The flow pattern in fetal central veins is of diagnostic significance in Obstetrics. Yet the pressure drop, and the pressure pulses which drive flow have not been measured directly and been related to flow in the isthmus of the ductus venosus and other central veins. In eight acutely anaesthetized (isofluran/N2O/O2) fetal sheep (median gestational age 122 days, term 145 days), a 3F tip pressure transducer (TP) was inserted from the external jugular vein into the umbilical vein (UV) under ultrasound B-scan guidance (Acuson Aspen®). Ultrasound Doppler flow velocities, TP position and intravenous pressures were recorded in the UV, ductus venosus (DV) and inferior vena cava (IVC) while the TP was withdrawn in steps. A fluid filled catheter was inserted into the right carotid artery to measure arterial pressure pulses and blood gas values. The time difference between the onset of arterial pressure pulses and defined points of the central venous pressure curves at the various locations was determined. Flow was steady in the UV but small pressure fluctuations (< 0.4 mm Hg) could be detected which did not depend on arterial oxygen partial pressure. Time-averaged pressure dropped 1.9 (0.5–3.3) mm Hg (mean, 95% confidence interval) across the DV isthmus. Pressure pulses increased from 1.7 (1.2–2.1) mm Hg in the DV to 3.9 (1.8–6.0) mm Hg in the IVC. The pressure wave from the heart arrived later (0.053 sec [0.025–0.080]) in the isthmus of the DV than in the diaphragmatic IVC indicating a wave velocity of approximately 1.1 m sec-1. At all locations, pressures and flow velocities were inversely related. The results confirm pressure estimates based on mathematical modeling. The experimental model is suitable to study pathopyhsiological mechanisms which affect fetal central venous flow patterns.

The pressure drop and pressure pulses in the isthmus of the ductus venosus (DV) in fetal sheep have not been measured directly and related to flow. In eight acutely anesthetized fetal sheep, a 3-Fr tip pressure transducer (TP) was inserted from the external jugular into the umbilical vein (UV). Ultrasound Doppler flow velocities, TP position, and intravenous pressures were recorded in the UV, DV, and inferior vena cava (VC) while the TP was withdrawn. Flow was steady in the UV, but small pressure fluctuations (<0.4 mmHg) could be detected. Time-averaged pressure dropped 1.9 mmHg (mean; 0.5-3.3 mmHg 95% confidence interval) across the DV isthmus. Pressure pulses increased from 1.7 mmHg (mean; 1.2-2.1 mmHg 95% confidence interval) in the DV to 3.9 mmHg (mean; 1.8-6.0 mmHg 95% confidence interval) in the inferior VC. The pressure wave from the heart arrived later [0.053 s (mean; 0.025-0.080 s 95% confidence interval)] in the isthmus of the DV than in the diaphragmatic inferior VC, indicating a wave velocity of approximately 1.1 m/s. At all locations, pressures and flow velocities were inversely related.

A 17-year-old primigravida was referred at 31 + 6 weeks' gestation because of a supraumbilical fetal midline defect, thoracoabdominal ectopia cordis, and sternal aplasia. Fetal echocardiography showed a double-outlet right ventricle with pulmonary artery stenosis and a ventricular septal defect. Karyotyping was declined. After premature rupture of the membranes at 36+5 weeks' gestation a 3000-g male infant was delivered by cesarean section. The Apgar scores were 3/3 and the arterial cord blood pH was 7.26. Tissue coverage of the supraumbilical defect and the omphalocele was performed. Hemodynamic instability precluded primary replacement of the heart into the thorax. To relieve pressure a corset was fashioned for the thorax. The double-outlet right ventricle was corrected at 5 months. At 17 months the child is alive and stable. Replacement of the extrathoracic heart is planned at a later date.

Wir berichten über eine 17-jährige Patientin, die in der 31 + 6 SSW bei supraumbilikalem Mittelliniendefekt mit thorakoabdominaler Ectopia cordis und Sternumaplasie des männlichen Feten zur weiteren pränatalen Betreuung überwiesen wurde. Echokardiographisch fanden sich ein Double Outlet Right Ventricle (DORV) mit Pulmonalstenose und Ventrikelseptumdefekt. Eine invasive Diagnostik zur Karyotypisierung wurde nicht gewünscht. In der 36 + 5 SSW wurde bei vorzeitigem Blasensprung eine sekundäre Sectio caesarea durchgeführt. Das männliche Neugeborene (Gewicht 3000 g, Apgar 3/3/intubiert, Nabelschnur pH-Wert 7,26) wurde zur weiteren Versorgung auf die neonatologische Intensivstation verlegt. Im weiteren Verlauf erfolgte nach erfolgreicher Stabilisierung eine plastische Deckung des Herzens und der Omphalozele. Eine initiale Rückverlegung des Herzens in die Thoraxhöhle war aus hämodynamischen Gründen nicht möglich. Ein thorakales Korsett wurde zur Druckentlastung angepasst. Im 5. Lebensmonat erfolgte die operative Korrektur des Double Outlet Right Ventricle. 17 Monate nach der Geburt lebt der Patient und ist stabil. Die Rückverlagerung des extrathorakal liegenden Herzens ist für einen späteren Zeitpunkt geplant.

