Cardiac output following fetoscopic coagulation of major placental vessels in fetal sheep.

OBJECTIVES: To measure changes in cardiac output (CO) after partial cord occlusion in fetal sheep in order to investigate pathophysiological fetal adaptation mechanisms in a simulated acute placental insufficiency model under standardized conditions, with the aim of finding relevant methods for monitoring human fetuses during stress situations. METHODS: We used minimally invasive, percutaneous endoscopic techniques to close umbilical vessels in mid-gestational fetal sheep. Placental blood flow was reduced by preferentially closing first arterial and then the concomitant venous umbilical vessels within a short time interval. The investigations were carried out on 11 pregnant ewes at a median gestational age of 86 (range, 73-95) days. Major placental arteries and veins were occluded permanently by coagulation with bipolar forceps under percutaneous fetoscopic control. The fetal CO and Doppler parameters in the ductus venosus (DV), umbilical artery (UA) and umbilical vein (UV) were measured. RESULTS: In spite of heart rate reduction, the CO was not significantly affected by vessel occlusion (mean +/- SD, 500 +/- 194 mL/min before and 457 +/- 219 mL/min after coagulation) because stroke volume slightly increased from 2.65 +/- 1.16 mL/beat to 3.1 +/- 1.5 mL/beat. The right to left CO ratio remained at 1.4. The UV flow/combined CO ratio decreased from 34 +/- 14% to 25 +/- 10% after vessel coagulation. The pulsatility index in the DV increased from 0.4 +/- 0.1 to 0.7 +/- 0.4. The DV blood flow volume remained relatively constant after the intervention. The DV shunting rate, given as DV/UV flow ratio, increased significantly from 30.8 +/- 4.7% to 59.3 +/- 25.0%. CONCLUSIONS: The nearly simultaneous closure of arterial and venous umbilical vessels changed the flow pattern in the UA and significantly reduced placental blood perfusion. It did not distinctly change the blood flow volume rate through the DV, and consequently the DV shunting rate was increased. The combined CO was not significantly affected by the vascular obstruction, whereas the fraction of combined CO directed to the placenta was reduced.

Ductus venosus shunting in the fetal venous circulation: regulatory mechanisms, diagnostic methods and medical importance.

The fetal liver is located at the crossroads of the umbilical venous circulation. Anatomically, the ductus venosus (DV) and the intrahepatic branches of the portal vein are arranged in parallel. The actual DV shunting rate, i.e. the percentage of umbilical blood flow entering the DV measured by Doppler velocimetry, seems to be lower than that estimated using radioactively-labeled microspheres. In human fetuses the DV shunting rate is about 20-30%. Increases in the DV shunting rate are a general adaptational mechanism to fetal distress. Hypoxia results in a significant increase in the DV shunting rate, most probably in order to ensure an adequate supply of oxygen and glucose to vitally important organs such as the brain and heart. The mechanism of blood flow redistribution between the fetal liver and the DV is still a matter of debate. The isthmic portion of the DV contains less smooth muscle tissue than the intrahepatic branches of the portal vein, which in vitro react more forcefully in response to catecholamines than the DV. In growth-restricted human fetuses DV shunting is increased and the umbilical blood supply to the fetal liver is reduced. The long-term reduction of the hepatic blood supply may be involved in fetal growth restriction. The occlusion of the DV leads to a significant increase in cell proliferation in fetal skeletal muscle, heart, kidneys and liver, and possibly to an increase in insulin-like growth factor (IGF)-I and -II mRNA expression in the fetal liver. These findings hint at the possible role of the perfusion of the fetal liver in the control of the growth process. The quantification of DV shunting by Doppler velocimetry may improve the early recognition of fetal compromise in prenatal medicine. In this Review we summarize the published data on the anatomical structure and histology of the DV, the mechanisms of regulation of DV shunting, its role in fetal survival and growth and the possible use of the measurement of DV shunting in clinical practice.

Ductus venosus shunting in marmoset and baboon fetuses.

OBJECTIVES: The increased shunting of blood through the ductus venosus (DV) during stress situations is an important mechanism that ensures fetal survival. Although primate fetuses may serve to study the function of this important venous shunt, the rate of DV shunting has not been determined in non-human primates under normal conditions. METHODS: DV shunting was measured in 11 marmoset (eight mothers) and eight singleton baboon fetuses in mid and late gestation using Doppler ultrasound. RESULTS: DV shunting in marmosets was 39 +/- 20% (mean +/- SD) and 28 +/- 8% in baboon fetuses. Umbilical vein (UV) blood volume rate increased significantly in baboons with gestational age (GA) (UV flow volume = -111.8 + 1.6*GA; r = 0.94, P < 0.05) and slightly in marmosets (UV flow volume = -10.37 + 0.13*GA; r = 0.42, P > 0.05). Both UV diameter (r = 0.84) and the time-averaged mean UV flow velocity in baboons depended on GA (r = 0.8, P < 0.05). Distinct pulsation was found in marmoset fetuses in the UV (pulsatility index (PI) = 1.3 +/- 0.9) and the DV (PI = 1.9 +/- 1.2) with zero blood flow velocity during atrial contraction. CONCLUSIONS: A high level of pulsation is observed in the UV in marmoset fetuses. DV shunting in marmosets is higher than in baboon fetuses.

Pulmonary circulation of fetal sheep with lung hyperplasia following tracheal occlusion.

