Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis

The coronary circulation is the major determinant of myocardial oxygen balance which in turn is necessary for adequate cardiac function under a variety of conditions. Experiments in the fetal lamb suggest short-term functional coronary autoregulation in response to increase in afterload and acute hypoxemia. Long-term, acute-on-chronic hypoxemia is associated with a marked increase of maximal myocardial flow reserve suggesting coronary vascular angio-neogenesis during the period of chronic hypoxemia. In the human fetus, flow velocity waveforms from the coronary arteries may be obtained by color-coded and pulsed wave Doppler sonography in normally developed fetuses from 31 weeks of gestation onwards under favorable imaging conditions. Coronary blood flow may also be visualized in selected fetuses with intrauterine growth restriction, absent or reversed end-diastolic flow in the umbilical artery, cephalization of blood flow and abnormal flow patterns in the precordial veins and the umbilical vein. In these fetuses visualization of coronary blood flow may be possible as early as 26 weeks gestation and is consistently associated with a significant increase in the peak velocity index for veins in the ductus venosus. In this circulatory state, visualization of coronary blood flow is suddenly very easy. This "visualization threshold" may be a sign of maximal increase in coronary blood flow in an attempt to "spare" the fetal heart of hypoxemia. Although highly operator dependent, demonstration of coronary blood flow in intrauterine growth restriction identifies fetuses at high risk for intrauterine fetal death and postpartum circulatory failure.     

Cardiotocogram compared to Doppler investigation of the fetal circulation in the premature growth-retarded fetus: longitudinal observations

It was our objective to compare computerized fetal heart rate analysis with blood flow velocity waveform analysis of the arterial and venous fetal circulation in intrauterine growth retardation. We report five illustrative cases with longitudinal observations of fetal Doppler findings and fetal heart rate between 23 and 32 weeks of gestation. Blood flow waveforms were recorded from the umbilical artery, middle cerebral artery, descending aorta, ductus venosus and inferior vena cava. Fetal heart rate was analyzed by a computer system according to the Dawes-Redman criteria. The time sequence of deterioration is described individually for each fetus. An abrupt increase in pulsatility of ductus venosus waveforms with loss of forward flow velocity during atrial contraction preceded abnormally low short-term variation of fetal heart rate. With advanced gestational age and concomitant maternal disease, we observed severe alterations of flow velocity waveforms within 12 h of normal Doppler measurements, which is in contrast to findings in the second trimester, in which severely abnormal venous waveforms were observed over a period of several weeks before intrauterine death occurred. In a fetus with terminally low short-term variation, normal venous waveforms indicated fetal well-being despite an abnormal cardiotocogram (CTG). We challenge the current concept that the CTG is the best available parameter to determine the optimal time for elective delivery of premature growth-retarded fetuses. Deterioration in ductus venosus blood flow seems to precede an abnormal CTG and thus heralds the need for delivery.     

Changes of venous blood flow velocity waveforms in fetuses with supraventricular tachycardia

Studies in the fetal lamb have shown that atrial pacing beyond a rate of 300-320 beats/min may be associated with dramatic changes of venous blood velocity waveforms, an increase of venous pressure by up to 75%, hydrops, polyhydramnios and placental edema. The aim of our study was to determine the 'critical' heart rate frequency in the human fetus. In 11 fetuses (five with and six without hydrops) with supraventricular tachycardia, pulsed wave Doppler analysis of flow velocity waveforms of the inferior vena cava, the ductus venosus and the left hepatic vein were performed before and after drug treatment. In ten cases cardioversion was achieved by in utero antiarrhythmic drug therapy; in one case treated with digoxin and flecainide the supraventricular tachycardia was decreased to 160-190 beats/min with disappearance of hydrops. Before intrauterine treatment of supraventricular tachycardia, pulsatile reversal of blood flow in the inferior vena cava, ductus venosus and left hepatic vein was visible, with monophasic forward flow during systole and reversed flow during diastole in ten of 11 fetuses. One fetus with supraventricular tachycardia of 195 beats/min showed a normal biphasic forward flow pattern. During drug-induced sinus rhythm, a normal biphasic forward venous blood flow pattern was shown in all ten cases. In five cases pulsatile reversal was demonstrated during a drug-induced reduction of the heart rate from 280 to 210 beats/min and a normal biphasic forward flow velocity waveform appeared during supraventricular tachycardia below 210 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doppler echocardiographic assessment of fetal blood flow redistribution during maternal hyperoxygenation

