Carl P. Weiner

Direct treatment of fetal supraventricular tachycardia after failed transplacental therapy

Digitalization by direct intramuscular injection of the fetus successfully controlled supraventricular tachycardia at 24 weeks gestation after more traditional intensive trials of transplacental therapy with digoxin, verapamil, and procainamide, either separately or in combination, had failed. The fetal pharmacokinetics were calculated from fetal blood samples obtained by cordocentesis. No clear evidence of placental transfer of digoxin administered to the mother could be found despite a digoxin concentration in the mother that ranged from 1.8 to 2.6 ng/ml for 4 days. After direct fetal digitalization we calculated that the coefficient of elimination for digoxin from the fetus was 0.0463 h-1, and digoxin elimination half-life was 15.9 hours. The latter time span is substantially less than the 50-hour half-life previously reported in newborn infants with low birth weight. The fetal/maternal concentration ratio of procainamide was 0.914. However, maternal clearance of procainamide (9.7 ml/kg-1/min-1) was twice as long as the clearance reported for nonpregnant patients undergoing fast acetylation. We conclude first, that at least in the dose of this ill fetus, little digoxin administered to the mother crossed the placentae; and second, that while direct fetal therapy with digoxin is effective, the necessary frequent number of injections render this therapy impractical. Direct fetal digitalization should probably be reserved for the preterm fetus who has evidence of heart failure and has not responded to maternally administered therapy other than digoxin.

The role of serotonin in the genesis of hypertension in preeclampsia

While it is generally accepted that preeclampsia is a disease of the microvasculature characterized by an imbalance between prostacyclin and thromboxane and that the evidence for enhanced responsiveness to some vasopressors is present weeks before clinical disease, the specific cause of the hypertension characterizing the syndrome is unknown. A number of endogenous vasopressor substances have been examined without conclusive findings. Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of preeclamptic hypertension. This information is summarized and a possible mechanism of delivery and action is suggested.

Effects of Magnesium Sulfate Infusion Upon Plasma Prostaglandins in Preeclampsia and Preterm Labor

Objective: Recent investigation has shown that magnesium stimulates the release of prostacyclin from confluent endothelial cell cultures. The goal of this study was to determine the effect of magnesium sulfate infusion on the peripheral concentrations of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) and 6-keto-prostaglandin F1α (6-keto-PGF1α the stable metabolite of prostacyclin) in women with either preeclampsia or preterm labor. We hypothesized that plasma prostacyclin concentrations would increase during magnesium sulfate infusion in women with preeclampsia to a greater extent than in women with preterm labor.Methods: Twenty-one women with preeclampsia and 14 women in preterm labor were enrolled in a prospective study following transfer to a tertiary center. Blood samples were obtained prior to initiating the magnesium sulfate infusion, immediately after a 4-g load and 2 h later during a maintenance infusion of 2 g/h.Main Outcome Measures: 6-keto-PGF1α PGE2 and PGF2α concentrations were measured a...

The interaction between serotonin and angiotensin II in the chronically instrumented guinea pig and its alteration by indomethacin

We examined the effect of a subthreshold infusion of serotonin on the angiotensin II pressor response in the chronically instrumented pregnant and nonpregnant guinea pig before and after administration of a prostaglandin synthesis inhibitor. Arterial blood pressure was significantly lower in the pregnant animal (p = 0.0135). An infusion of serotonin, which failed to alter the blood pressure, pulse, or uterine artery flow velocity, significantly increased the pressor response to angiotensin II infused at 3.5, 7.5, 14.5, and 29 ng/kg/min in both the pregnant (p = 0.0001) and, to a lesser degree, the nonpregnant animal (p = 0.004). Pretreatment with indomethacin heightened the angiotensin pressor effect significantly in the pregnant group (p = 0.0001) and to a near-significant degree in the nonpregnant group (p = 0.074). However, indomethacin enhanced the angiotensin II-serotonin synergism only in the pregnant animal (p = 0.0008). The angiotensin II-serotonin synergism persisted after pretreatment with the sympathetic blocking agent bretylium tosylate. We concluded that serotonin augments the pressor effect of angiotensin II in the pregnant and nonpregnant guinea pig; however, this synergism is potentiated by the inhibition of prostaglandin synthesis only in the pregnant animal.

