Guillermo J. Valenzuela

Placental passage of the oxytocin antagonist atosiban

OBJECTIVEnWe wanted to determine the degree of placental transfer of atosiban (Antocin), an oxytocin antagonist, in pregnant women at term. We also assessed the effects of the infusion on umbilical cord blood gases at birth and the maternal hematocrit drop after cesarean section.nnnSTUDY DESIGNnEight women undergoing elective cesarean section at term were studied. Each received an infusion of 300 micrograms/min of atosiban over 208 to 443 minutes; the infusion was continued up to the time of cord clamping. Uterine vein and umbilical blood samples were obtained simultaneously. They were assayed by specific radioimmunoassay. Cord blood gases were obtained and compared with those from a control group of women undergoing elective cesarean section.nnnRESULTSnThe mean (+/- SD) maternal uterine vein concentration was 331.9 +/- 42.9 ng/ml, compared with 42 +/- 13 ng/ml in the umbilical vein (p < 0.05). The mean maternal/fetal was 12 +/- 0.03, which was not affected by the length of infusion. There was no significant difference in the hematocrit drop between the cesarean delivery groups: 5.9 +/- 0.4 for the control group versus 5.8 +/- 1.1 for the atosiban group (p > 0.1). The mean cord pH was 7.27 for the atosiban group versus 7.27 for the control group (n = 141) (p > 0.1). One year follow-up of the infants (n = 7) was normal.nnnCONCLUSIONSnOur results show minimal placental transfer of atosiban. Drug levels did not increase with longer infusions, and no effect was seen on umbilical cord gases. Administration of atosiban even at high doses up to the time of delivery did not increase maternal blood loss at cesarean section.

Estrogen effects on plasma volume, arterial blood pressure, interstitial space, plasma proteins, and blood viscosity in sheep

In adult castrated ewes the infusion of 17 beta-estradiol for 3 weeks was associated with a 12% increase in body weight, a 20% increase in whole blood volume (mainly due to a 27% increase of plasma volume), a 13% decrease in mean arterial blood pressure, and a 40% increase in heart rate. The change in plasma volume correlated with the change in estradiol concentration (r = 0.72). Most of the fluid was retained in the interstitial space, as represented by a 6 kg weight gain, 10% of which was in the intravascular compartment. Whole blood and plasma viscosity increased 16% and 21%, respectively, thus reversing some of the blood volume effects toward a hyperdynamic cardiovascular state. We conclude that many of the cardiovascular and hematologic changes with estrogen administration are similar to the changes observed during pregnancy, with the proposed requirement of decrease in mean arterial blood pressure as a condition for blood volume expansion.

Is there a need for digital examination in patients with spontaneous rupture of the membranes

A prospective comparison between digital and visual speculum examination was made in 133 pregnant patients. The coefficient correlation between the two examinations of effacement and dilation of the cervix was 0.74. The present results suggest that cervical evaluation by means of speculum examination in the assessment of pregnant patients with spontaneous rupture of membranes are adequate.

Estrogen, progesterone, prolactin, prostaglandin E2, prostaglandin F2α, 13,14-dihydro-15-keto-prostaglandin F2α, and 6-keto-prostaglandin F1α gradients across the uterus in women in labor and not in labor

Before or during labor in humans, changes in peripheral levels of estrogen and progesterone are not evident. Local alterations of estrogen, progesterone, and prolactin concentrations may be present and be accompanied by prostaglandin changes. The purpose of this study was to investigate the differences in concentrations of these hormones across the uterus and to evaluate their interrelationships in patients at term gestation with and without labor. Blood samples were obtained from a radial artery and a uterine vein in 22 women without and in 10 with labor. The difference between levels in the two blood vessels was designated as the gradient. Neither levels nor gradients were different between the two groups for estrone, estradiol, estriol, progesterone, or prolactin. The plasma levels of prostaglandin F 2α , 13,14-dihydro-15-keto-prostaglandin F 2α , and prostaglandin E 2 were significantly increased in labor. Prostacyclin levels, as indicated by the 6-keto-prostagland in F 1α metabolite, were not altered. The gradients for prostaglandin F 2α and E 2 were significantly increased in labor. The results of the study also suggested that, in gestation at term, serum prolactin is produced mainly by the pituitary and that estrone may originate from peripheral conversion of estradiol. We conclude that in humans prostaglandin gradients of the E and F groups are increased in labor. These increases are not associated with changes in sex steroids or prolactin. Prostacyclin metabolite gradients also appear not to be altered in labor, suggesting that some prostaglandins are selectively increased in early labor either by enhanced production or decreased metabolism or both.