In a retrospective analysis of the standard protocols for fetal echocardiographic examination, 27 fetuses (mean gestational age 29 +/- 5.4 weeks) with ascites were evaluated. Fetal cardiomegaly (increased heart area/chest area ratio), the presence or absence of atrioventricular valve regurgitation, inferior vena cava and ductus venosus Doppler flow velocity and umbilical vein pulsation were evaluated quantitatively in a group of survivors and non-survivors. A statistically significant difference between the two groups was found for the presence of atrioventricular valve regurgitation (p = 0.003), and for cardiomegaly (p = 0.009). There was no statistical difference for the presence of abnormal venous flow and umbilical pulsation (p > 0.05). Abnormal venous Doppler flow velocities in the inferior vena cava and ductus venosus were observed more frequently than umbilical vein pulsation. The mean heart area/chest area ratios in the group of survivors and in the group of non-survivors were 0.34 +/- 0.09 and 0.48 +/- 0.08, respectively (p < 0.001). The mean gestational ages at the time of diagnosis of ascites in the groups of survivors and non-survivors were 33 +/- 3.3 weeks and 28 +/- 5.1 weeks, respectively (p < 0.05); the mean gestational ages at the time of delivery were 35.6 +/- 2.3 weeks and 33.3 +/- 4.9 weeks, respectively (p = 0.33). In terms of different echocardiographic features as well as the gestational age of the unborn patient with ascites, there is apparently no single indicator of a poor prognosis. Our results suggest that the prognosis is usually poor in a fetus with ascites, when cardiomegaly is detected, as well as the presence of tricuspid and mitral valve regurgitation. This is regardless of the type of venous flow and regardless of the etiology of the ascites.     

Doppler-velocity waveforms in ductus venosus in normal and small-for-gestational-age fetuses

OBJECTIVE: To investigate blood-flow patterns in ductus venosus in growth-retarded fetuses. METHODS: Reference ranges of ductus venosus flow velocities were constructed from a cross-sectional study of 179 normal fetuses between 16 to 38 weeks' gestation. and the ductus venosus flow-velocity waveforms in 11 small-for-gestational-age (SGA) fetuses were compared with normal patterns. RESULTS: Of 179 pregnant women who were possible subjects, 175 were employed for the analysis, and ductus venosus flow-velocity waveforms were obtained in 197 out of 211 examinations (success rate = 93.4%). The peak forward velocities during (a) ventricular systoles, (b) the lowest forward velocities during atrial contractions, and (c) the time-averaged velocities all linearly increased as gestational ages increased [respectively: (a) slope, 1.135; constant, 31.720; (b) slope, 1.154; constant, 1.557; (c) slope, 1.240; constant, 19.386]. Peak forward velocities during ventricular systoles and time-averaged velocities in the SGA group did not differ from those of the normal group. Three SGA fetuses with abnormal flow in the umbilical artery showed a marked reduction of the lowest velocities during atrial contractions in the ductus venosus, and two of them showed no forward velocity at all. CONCLUSION: The Doppler-velocity waveforms of ductus venosus showed a marked reduction of the end diastolic flow, especially in SGA fetuses with abnormal umbilical artery flows.     