BLOOD TRANSFUSION FOR HAEMOLYTIC DISEASE AS A CAUSE OF LEUKOCYTOSIS IN THE FETUS

We evaluated the effect of fetal intravascular transfusion (IVT) of leukocyte‐poor red blood cells to correct fetal anaemia due to haemolytic disease on the fetal leukocyte count in 153 patients. Initial, mid‐transfusion, and closing haematological studies were obtained when possible. The effect on leukocyte subsets was evaluated by the manual differential count. Fetal leukocyte count increased an average of 18·0 per cent during all IVTs (P<0·01), despite the dilutional effect of the transfusion. The degree of leukocytosis increased with subsequent transfusions. The smallest (10·1 per cent) change occurred during the initial transfusion. A 41·8 per cent increase was noted during the sixth procedure. There was no relation between leukocytosis and gestational age, volume of transfusion, changes in umbilical vein pressure, or hydrops. Forty‐two per cent of the increase was due to expansion of the neutrophil pool and 22 per cent was due to expansion of the monocyte pool. The neutrophil count increased 29 per cent (P<0·01) and monocytes increased 64·7 per cent (P<0·001). There was no change in eosinophil and lymphocyte counts. Both an immune aetiology and an effect of inflammatory agents may contribute to this leukocytosis.

Effect of intravenous β-sympathomimetic tocolysis on human fetal serum erythropoietin levels

OBJECTIVEnThe major stimulus for erythropoietin production is tissue hypoxia. We sought to investigate the relationship of beta-sympathomimetic administration for tocolysis and fetal serum erythropoietin.nnnSTUDY DESIGNnUmbilical cord blood was obtained from infants whose mothers received intravenous beta-sympathomimetic tocolysis and who were delivered at < or = 34 weeks gestation. Serum erythropoietin was measured by radioimmunoassay. On the basis of the presumed 2- to 4-hour half-life of fetal erythropoietin, the infants were divided into two groups. In group 1 (n = 16) beta-sympathomimetic therapy was discontinued < 24 hours before delivery; in group 2 (n = 11) it was discontinued > or = 24 hours before delivery.nnnRESULTSnGroup 1 fetuses had significantly higher erythropoietin levels than did group 2 fetuses (37.3 vs 13.9 mU/ml, p = 0.02). The duration of beta-sympathomimetic tocolysis and the maximum infusion rate were not different. The two groups did not differ in gestational age, birth weight, route of delivery, presence of labor, or duration of first or second stage of labor.nnnCONCLUSIONSnWe speculate that intravenous beta-sympathomimetic tocolytic therapy stimulates fetal erythropoietin production by decreasing fetal oxygenation as a result of the reversible fetal metabolic effects of the tocolysis. These data suggest that beta-sympathomimetic tocolysis should be undertaken cautiously if fetal compromise is suspected, fetal well-being should be assessed carefully if tocolysis is undertaken, and treatment should be discontinued promptly if a clear benefit is not realized.

The plasma renin-angiotensin system in preeclampsia: Effects of magnesium sulfate

&NA; Two groups of women were studied in a prospective longitudinal fashion to determine the effects of a 2.5‐hour infusion of magnesium sulfate upon the renin‐angiotensin system. Serum magnesium concentration, angiotensin‐converting enzyme concentration, and plasma renin activity were measured at uniform intervals in women with either preeclampsia or preterm labor. Plasma renin activity was significantly lower (3.9 ± 2.2 versus 6.1 ± 1.8 ng/mL/minute; P = .004) and angiotensin‐converting enzyme significantly higher (47.1 ± 14 versus 34.0 ± 10 U/mL; P = .008) in women with preeclampsia than in those with preterm labor. Magnesium infusion was associated with a sustained decline in plasma renin activity in preeclamptic women (P = .003). A transient decline in angiotensin‐converting enzyme (P = .009) was observed in women with preeclampsia, but not with preterm labor. In contrast to the sustained change in plasma renin activity, angiotensin‐converting enzyme concentration returned to baseline activity levels by 2.5 hours. A nonsignificant negative relationship (P = .06) was noted between angiotensin‐converting enzyme and gestational age in subjects with preeclampsia. We conclude that a short‐term infusion of magnesium sulfate leads to a sustained decline in plasma renin activity in preeclamptic women, but exerts no sustained effect on angiotensin‐converting enzyme in women with either preeclampsia or preterm labor. (Obstet Gynecol 73:934, 1989)

The Effect of Intravenously Administered 2-Chloroprocaine Upon Uterine Artery Blood Flow Velocity in Gravid Guinea Pigs

