental implantation-site oxygen delivery in the pregnant ewe

OBJECTIVEnOur purpose in this study was to investigate the effects of rapid intravenous crystalloid infusion on placental implantation-site blood flow and oxygen delivery in the near-term pregnant ewe.nnnSTUDY DESIGNnMaternal left ventricular, femoral arterial and venous, and bilateral fetal hind limb arterial catheters were placed in nine near-term ewes 5 days before the start of the study. Maternal and fetal arterial blood gas values, maternal hemodynamic measurements, and maternal organ blood flows (microsphere technique) were obtained before and after the intravenous infusion of 2.0 to 2.5 L of normal saline solution. Myometrial and placental implantation-site vascular resistances and oxygen delivery were calculated. The t test for paired comparisons was used for statistical analysis, with p < or = 0.05 considered significant.nnnRESULTSnSignificant postinfusion increases in maternal mean arterial pressure, placental implantation-site blood flow, and skin, skeletal muscle, and renal blood flows were recorded. In the six animals that demonstrated a fall in hemoglobin concentration, a significant increase in placental implantation-site oxygen delivery and a significant decrease in placental implantation-site vascular resistance were also seen. No significant changes were seen in myometrial blood flow or myometrial vascular resistance.nnnCONCLUSIONnRapid intravenous crystalloid infusion selectively increases placental implantation-site blood flow in the near-term pregnant ewe and may improve oxygen delivery to the fetus, especially if hemodilution occurs.

The effect of fetal sepsis on umbilical cord blood gases

The relationship between fetal sepsis and acid-base status is unknown. We hypothesized that in utero sepsis would result in fetal metabolic acidemia. In a retrospective study during a 38-month period, the acid-base status at birth of neonates with in utero sepsis, documented by positive blood cultures, was reviewed. Compared with term neonates, preterm neonates had a 22-fold increase in the risk of bacteremia at birth. In spite of this increased risk of sepsis, there was no significant alteration in arterial pH in preterm septic neonates when compared with preterm controls. Fetal sepsis at term was accompanied by a statistically significant reduction in arterial pH (7.21 +/- 0.07) compared with controls (7.26 +/- 0.06, p less than 0.05). When controlled for other variables, the decrease in arterial pH at term was correlated with an increased duration of labor (7.3 +/- 0.7 in controls vs 10.8 +/- 0.9 hours in neonates with sepsis, p less than 0.05). The classic predictors of chorioamnionitis were found to be poor prognostic indicators of fetal bacteremia. Fetal sepsis at term is associated with a deterioration in the fetal acid-base status and a prolongation of labor.

The ovine fetal sympathoadrenal response to the maternal administration of methamphetamine

OBJECTIVEnWe hypothesized that maternally administered methamphetamine would alter fetal sympathoadrenal activity.nnnSTUDY DESIGNnSix chronically catheterized near-term pregnant ewes received an intravenous bolus injection of methamphetamine (1.25 mg/kg). Maternal and fetal arterial blood gas values, glucose, insulin, lactate, and catecholamines were measured in the control period and at 15, 30, 60, 90, 120, and 180 minutes after methamphetamine.nnnRESULTSnFetal PO2 decreased from 21.4 +/- 1.9 mm Hg at control measurement to 15.3 +/- 3.3 mm Hg after 60 minutes (p < 0.05). Fetal pH declined from 7.35 +/- 0.014 at control to 7.29 +/- 0.024 after 180 minutes. Fetal plasma glucose rose from 15.3 +/- 2.4 mg/dl at control to peak at 51.2 +/- 6.8 mg/dl at 120 minutes. Insulin levels increased from a control of 40.5 +/- 8.06 to a peak of 128 +/- 46 microIU/ml at 180 minutes (p < 0.05). Lactate levels increased from a baseline of 33.5 +/- 2.0 mg/dl to 92.3 +/- 22.8 mg/dl at 180 minutes. Fetal catecholamines rose from a baseline of 153 +/- 20.2 pg/ml for epinephrine and 226 +/- 18.5 pg/ml for norepinephrine to maximum values of 518 +/- 87.3 and 661 +/- 59.3 pg/ml at 15 minutes (p < 0.05), declining thereafter.nnnCONCLUSIONSnMaternal administration of methamphetamine is associated with a short-term increase in circulating fetal catecholamines followed by hyperglycemia, lactacidemia, and hyperinsulinemia. These findings suggest that the alteration of fetal sympathoadrenal activity may contribute to the various perinatal complications associated with methamphetamine use.

Placental thromboxane and prostacyclin production in an ovine diabetic model

We hypothesized that streptozocin-induced ovine diabetes would cause alterations in the placental production of thromboxane and prostacyclin. With a tissue incubation technique, we examined the placental production of thromboxane and prostacyclin in cotyledons from seven normal near-term ewes (127 +/- 3 days gestation) and six streptozocin-induced diabetic ewes (125 +/- 3 days gestation). Diabetic status was verified with serial fasting blood glucose assessments. Placental tissue was incubated in Dulbeccos modified Eagles medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide. Samples were collected at 0, 1, 2, 4, 8, 20, 32, and 48 hours. Radioimmunoassay of the stable metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were used to determine thromboxane and prostacyclin production, respectively. Placental thromboxane production was reduced in diabetic animals when compared with control animals (5.63 +/- 2.81 vs 7.32 +/- 1.37 pg/mg per hour, respectively; p less than 0.05). Prostacyclin production was also significantly reduced in the diabetic placentas compared with control placentas (11.44 +/- 4.06 vs 16.29 +/- 4.59 pg/mg per hour, respectively; p less than 0.05). We conclude that the ovine placenta produces thromboxane and prostacyclin. The ovine thromboxane production rate is comparable to that of the human placenta but the prostacyclin production rate is approximately two to three times higher. The observed decrease in the placental production of thromboxane and prostacyclin may reflect an adverse effect of hyperglycemia directly on eicosanoid production or indirectly through decreased placental cellular proliferation.

Leukotrienes, But Not Hydroxyeicosatetraenoic Acids, Lower Blood Pressure in Pregnant and Postpartum Rhesus Monkeys

Leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) exert vasoactive effects in vitro and in nonpregnant individuals. They are produced by the human placenta, and may therefore, affect maternal blood pressure during pregnancy. To evaluate this, LTs and HETEs were injected into the lower vena cava to mimic the systemic route of placentally produced hormones. Tethered, chronically catheterized pregnant and postpartum rhesus monkeys (6-9 Kg) were used (n = 6). HETEs had no effect. LTB4, LTC4 or LTD4 (5-20 μg, i.v., bolus) decreased maternal systemic arterial blood pressure (systolic by 9 mmHg, diastolic by 7 mmHg) from 15 to 90 sec. after administration. A combination of LTB4, LTC4, LTD4 (2 μg each, i.v.) also lowered blood pressure suggesting their effects might be additive. FPL 55,712 (a cysteine LT receptor blocker, 10 mg, i.v., bolus) increased blood pressure (systolic by 15 mmHg, diastolic by 10 mmHg) demonstrating a role for endogenous LTs to lower blood pressure. Higher, doses of the LTs, (10...