Characteristics of a low affinity passive Ca2+ influx component in rat parotid gland basolateral plasma membrane vesicles

Prenatal detection of intrauterine closure of the ductus arteriosus unrelated to maternal administration of non-steroidal anti-inflammatory drugs or glucocorticoids made it possible to study the circulation in this condition in the human fetus and newborn by pre- and postnatal echocardiography and neonatal cardiac catheterization. At 38 weeks, the fetus presented intrauterine ductal closure associated with right ventricular dilatation and marked hypertrophy of the right ventricle and the interventricular septum, as well as severely diminished right ventricular fractional shortening and diminished pulmonary blood flow. Blood flow redistribution was characterized by reduced blood flow through the right heart and increased right-to-left shunting across the dilated foramen ovale. Pathological Doppler waveforms of the inferior vena cava and the ductus venosus were found, although the cardiotocogram was normal. Following unsuccessful induction of labour a Caesarean section was performed. Postnatal echocardiography confirmed the prenatal findings. Cardiac catheterization, performed because of persistent dependence on additional oxygen administration, revealed increased pulmonary vascular resistance, reduced pulmonary blood flow, and prolonged right-to-left shunt across the foramen ovale. Reduced peripheral pulmonary artery diameters were shown angiographically. Follow-up examinations revealed regression of right ventricular hypertrophy and recovery of right ventricular and pulmonary function. The findings confirm results from haemodynamic studies in animal experiments.     

Closure of the ductus venosus in premature infants: findings on real-time gray-scale, color-flow Doppler, and duplex Doppler sonography

OBJECTIVE: Our objective was to use gray-scale, color-flow, and duplex Doppler sonography to study the anatomy, flow pattern, and time of closure of the ductus venosus in healthy premature infants. SUBJECTS AND METHODS: We prospectively examined the ductus venosus in 130 premature infants whom we divided into two groups: Group I comprised 27 neonates of gestational age 28-32 weeks, and group II comprised 103 neonates of gestational age 33-36 weeks. Neonates who had undergone umbilical vessel manipulation were excluded from the study. All examinations included gray-scale, color-flow, and duplex Doppler sonography. Patency, length, color flow, and Doppler characteristics of the ductus venosus were recorded. Neonates were examined 1-2 days after birth, 6-7 days after birth, and subsequently every 3-4 days until ductus closure was observed. The time of closure of the ductus for the two groups was compared using the chi-square test. RESULTS: The ductus venosus was patent during the initial examination in 128 of the 130 neonates. Doppler waveform was venous with little variation in velocity. Ductus length slightly exceeded 1 cm in both groups. We found a statistically significant difference in the percentage of infants having a patent ductus venosus after the initial examination: At 1 week after birth, ductus patency was shown in 85% of the infants in group I and in 56% of the infants in group II; at 2 weeks, the respective percentages were 42% and 14%; and at 3 weeks, 27% and 0%. CONCLUSION: The ductus venosus is patent 1-2 days after birth in virtually all premature infants. From 6 days after birth and onward, a significantly greater percentage of smaller premature infants (i.e., 28-32 weeks' gestational age) have a patent ductus venosus than do larger premature infants (i.e., 33-36 weeks' gestational age).     

The head-to-abdomen circumference ratio: a reappraisal

Our objective was to assess the clinical significance of the sonographically derived head-to-abdomen circumference ratio in small-for-gestational-age (SGA) fetuses. The head-to-abdomen ratio was determined in 134 singleton SGA fetuses without ultrasound evidence of malformations at 26-40 weeks' gestation. Data were collected regarding antenatal surveillance, umbilical artery Doppler velocimetry and neonatal outcome. In SGA fetuses, the head-to-abdomen ratio, adjusted for gestational age, had a normal frequency distribution, positively skewed with regard to fetuses with normal birth weight. An elevated head-to-abdomen ratio was found in 56 SGA fetuses (42%), and was associated with increased perinatal mortality (odds ratio 3.27; 95% confidence internal 1.04-9.34), lower birth weight (1533 +/- 635 g vs. 2022 +/- 655 g, p < 0.0001) and lower gestational age at delivery (34 +/- 3.6 weeks vs. 36.3 +/- 3.6 weeks, p < 0.005). However, logistic regression revealed that the most powerful antenatal determinants of pregnancy outcome were Doppler velocimetry of the umbilical artery, followed by biophysical profile, while no independent correlation was found with the head-to-abdomen ratio. The existence of two distinct categories of SGA fetuses, 'symmetric' and 'asymmetric', remains uncertain. An elevated head-to-abdomen ratio is an adverse risk factor for pregnancy outcome. However, this parameter has no clearcut clinical value when umbilical artery Doppler velocimetry and biophysical antenatal testing are available.     