Objective To assess the diagnostic power of the umbilical venous-arterial index (VAI) for the prediction of poor fetal outcome.Subjects and methods This was a retrospective, cross-sectional clinical study in which normalized umbilical vein blood volume flow rate (nUV) (mL/min/kg estimated body weight), umbilical artery pulsatility index (UAPI), the newly developed VAI (nUV/UAPI), and the uterine artery resistance index (UTRI) were determined in 85 fetuses once (17-41 gestational weeks) during pregnancy using standard ultrasound Doppler equipment. A risk score based on umbilical blood pH, 1-min Apgar score, birth weight, duration of gestation, type of respiratory support, and referral to the pediatric department was constructed, and fetuses were assigned to a control or a pathological group accordingly. Logistic regression and analysis of fitted receiver-operating characteristics curves were performed to evaluate the diagnostic power of nUV, UAPI, UTRI, and VAI.Results The incidence of compromised neonates was 17.6%. The area under the receiver-operating characteristics curve was larger for VAI than for UTRI or for UAPI (P < 0.002). At a cut-off value of 100 mL/min/kg, the sensitivity of VAI to predict poor neonatal outcome was 85% with a 15% false-positive rate.Conclusion Determination of the VAI has a greater diagnostic power to predict poor fetal outcome than the pulsatility index in the umbilical artery or the resistance index in the uterine artery.

The purpose of this study was to learn to what extent carotid collateral circulation is efficient in maintaining cephalic blood flow in the sheep fetus. Under halothane anaesthesia six fetal sheep at 124-135 days of gestation were instrumented with inflatable occluders around both common carotid arteries, an inductive flow probe around one external carotid artery, and arterial catheters to measure carotid sinus and aortic pressure. In acute experiments, the occluders were inflated on one side, or the other, or both sides simultaneously, while carotid blood flow, driving pressures and fetal heart rate were determined. Ipsi- and bilateral occlusion reduced carotid blood flow from about 42 ml/min to 10-0 ml/min and decreased sinus pressure from 39 mmHg to 29.1+/-2.9 (mean+/-s.d.) and 16.7+/-3.7 mmHg, respectively. Occlusion of the contralateral carotid artery increased ipsilateral carotid blood flow from 45+/-10 ml/min to 64+/-14 ml/min within 0.2 sec. Heart rate and aortic and sinus pressures did not change appreciably. Analysis of an analogue resistance network demonstrated that the observed carotid flow increases (less than twice normal) do not require changes of vascular resistances.It is concluded that the fetal sheep, as in the adult of many species, possesses an efficient carotid collateral system.

Unloading of baroreceptors by carotid occlusion does not increase heart rate in fetal sheep; Objectives: To test the hypothesis that in fetal sheep reduction of carotid sinus pressure by carotid occlusion increases heart rate. Study design: Fetal sheep (gestational age 121–132 days) were chronically instrumented with bilateral carotid occluders, catheters and electrodes (ECG) to measure systemic arterial and carotid sinus (CSP) blood pressures, and fetal heart rate. Results: Bilateral carotid occlusion (BCO) increased mean arterial blood pressure from 46±7 mm Hg to 53±8 mm Hg (mean±S.D.) while CSP decreased from 44±7 mm Hg to 17±7 mm Hg. Fetal heart rate fell during occlusion significantly from 186±34 bpm to 159±26 bpm (n=20 animals). Infusion of phenylephrine (8.5–20 μg min−1 kg−1) or methoxamine (60–200 μg min−1 kg−1) increased mean blood pressure from 44±6 to 61±9 mm Hg, and fetal heart rate decreased from 186±30 to 132±31 bpm (n=12). BCO increased systemic arterial pressure further to 70±11 mm Hg whereas carotid sinus pressure was reduced to 31±13 mm Hg. However, average heart rate did not increase significantly (136±28 bpm). Conclusion: We conclude that in contrast to adult animals, in fetal sheep carotid occlusion with subsequent unloading of baroreceptors does not increase heart rate even when the baroreflex had been activated by arterial hypertension. It seems likely that stimulation of carotid chemoreceptors prevents the expected baroreceptor mediated heart-rate response.

