Christos G. Hatjis

Systemic tocolysis for premature labor is associated with an increased incidence of pulmonary edema in the presence of maternal infection

Our hypothesis is that systemic tocolysis of patients in premature labor is associated with a higher incidence of pulmonary edema in the presence of maternal infection. Over a 64-month period, medical records of all patients with a diagnosis at discharge of pulmonary edema or congestive heart failure were reviewed. There were 27 cases of pulmonary edema, 16 of which (59.3%) were associated with treatment of preterm labor. The incidence of pulmonary edema in patients receiving systemic tocolysis for treatment of preterm labor was significantly higher than that in our general obstetric population (3.04% versus 0.05%). Of the 527 patients receiving tocolysis, there was evidence of maternal infection in 52. The incidence of pulmonary edema was higher in the presence of maternal infection than in its absence (11/52 or 21% versus 5/475 or 1%, p = 0.0000). We conclude that there is a very strong association between the development of pulmonary edema and the presence of maternal infection in patients being treated for premature labor with systemic tocolysis.

Effect of placental laterality on uterine artery resistance and development of preeclampsia and intrauterine growth retardation

We studied 153 pregnant women with normal pregnancies and 147 women with complicated pregnancies (diabetes, hypertensive disorders, and intrauterine growth retardation) to evaluate the association of placental location and the development of preeclampsia, intrauterine growth retardation, and uterine artery resistance. The placental location was determined by real-time ultrasonography, and the uterine artery resistance was determined by continuous-wave Doppler flow velocity waveform analysis. In the presence of preeclampsia or intrauterine growth retardation, up to 75% of the patients had unilaterally located placentas and 25% central placentas, whereas in the absence of these two conditions only 51% of the patients had unilateral and 49% central placentas ( p p p p

Atrial natriuretic peptide receptors in normal human placentas

We studied whether plasma membranes from normal human placentas contain receptors for atrial natriuretic peptide. We identified specific, high-affinity, low-capacity atrial natriuretic peptide binding sites in the nonbrush border, microsomal fraction presumed to originate from cellular membranes near the fetal circulation. In contrast, no atrial natriuretic peptide binding sites could be identified in the brush border; the latter is exposed to maternal blood in the intervillous space. The presence of atrial natriuretic peptide binding sites in human placentas suggests that atrial natriuretic peptide may be involved in fluid and electrolyte homeostasis in human gestation.

Atrial natriuretic factor maternal and fetal concentrations in severe preeclampsia.

There is a reduction in intravascular volume in patients with preeclampsia. Since the secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention, we sought to determine whether circulating maternal plasma atrial natriuretic factor concentrations were lower in patients with preeclampsia compared to normal pregnant women. The level of alpha-human atrial natriuretic factor was measured by a specific radioimmunoassay. Maternal venous concentrations of a alpha-human atrial natriuretic factor were higher in patients with severe preeclampsia (116.12 +/- 13.37 pg/ml) than in normal pregnant women (80.30 +/- 4.02 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher in fetuses born to patients with severe preeclampsia (197.68 +/- 29.10 pg/ml) than normal control subjects (118.00 +/- 12.52 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher than umbilical or maternal venous concentrations. In cases of severe preeclampsia, despite the presumed volume changes, maternal atrial natriuretic factor concentrations are higher than in normal pregnant women. The fetus appears to produce its own atrial natriuretic factor. Umbilical artery atrial natriuretic factor concentrations in fetuses born to preeclamptic mothers are higher than those seen in normal control subjects.

β-Adrenergic-receptor and adenylate cyclase properties in pregnant and nonpregnant guinea pig myometrium

Stimulation of myometrial beta-adrenergic receptors by agonists results in myometrial relaxation through adenylate cyclase-dependent mechanisms. Their activity is modulated by local or systemic estrogen-progesterone milieu. During pregnancy, guinea pigs demonstrate an ovarioplacental shift for progesterone production at less than or equal to 0.35 gestation and a gradual increase in estrogen levels. To investigate whether these changes affect myometrial beta-adrenergic-receptor and adenylate cyclase properties, we directly characterized beta-adrenergic receptors and adenylate cyclase in myometrial plasma membranes from time-dated pregnant (term 65 days), postpartum, and nonpregnant virgin guinea pigs by well-established in vitro methods. In all animals, there appeared to be a high-affinity, low-capacity, single class of binding sites with pharmacologic specificities consistent with the beta 2-adrenergic-receptor subtype. The dissociation constants of these beta-adrenergic receptors were significantly decreased in pregnant animals at approximately greater than or equal to 0.80 gestation when compared to pregnant animals at 0.35 to 0.40 gestation, nonpregnant animals, and postpartum animals. Moreover, the total number of beta-adrenergic receptors was significantly higher at greater than or equal to 0.80 gestation than in the other groups. Basal adenylate cyclase activity increased in animals from 0.35 to greater than or equal to 0.8 gestation and was higher than that of postpartum animals and nonpregnant animals. The degree of adenylate cyclase stimulation by (-)isoproterenol was higher at term than at an earlier point in gestation or in nonpregnant and postpartum animals. These results indicate that, with advancing gestation in pregnant animals, there is an up-regulation of beta-adrenergic-receptor and adenylate cyclase function.