Cardiac flow after fetal blood sampling in normally grown and growth-retarded fetuses

The objective of this study was to evaluate the effect of fetal blood sampling on cardiac flow velocity waveforms. Flow velocity waveforms were measured from the ascending aorta and pulmonary artery immediately before and after fetal blood sampling in 29 normally grown and 12 growth-retarded fetuses. The latter group was characterized by abnormal Doppler indices in the umbilical artery and middle cerebral artery suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. The flow velocity parameters studied were the peak velocity, the time to peak velocity, and the left and right cardiac output and their ratio. In normally grown fetuses, the peak velocity and right and left cardiac output values increased significantly after fetal blood sampling, while no significant changes were observed in the other indices considered. The gestational age at the time of the procedure was positively related to the amplitude of these changes. In growth-retarded fetuses, fetal blood sampling did not induce any significant increase in cardiac output or peak velocities, while in more than 50 per cent of the fetuses these Doppler indices decreased. The amplitude of the decrease was significantly related to the severity of acidosis in the umbilical vein. In conclusion, the cardiac haemodynamic response to fetal blood sampling differs between normally grown and growth-retarded fetuses. This difference may explain the higher rate of complications occurring in the latter group of fetuses after blood sampling.     

Experimentally contaminated reabsorbable meshes: their evolution in abdominal wall defects

The effect of maternal hyperglycemia on fetal regional circulation in appropriate for gestational age and small for gestational age fetuses was evaluated. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on 15 appropriate for gestational age and 19 small for gestational age fetuses, ranging from 33 to 40 weeks' gestation before, 60 minutes, and 120 minutes after a maternal 75 g glucose load. The pulsatility index (PI) was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery, and umbilical artery. Simultaneously, maternal plasma glucose concentration was measured. Baseline PI value (1.50 +/- 0.31) for middle cerebral artery in small for gestational age fetuses was significantly lower than that (1.89 +/- 0.37) in appropriate for gestational age fetuses (p < 0.05); however, there were no significant differences in baseline PI values for other arteries in both groups. In appropriate for gestational age fetuses, the mean PI decreased from 1.89 +/- 0.37 to 1.47 +/- 0.33 at 60 minutes, and to 1.55 +/- 0.32 at 120 minutes (p < 0.05), but no changes were found in the other arteries. In small for gestational age fetuses, there was no significant change in PI value for each artery before and after maternal glucose load. Maternal hyperglycemia induces a significant decrease in cerebrovascular resistance in appropriate for gestational age fetuses but not in small for gestational age fetuses. These results provide a foundation for evaluating the effect of maternal hyperglycemia on fetal regional circulation.     

Effects of morphine and halothane anesthesia on coronary blood flow

This study was undertaken to determine the relative effects of morphine and halothane anesthesia on coronary blood flow. Right heart bypass was instituted in 20 dogs by draining the vena cava blood into a cardiotomy reservoir and returning it to the main pulmonary artery. Coronary sinus drainage was measured by a right ventricular cannula. Group I (10 dogs) was sequentially given 0.5, 1, 1.5, 2.0, and 2.5% halothane. Group II (10 dogs) was given 1, 2, 3, 4, and 5 mg per kilogram of morphine intravenously. Arterial pressure, coronary sinus blood flow, cardiac output, arterial pH, PCO2, and PO2 were determined and repeated at each dose level of anesthesia and compared to the control values. Morphine significantly increased coronary flow at 3, 4, and 5 mg/kg without pressure adjustment and at 2 mg/kg after pressure adjustment. Coronary flow with halothane was unchanged from control values except for a decrease at 2.5%. Coronary flow was significantly greater with 3, 4, and 5 mg/kg of morphine than with 1.0 and 1.5% halothane.     