The influence of oxytocin (OXY), sulproston (SUL) and acetylsalicylic acid (ASA) on L-alanine- (ALA), D-glucose- (GLU) or water- (H(2)O) uptake (maternal side) in the isolated perfused guinea pig placenta was investigated. Uptake was measured with a single injection, paired tracer dilution method. 'T50' values were derived from venous concentration curves (extracellular marker) as the distance (sec) between two concentration values at 50 per cent of peak concentration. T50 values were regarded to reflect the change of flow distribution on the maternal side. On average, there was a significant apparent inhibition of GLU uptake (by 27.2 per cent from control values) by OXY as well as of ALA uptake by OXY (26. 0 per cent), by ASA (56.6 per cent), and by SUL (56.7 per cent). The respective mean T50 values decreased significantly in the above groups by 15.9 per cent, 18.7 per cent (ns), 42.2 per cent and 56.7 per cent. However, it was not possible to generate dose-response curves whereas significant correlations of uptake values with T50 values were found. There was no dose-response relationship between T50 values and OXY or ASA concentrations but decreased mean T50 values were found. For SUL a weak correlation of T50 and SUL concentration was found. The r -value of GLU uptake and T50 was 0.57, for H(2)O uptake this value was 0.70, for ALA uptake the r -values were 0.51 (OXY), 0.35 (SUL) and 0.31 (ASA). Correlation of uptake and concentrations were not significant. We conclude that the 'inhibitory' effects of OXY, ASA and probably SUL on placental transfer are unspecific and the consequence of flow shifts from the placental exchange area to the uterine muscle.

This study investigated systematically the diffusive transfer of water and glucose across the chorionic plate of the human placenta. Isolated sections of human term placentae were perfused at the fetal side (open loop) with modified Ringer's solution (n=31). An artificial amniotic compartment was created on top of the chorionic plate. 3H- and 14C-labelled tracer pairs were added (donor side) to the fetal perfusion fluid or to the 'amniotic' fluid. Transfer fractions (TF, ratio of acceptor side to donor side radioactivity) were calculated as percentages. TF of water and L-glucose from perfusion fluid into the 'amniotic' fluid were 3.9+/-0.5 per cent (mean+/-SEM) and 1.2+/-0.3 per cent after 60 min and significantly different (n=6). In each sample of the following experiments the transfer fraction of the D-hexose was larger than that of the L-isomer. At 60 min, the TF were 1.6+/-0.2 and 1.1+/-0.2 per cent (D-glucose/L-glucose; fetal to amniotic compartment, n=8), from amniotic compartment to fetal perfusate 0.6+/-0.1 and 0.4+/-0.1 per cent (D-glucose/L-glucose, n=11), and 0.8+/-0.1 and 0.6+/-0.1 per cent (3-O-methyl-D-glucose/L-glucose, n=6). The difference between the latter TF lost its significance after cytochalasin B (0.1-0.2 mmol/l) had been added to the amniotic compartment. It is concluded that a limited diffusive pathway across the chorionic plate of the human placenta exists and that the transfer of D-glucose depends in part on facilitated diffusion.

OBJECTIVE: It is known from animal experiments that blood flow through the ductus venosus changes with fetal strain. Therefore the ratio of umbilical vein to ductus venosus flow rate in human intrauterine growth retardation and multifetal pregnancies was investigated and compared with that in control subjects.STUDY DESIGN: Blood flow rates in the umbilical vein and in the ductus venosus, as well as peak velocity. minimum velocity, mean velocity, and pulsatility index (maximum velocity envelope curve) in the ductus venosus, were measured in women with normal pregnancies (n = 55), intrauterine growth retardation (n = 20), and multifetal pregnancies (10 women with 20 fetuses) with color Doppler ultrasonography.RESULTS: Average ductus venosus blood flow rates (mean +/- SD), normalized for estimated fetal body weight, were 60 +/- 30, 69 +/- 35, and 77 +/- 28 (ml.min(-1).kg(-1)) in control subjects, intrauterine growth retardation, and multifetal pregnancies, respectively. Umbilical vein blood flow rates amounted to 140 +/- 59, 111 +/- 54, and 141 +/- 47 (ml.min(-1).kg(-1)). Both absolute flow rates increased with gestational age, whereas normalized flow rates decreased. The percentage of umbilical blood flow passing through the ductus venosus in the control group was 43% + 9%. It was significantly increased in both intrauterine growth retardation (62% +/- 8%) and in multifetal pregnancies (55% +/- 12%). Peak velocity, minimum velocity, mean velocity, and pulsatility index in the ductus venosus were not significantly different between groups.CONCLUSION: The increased ratio of ductus venosus blood flow to umbilical vein blood flow may indicate fetal strain.