The purpose of the present study was to assess the effect of intravenously administered 2-chloroprocaine upon uterine artery blood flow velocity (UBFV) in gravid guinea pigs. Ten experiments were performed in ten chronically instrumented animals between 0.7 and 0.9 of timed gestation. Each animal received four solutions of 2-chloroprocaine in random order: 1) 0.67 mg/kg; 2) 1.34 mg/kg; 3) 2.0 mg/kg; and 4) 1.34 mg/kg, with epinephrine 0.2 microgram/kg. Six animals received a fifth solution, 0.2 ml of saline control. 2-Chloroprocaine 1.34 mg/kg significantly increased maternal mean arterial pressure (MMAP) at 30 s after injection, and 2-chloroprocaine 2.0 mg/kg significantly increased MMAP through 2 min. 2-Chloroprocaine 1.34 mg/kg, with epinephrine 0.2 microgram/kg, also significantly increased MMAP through 2 min. No other solution significantly altered MMAP. 2-Chloroprocaine 2.0 mg/kg significantly decreased UBFV at 30 s after injection. 2-Chloroprocaine 1.34 mg/kg, with epinephrine 0.2 microgram/kg, significantly decreased UBFV through 2 min. No other solution significantly altered UBFV. The authors conclude that iv administration of 2-chloroprocaine with epinephrine significantly decreased UBFV in pregnant guinea pigs. In contrast, only the largest dose (i.e., 2.0 mg/kg) of 2-chloroprocaine alone transiently decreased UBFV. These data suggest that, in doses up to 1.34 mg/kg, 2-chloroprocaine alone may not decrease uterine blood flow when used as a marker for intravenous injection in obstetric patients.

Effect of Intravenous Epinephrine on Uterine Artery Blood Flow Velocity in the Pregnant Guinea Pig

The purpose of the present study was to determine the effect of intravenously administered epinephrine on the maternal cardiovascular response and uterine artery blood flow velocity (UBFV) in the pregnant guinea pig. Epinephrine (0.2, 0.5, and 1.0 µg/kg) and lidocaine (0.4 mg/kg, with and without 0.2 µg/kg of epinephrine) were administered intravenously to seven chronically instrumented pregnant guinea pigs near term. Lidocaine without epinephrine did not significantly alter maternal heart rate (MHR), maternal mean arterial pressure (MMAP), or UBFV. Epinephrine, with and without lidocaine, resulted in a transient decrease in MHR. Further, epinephrine, with and without lidocaine, resulted in significant elevations in MMAP and significant, dose-related reductions in UBFV. Mean (±SEM) UBFV was 72 ± 4%, 56 ± 4%, and 40 ± 5% of baseline at 30 s after administration of epinephrine, 0.2, 0.5, and 1.0 µg/kg, respectively. It is concluded that these small intravenous boluses of epinephrine result in significant, although transient, reductions in UBFV in the pregnant guinea pig.

The Effect of Ephedrine Upon Uterine Artery Blood Flow Velocity in the Pregnant Guinea Pig Subjected to Terbutaline Infusion and Acute Hemorrhage

The purpose of the present study was to determine the effect of intravenously administered ephedrine upon uterine artery blood flow velocity (UBFV) in the gravid guinea pig subjected to terbutaline infusion and acute hemorrhage. Ephedrine, 1.0 mg/kg, was administered intravenously to ten chronically instrumented pregnant guinea pigs near term, before and after intravenous infusion of terbutaline and acute hemorrhage. Before terbutaline and hemorrhage, ephedrine increased maternal mean arterial pressure (MMAP) by 30 ± 1% (P = .0001) and 17 ± 1% (P = .0001) at 30 s and at 1 min after injection, respectively; UBFV was decreased by 10 ± 4% (P < .01) and 14 ± 4% (P < .01) at 1 min and at 90 s after injection, respectively. Infusion of terbutaline (1.5–6.0 ug · kg−1 · min−1) increased maternal heart rate (MHR) by 22 ± 1% (P = .0001), decreased MMAP by 13 ± 2% (P = .0001), and decreased UBFV by 24 ± 3% (P = .0001). During hypotension resulting from acute hemorrhage, ephedrine, 1.0 mg/kg, was superior to placebo in restoring MMAP and UBFV toward the prebleed values. The authors concluded that ephedrine, 1.0 mg/kg, results in a small, transient decrease in UBFV in the normotensive gravid guinea pig. However, ephedrine aids restoration of UBFV in the gravid guinea pig rendered hypotensive by acute hemorrhage during terbutaline infusion.