In utero ultrasonographic diagnosis of an aberrant umbilical vein associated with fetal hepatic hyperechogenicity

Intra-hepatic abnormalities of the fetal umbilical venous system are poorly documented and clinically not well understood. A case of routine ultrasound examination at 23 weeks' gestation demonstrating foci of hepatic hyperechogenicity and cardiomegaly is presented. Colour Doppler detected absence of flow in the ductus venosus and markedly increased blood flow through an aberrant channel connecting the umbilical vein with the right atrium. The pregnancy was terminated and anomalous venous drainage of the umbilical vein into an enlarged hepatic vein was found, as well as hepatic congestion and focal hepatic necrosis and calcifications. Incidental findings of fetal hepatic hyperechogenicities require colour Doppler investigation of the intra- and extra-hepatic venous systems. We propose that a thrombo-embolic mechanism may be involved in the pathogenesis of these lesions.     

Umbilical arterial S-nitrosothiols in stressed newborns: role in perinatal circulatory transition

S-Nitrosothiols are potent endogenous vasodilators recently found to be in greater concentrations in fetal umbilical venous than arterial blood. We hypothesized that neonatal increases in SNOs may be involved in the normal human perinatal circulatory transition. Paired human umbilical artery and vein plasma samples were collected after birth. S-Nitrosothiol concentrations were measured as NO after photolysis--and NO3- after reduction in vanadium chloride--by chemiluminescence. Normal umbilical arterial serum SNO levels were nearly twice those of matched venous samples but were low in infants who did not transition normally to neonatal circulation. There was no difference in the concentration of NO3- between the normal and depressed infants. The parallel failure of some fetuses to switch both to a normal arteriovenous SNO relationship and a normal clinical post-partum state suggests that SNOs may be involved in the perinatal circulatory transition.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age < or =32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in "healthy" (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in "unhealthy" (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2 h of phototherapy prior to its discontinuation.     

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.     

Role of nitric oxide in coronary arterial vasomotion and the influence of coronary atherosclerosis and its risks

Healthy coronary vascular endothelium releases nitric oxide to modulate resting and dynamic coronary arterial tone. We studied the impact of atherosclerosis and/or its risks on endothelial nitric oxide release in response to metabolic stimuli by evaluating coronary vasomotor responses to atrial pacing before and after the inhibition of nitric oxide production by intracoronary NG-monomethyl-L-arginine (L-NMMA) (20 micromol/min) infusion. The study includes 34 patients (15 with coronary disease, 11 with normal coronary arteries and > or =1 risk factor, and 8 with normal coronary arteries and no risks). Coronary blood flow was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter. L-NMMA infusion reduced coronary blood flow by 18 +/- 16% and coronary diameter by 10 +/- 9%. Responses were identical in all subgroups. Coronary blood flow responses to pacing were similar in all subgroups and were unaffected by L-NMMA (11 +/- 11 vs 13 +/- 9 ml/min; p = 0.26). Epicardial coronary vasodilation to control pacing occurred in patients with normal coronary arteries with (4.0 +/- 5.2%, p = 0.01) or without (8.0 +/- 5.2%, p = 0.03) risks, but not in patients with coronary disease (2.8 +/- 5.9%). L-NMMA abolished pacing-induced epicardial vasodilation in patients without coronary artery disease, producing a 1.8 +/- 5.1% response, which was similar in all subgroups. We conclude that microvascular responses to rapid atrial pacing are not mediated by nitric oxide. Flow-mediated epicardial coronary arterial responses may be nitric oxide dependent.     