Endothelin-1 potentiates the in vitro contractile response of pregnant human myometrium to oxytocin

OBJECTIVEnThis study was designed to test the hypothesis that endothelin-1 pretreatment of human myometrium at subcontractile doses in vitro will enhance the contractile response to oxytocin.nnnSTUDY DESIGNnIn vitro contractile oxytocin dose-response curves were generated by use of myometrial strips collected from nonpregnant women (n = 7), pregnant patients at elective cesarean section (n = 7), and patients in active labor (n = 7) in the presence or absence of 10(-9) mol/L endothelin-1. Contractile responses were analyzed by on-line computer, and data were normalized to the maximum response to potassium.nnnRESULTSnPretreatment with endothelin-1 significantly increased the maximal contractile response of pregnant myometrium (p < 0.01 compared with control). In marked contrast myometrium from nonpregnant patients was unaffected by endothelin-1 pretreatment. Values for the two-point discrimination and Hill coefficient were not different among the treatment groups.nnnCONCLUSIONnEndothelin-1 potentiates the oxytocin response of myometrium from pregnant but not nonpregnant women. We speculate that a high circulating level of a uterotonin-like oxytocin may not be necessary to initiate labor. The synergistic interaction between different uterotonins may be sufficient.

Acute intrauterine hypoxia increases amniotic fluid prostaglandin F metabolites in the pregnant sheep

OBJECTIVEnAmniotic fluid infection promotes cytokine release, prostaglandin production, and premature labor. In several tissues local hypoxia also activates the secretion of cytokines. Many patients initially seen in premature labor carry small-for-gestational-age fetuses, a condition associated with intrauterine hypoxia. The purpose of our study was to determine whether a reduction in placental blood flow and subsequent acute hypoxia affects prostaglandin secretion by the placenta.nnnSTUDY DESIGNnWe chronically catheterized six pregnant sheep at 120 days of gestation. We placed catheters in the maternal and fetal femoral arteries and in the amniotic fluid cavity. A flow probe and snare were placed around the common uterine artery.nnnRESULTSnA 30-minute uterine circulation occlusion of 30% of its control value produced an increase in prostaglandin F metabolite from 790 +/- 157 to 944 +/- 184 pg/ml within 10 minutes (p < 0.01). Additional uterine blood flow reduction to 60% of control increased the amniotic fluid prostaglandin F metabolites concentration to 894 +/- 202 (p < 0.05, analysis of variance). No increase in mean intrauterine pressure was detected (p > 0.1).nnnCONCLUSIONSnWe speculate that the prostaglandin increase in amniotic fluid in response to intrauterine hypoxia could eventually lead to premature labor. Whether the increase in prostaglandins is mediated by changes in cytokines is unknown at the present time.