It has been demonstrated with invasive techniques in fetal lambs that the ratio of ductus venosus to umbilical vein blood flow rate (DV/UV ratio) increases during hypoxemia and infusion of catecholamines. Recently it was found in human fetuses using pulsed wave Doppler ultrasound equipment that the DV/UV ratio in fetuses with intra‐uterine growth restriction was significantly increased. The aim of the present study was to show in fetal lambs whether routine Doppler ultrasound devices were capable of determining the DV/UV ratio with sufficient reliability.

The villous trophoblast renews itself by fusion of individual stem cells (cytotrophoblasts, CT) with a functional syncytium (syncytiotrophoblast, ST). The literature indicates that fusion occurs with limited activation (proteolytic cleavage) of caspase-8 in CT and is inhibited either by blocking caspase-8 synthesis or inhibiting activation with a caspase-8-specific inhibitor, zIETD. We challenge part of this evidence: inhibition of differentiation with caspase-8 inhibitors. Br-cAMP-stimulated differentiation of isolated CT into multinucleated syncytia in culture is not blocked with three different low molecular weight inhibitors of caspase-8: broad caspase inhibitors zVAD-fmk and qVD-OPh and the caspase-8-specific inhibitor zIETD-fmk. Syncytialization was determined by desmoplakin staining of intracellular boundaries surrounding >2 nuclei and by diffusion within fused cells of long-lived cytoplasmic staining from half of original CT to the unstained half. Differentiation of isolated CT into hCGβ-secreting syncytiotrophoblast was also not blocked by the inhibitors nor was upregulation of hCGβ secretion blocked in ST-stripped and regenerated 5 day explant cultures. The ratio of CT to ST nuclei present was also not changed in explant cultures by caspase inhibitors. The effectiveness of caspase inhibitors was demonstrated by their ability to completely block TNFα-induced apoptosis. We conclude that activation of caspases in general, and caspase-8 in particular, is not required for villous CT differentiation into ST. However, another role of intact caspase-8 (proform) in CT differentiation remains possible.

Objectives: Do external Doppler indices correlated sufficiently to the peripheral resistance? Methods: The resistance of 7 fetal sheep was measured inductively and was correlated to external Doppler measurements. The correlation of different indices and methods was compared. Results: Only bloodflow velocities and the harmonic component index (HCl) yield good correlations (r greater than or equal to 7) to the peripheral resistance, PI, RI, SID-Ratio and Vpeak/Vmean showed r-values from .47 to .59. None of the Doppler parameters reached the values of indices derived from the inductive flowprobe. Conclusions: The blood flow velocities and the HCl seem to be superior to the classical indices in estimation of blood flow in the fetal aorta.

We investigated the specific uptake (reference: [H3]-L-glucose) as a measure of membrane transfer of [C14]-labeled L-ascorbic acid (AA), L-dehydroascorbic acid (DHA) and diketogulonic acid using the single injection, double tracer dilution method in the artificially perfused lobe of the near-term human placenta. The uptake of DHA (40-60%) on both the fetal and the maternal side was 3-6 times higher than the uptake of AA, whereas an uptake of diketogulonic acid was not detected. AA transport was slightly higher on the maternal side. Uptake of DHA was suppressed by phloretin and cytocholasin B, whereas AA transfer was not affected. Low sodium concentrations inhibited the uptake of DHA. D-glucose (> 20 mmol/l) inhibited the DHA uptake, and DHA inhibited D-glucose uptake but not L-alanine uptake. The Km value (self inhibition) for DHA was 6-14 mmol/l. Vitamin C enters the trophoblast predominantly as L-dehydroascorbic acid. Its transfer through the microvillous and basal membrane might use the glucose transporter, however, a specific sodium-dependent pathway is not ruled out. Our transfer data suggest an intracellular pool of vitamin C which fills up with increasing plasma DHA-concentrations.

OBJECTIVE:Do external Doppler indices correlated sufficiently to the peripheral resistance? METHODS:The resistance of 7 fetal sheep was measured inductively and was correlated to external Doppler measurements. The correlation of different indices and methods was compared. RESULTS:Only bloodflow velocities and the harmonic component index (HCI) yield good correlations (r > or = 7) to the peripheral resistance. PI, RI, S/D-Ratio and Vpeak/Vmean showed r-values from .47 to .59. None of the Doppler parameters reached the values of indices derived from the inductive flow probe. CONCLUSIONS:The blood flow velocities and the HCI seem to be superior to the classical indices in estimation of blood flow in the fetal aorta.