Value of intracoronary ultrasound and Doppler in the differentiation of angiographically normal coronary arteries: a prospective study in patients with angina pectoris

BACKGROUND: A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time. METHODS AND RESULTS: In forty-four patients with suspected coronary artery disease and normal coronary angiograms, intracoronary ultrasound and intracoronary Doppler were performed in the left anterior descending and left main coronary arteries. Coronary flow reserve was obtained by calculating the ratio of the maximal coronary flow mean velocity after the intracoronary administration of 10 mg papaverine to the coronary flow mean velocity at rest. Of 44 patients, 16 (36%) (group I) were found to have normal coronary morphology by intracoronary ultrasound and normal (> 3.0) coronary flow reserve (5.3 +/- 1.8). In seven patients (16%) (group II) there were normal intracoronary ultrasonic findings but a reduced coronary flow reserve (2.1 +/- 0.4). Plaque formation was found in a total of 21 (48%) of the 44 patients; mean plaque sizes were 3.6 +/- 1.6 mm2 for those in group III (normal coronary flow reserve) and 5.0 +/- 2.3 mm2 for those in group IV (reduced coronary flow reserve). Vessel area in both of these groups (16.3 +/- 8.0 mm2 and 19.2 +/- 6.1 mm2) was significantly larger than that of group I (14.6 +/- 5.7 mm2, P < 0.01). Plaque calcification was found in 25% of those in group III and 44% of those in group IV. Thus, only 36% of the patients with normal angiograms were true normal, 48% exhibited early stage of coronary atherosclerosis, and the other 16% might be considered as syndrome X. CONCLUSION: Intracoronary ultrasound and Doppler can be used to differentiate further heart disease in patients with normal coronary angiograms. Only a minority were true normal. Early signs of atherosclerosis cannot be detected by coronary angiography. This may have important therapeutic and prognostic implications.     

Umbilical artery blood flow velocity in pregnancies complicated by systemic lupus erythematosus

PURPOSE: We evaluated the role of umbilical artery Doppler velocimetry in the surveillance of pregnancies complicated by systemic lupus erythematosus (SLE). METHODS: We retrospectively studied 56 women with SLE whose pregnancies were managed at our perinatal center between 1988 and 1995. RESULTS: Absent or reversed end-diastolic flow velocity was detected in 6 (11%) of 56 patients. This sub-group of patients had an increased risk of pre-eclampsia, intrauterine growth restriction, cesarean section, and preterm delivery. CONCLUSIONS: A high incidence (11%) of abnormal umbilical artery waveforms was detected. This finding was associated with an increased risk of maternal and fetal complications.     

Differential distribution of endothelin receptor subtypes in placentae from normal and growth-restricted pregnancies

The endothelins (ETs) are potent vasoconstrictor peptides that bind to two distinct receptors, ETA and ETB. This study compares the localization of ETA and ETB receptors in placentae complicated by intrauterine growth retardation (IUGR) and abnormal umbilical Doppler waveform, gestationally matched controls, fetuses that were small for gestational age (SGA), and normal term placentae. Quantitative autoradiography was performed using ETA and ETB subtype-selective ligands. Both ETA and ETB receptors were expressed in the human placenta. Gestational and fetal size effects on the receptor density within stem villi were found, but no effect of abnormal placental blood flow could be demonstrated. A distinct spatial distribution of receptor subtypes within the placenta was observed. Smooth muscle cells expressed both receptors with ETA expression predominant in the proximal regions of the villous tree and ETB abundant in the periphery and decidua. Both receptors were also expressed at lower density on paravascular stromal cells in stem villi. Although these data do not demonstrate aberrant localization of ET receptors in IUGR and SGA placentae, the spatially distinct distribution of ET receptors in the human placenta suggests that ETs play a role in modulation of placental blood flow.     

Reversed end-diastolic umbilical flow in a first-trimester fetus with congenital heart disease

Reversed end-diastolic umbilical artery velocities and a reduced chorionic sac were first seen at 10 weeks in a pregnancy subsequently showing a normal male karyotype on chorionic villi. Four weeks later Doppler studies demonstrated normal umbilical artery waveforms. At 20 weeks, ultrasound examination of the fetus revealed a mild pericardic effusion, hypoplastic righ heart with hypertrophic myocardium and a single umbilical artery, suggesting pulmonary atresia. After neonatal death, pathological studies confirmed pulmonary atresia. This case suggests that reversed end-diastolic umbilical flow in the first trimester may identify a subgroup of fetuses with a lethal abnormality (heart defect, severe intra-uterine retardation, aneuploidy or others).