Addition of magnesium sulfate improves effectiveness of ritodrine in preventing premature delivery

From October, 1981, to July, 1983, 225 patients were evaluated for premature labor at Forsyth Memorial Hospital. Sixty-five of these patients were considered to be candidates for intravenous ritodrine treatment. Of this group, 24 patients were successfully treated and had pregnancy prolongation ranging from 1 to 17 weeks. Forty-one patients did not respond to maximal intravenous ritodrine therapy (300 to 350 micrograms/min). Eleven patients subsequently delivered within 24 to 48 hours of treatment initiation. The remaining 30 patients received intravenous magnesium sulfate (1 to 3 gm/hr) in addition to intravenous ritodrine. Eighteen patients responded favorably to this combination treatment and had pregnancy prolongation ranging from 1 to 11 weeks. Twelve patients delivered within 1 week from treatment initiation. In all cases where pregnancy prolongation was achieved, birth weight and neonatal outcome were significantly improved compared to patients who did not respond to either intravenous ritodrine alone or intravenous ritodrine and magnesium sulfate combination. Treatment related maternal/fetal complications were not significantly different in the various groups examined. From the foregoing we conclude that, in a select group of patients in premature labor not responding to conventional ritodrine therapy, magnesium supplementation in pharmacologic doses could have a beneficial effect with respect to pregnancy outcome.

C-reactive protein: a limited test for managing patients with preterm labor or preterm rupture of membranes?

C-reactive protein has been used to identify patients at high risk for infectious morbidity with preterm labor or preterm rupture of membranes. In this article we report on 104 patients with preterm labor symptoms (n = 45) or preterm rupture of the membranes (n = 59) and serial evaluations of C-reactive protein measured by latex agglutination and laser nephelometry. The simple, inexpensive latex method appears comparable to the laser method in predicting infectious morbidity and can be used clinically. Elevated C-reactive protein values before delivery predict infectious morbidity in only 8% to 29% of patients, and up to 18% of patients with serious infections may be misdiagnosed as having normal C-reactive protein values before delivery.

Changes in placental atrial natriuretic peptide receptors associated with severe toxemia of pregnancy

We have previously demonstrated the presence of atrial natriuretic peptide (ANP) specific receptors in normal human placentas. Since toxemia of pregnancy may affect important metabolic, transport and hemodynamic functions of placentas, we have asked the question whether binding properties of human placental ANP receptors are changed in patients with severe toxemia of pregnancy when compared to normal patients. ANP receptors in plasma membranes from normal and severely toxemic patients were characterized by in vitro radioligand assays utilizing [125I]-alpha-hANP. In all cases, we identified specific, high affinity, low capacity ANP binding sites in a microsomal fraction of human placentas. Although the total concentration of receptors did not differ between the two groups, the dissociation constant, KD, was significantly higher in placentas from severely toxemic patients than from normal controls. From the above we conclude that placental ANP receptors are dynamically modulated and their characteristics may be altered in severe toxemia of pregnancy.

Up-regulation of guinea pig myometrial β-adrenergic receptors by intrauterine estradiol and progesterone pellets

The effect of intrauterine implantation of 17 beta-estradiol and progesterone on the concentration and affinity of myometrial beta-adrenergic receptor were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either 17 beta-estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenergic receptors were characterized by use of (-)-iodine 125-cyanopindolol as the specific beta-adrenergic receptor ligand. On comparison with the control group, administration of 17 beta-estradiol or progesterone resulted in a severalfold increase in the concentration (Bmax) of myometrial beta-adrenergic receptor and a lesser but significant increase in the dissociation constant, KD. Although a combination of 17 beta-estradiol and progesterone treatment increased the concentration and the dissociation constant of beta-adrenergic receptors, it did not result in any synergistic or additive effect. We conclude that intrauterine administration of these sex steroid hormones, directly or indirectly, modulates myometrial beta-adrenergic receptor concentrations and affinity.

Up-regulation of guinea pig myometrial adenylate cyclase activity by intrauterine estradiol and progesterone pellets

The effects of intrauterine implantation of 17 beta-estradiol and progesterone on basal and stimulated adenylate cyclase activity in guinea pig myometria were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Guanine nucleotides resulted in a significant increase in basal enzymatic activity. The extent of enzymatic stimulation in estradiol-treated animals was significantly higher than that observed in either controls, animals receiving progesterone, or a combination of estradiol and progesterone. Sodium fluoride stimulation occurred in all treatment groups to a similar degree. However, guanine nucleotides resulted in a significant decrease in percent stimulation of maximal sodium fluoride-stimulated enzymatic activity. Finally, beta-adrenergic receptor-mediated enzymatic activity, as assayed by isoproterenol stimulation, was higher in those animals that received estradiol implants than in controls or the other two hormonally treated groups. Intrauterine administration of these sex steroid hormones, directly or indirectly, modulates myometrial adenylate cyclase activity.