Is a decrease in plasma oncotic pressure enough to explain the edema of pregnancy

The balance of fluid across capillaries is given by the Starling equation. Because the plasma protein concentration (one of its components) is decreased in pregnancy, we decided to explore the question as to whether hypoproteinemia with intact protein mass (produced by blood volume expansion) or hypoproteinemia with decreased total protein mass (produced by removal of circulating proteins) alters the oncotic pressure differences across capillaries. We calculated the oncotic pressure difference obtained in seven nonpregnant ewes during periods of normoproteinemia and hypoproteinemia; the influence of fluid infusion under both conditions was also observed. There was an increase in the oncotic pressure difference across the capillary wall during hypoproteinemia produced by a decrease in the total protein mass (p less than 0.01); however, the response to hypoproteinemia produced by fluid infusion was similar (p greater than 0.1). The venous pressure (used as an index of interstitial fluid pressure changes) did not differ in either hypoproteinemia or fluid infusion. Capillary permeability was decreased during hypoproteinemia, as evidenced by a higher lymph/protein ratio of labeled albumin during the control period (p less than 0.05). In conclusion, during a state of decreased plasma protein concentration similar to that of pregnancy, the difference in the oncotic pressure and hydrostatic pressure forces acting to prevent transfer of fluid to the interstitium is increased. Therefore other factors that influence fluid transfer across the capillaries must be investigated to explain the edema of pregnancy.

An unusual presentation of a case of staphylococcal pericarditis during pregnancy

Abstract A case of a pregnant, drug-addicted patient with a pyogenic pericarditis without the systemic infectious manifestations is described.

Long-term vascular volume expansion maintains elevated thoracic duct lymph flow

OBJECTIVEnTo investigate the mechanisms responsible for edema seen during pregnancy, we tested whether lymph vessels are able to pump high volumes over long periods of time.nnnSTUDY DESIGNnIn six chronically catheterized nonpregnant ewes, we examined left thoracic duct lymph flow rate and fluid balance responses to the administration of a balanced isotonic solution at a rate of 1 L/hr for 20 hours. Because estrogen administration decreases lymphatic contractility against outflow pressure, we also administered conjugated estrogens (Premarin) during the last 3 hours of the fluid infusion (experimental time 17 to 20 hours).nnnRESULTSnAfter volume loading for 16 hours, the mean +/- SEM lymph flow rate, blood volume, and arterial pressure rose 100% +/- 26%, 20% +/- 2.3%, and 16% +/- 8.1%, respectively. Vascular compliance decreased significantly and, as evidenced by a lack of body weight changes, interstitial fluid volume failed to change (p < 0.05, analysis of variance). The transcapillary oncotic pressure difference increased by 2 mm Hg; venous pressure increased by 5.2 mm Hg. These data suggest that transcapillary forces favored fluid movement into the interstitium. Lymph flow rate remains elevated after blood volume expansion to a level similar to that described during pregnancy in sheep. A transient decrease in urinary output (approximately 20%) occurred with no changes in lymph flow rate, arterial pressure, or blood volume.nnnCONCLUSIONnLymph flow rate is able to compensate for the increased capillary filtration observed during prolonged blood volume expansion.

Lymph flow rate response to angiotensin II is decreased in pregnant sheep

Pregnancy in humans is associated with a number of physiologic changes including interstitial fluid retention (edema) and a decrease in the systemic vascular response to infused angiotensin II. In nonpregnant sheep angiotensin II increases the lymph flow rate by what appears to be a direct effect on the lymphatic vessels. The purpose of this study was to test the hypothesis that during pregnancy the lymph flow rate response to angiotensin II infusion is decreased in relation to that of the nonpregnant state. We speculate that a decrease in lymph flow may explain the interstitial fluid retention observed during human pregnancy. In nine nonpregnant and five pregnant chronically catheterized ewes, we infused angiotensin II at rates of 0.1, 10, and 1000 ng/kg/min during a 5-minute period, with intervals of at least 15 minutes between doses. At the highest angiotensin II dose, peak lymph flow rate increased 286% in pregnant ewes compared with an increase of 344% in the nonpregnant sheep (p less than 0.05). No changes occurred in the intravascular volume, plasma or lymph protein concentration, or venous pressure. The arterial pressure responses to angiotensin II were decreased in pregnant sheep (p less than 0.05). These results are compatible with a model for fluid retention in pregnancy in which a decreased lymph flow rate plays a significant role in interstitial fluid retention.