OBJECTIVES: To determine the alteration of blood flow velocity profile in the pulmonary arteries (PAs) of fetal sheep after tracheal occlusion (TO). METHODS: Doppler ultrasound investigations of the PAs, the pulmonary trunk and the ductus arteriosus were performed weekly in nine ewes (gestational age 92-98 days, term 145 days) with singleton pregnancies after TO (n = 5) and in control fetuses (n = 4). Histological examinations with morphometry of pulmonary arterial vessels and of airways were performed in both groups. RESULTS: In the control group the experiments lasted 38 +/- 6 days (mean +/- SD), and in the TO group 25 +/- 7 days. Relative lung weight was significantly higher in the TO group compared with the control group (14.5 +/- 3.4% and 4.0 +/- 0.5% of body weight). There were no significant differences in the Doppler parameters (pulsatility index, resistance index, the systolic peak, the diastolic minimum, time averaged maximum velocity) between groups. When the Doppler values of PAs in TO and control fetuses were combined, no significant differences between the left and right PA could be detected. The external diameter of peripheral PAs was significantly higher in the TO group as compared to control group (105.7 +/- 2.5 microm vs. 96.9 +/- 1.3 microm). CONCLUSIONS: We found a threefold increase of fetal lung volume after TO without significant changes of blood flow velocity profiles in the PAs of fetal sheep.

Umbilical vein blood volume flow rate and umbilical artery pulsatility as 'venous-arterial index' in the prediction of neonatal compromise.

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.

Liver blood perfusion as a possible instrument for fetal growth regulation.

Placental and fetal liver blood perfusions are reduced in intrauterine growth-restricted human fetuses. We hypothesized that changes in fetal liver blood supply can alter fetal growth. In nine ewes with twin pregnancies at a gestational age of 119+/-2 days, a stent (4 mm) was placed into the ductus venosus of one twin (DV(stent) group). Alternatively, in 17 near term sheep with twin (n=11) or singleton (n=6) pregnancies, a DV was blocked with an embolization coil (DV(coil) group) for about one week. The cell proliferation rate (pKi-67) was determined in the liver, heart, skeletal muscle, kidneys and placenta. The dilatation or occlusion of the DV did not change placental perfusion on the first day or later after surgery. The liver blood supply was decreased in the DV(stent) group by more than half from 499+/-371 to 278+/-219 ml min(-1) (mean+/-s.d., n=4), and increased two-fold in the DV(coil) group (P< 0.05). The percentage of liver/body weight was decreased from 3.9+/-0.6 per cent in control twin to 3.0+/-0.2 per cent (n=3) in the DV(stent) group. Occlusion of the DV lead to an increase in the percentage of liver/body weight from 3.4+/-0.8 per cent to 4.3+/-0.8 per cent (n=11, P< 0.05). Reduced liver blood supply in the DV(stent) group was associated with a decrease of cell proliferation in the liver from 12.43+/-2.31 to 6.5+/-0.62 (nuclei microm(2) 10(-4), n=3, P=0.058), in heart from 1.14+/-0.03 to 0.93+/-0.02 (nuclei microm(2) 10(-4), P< 0.05), and in skeletal muscle from 0.82+/-0.05 to 0.54+/-0.01 (nuclei microm(2) 10(-4), P< 0.05). The increased liver blood perfusion following occlusion of the DV increased cell proliferation sixfold in the liver, (n=9, P< 0.005) and twofold in heart muscle, skeletal muscle and the kidneys (P< 0.05), whereas no significant difference was seen in the placenta. The expression of mRNA for IGF-I and IGF-II in the liver was increased in the DV(coil) group. In conclusion, these results suggest that liver blood perfusion can regulate fetal growth.

Obstruction of ductus venosus stimulates cell proliferation in organs of fetal sheep.

In growth restricted fetuses, hepatic blood flow is reduced. This suggests the hypothesis that liver blood flow controls fetal growth. In 11 near term sheep the ductus venosus was blocked with an embolization coil in one fetus (experimental) and left patent in the twin (control). Arterial catheters were placed in both fetuses. After termination [mean (s.d.) 5 days (2) after surgery] the fetal body and organs were weighed. The cell proliferation rate (pKi-67) was determined in tissue samples of the liver, heart, skeletal muscle, kidneys and placenta (n=6). Blood flow through the umbilical vein measured by Doppler ultrasound did not differ in control and experimental fetuses [experimental: 600 (101) ml/min; control: 626 (89) ml/min]. In experimental fetuses, blood flow through the ductus venosus was negligible (colour Doppler), and thus hepatic blood flow was increased. Absolute and relative (percentage of body weight) liver weights were increased in experimental fetuses [liver weight: 119 (34) g versus 84 (17) g; relative liver weight: 4.3 (0.8) per cent versus 3.4 (0.8) per cent;P=0.002, n=11]. The cell proliferation rate was increased significantly (twofold) in heart muscle, skeletal muscle and kidneys, and sixfold in liver. It is concluded that increases of hepatic blood flow stimulate cell proliferation in major organs of the ovine fetus.

Doppler ultrasound measurements in the central circulation of anesthetized fetal sheep during obstruction of umbilical-placental blood flow.

OBJECTIVE: To establish by Doppler ultrasound the effects of acute blockage of umbilical cord vessels on the fetal central circulation. DESIGN: Experimental study in anesthetized pregnant sheep. METHODS: In 11 anesthetized pregnant sheep (0.66 of gestation), Doppler velocity profiles and/or venous flow rates were recorded in the ductus venosus, the fetal aorta, the umbilical arteries and the umbilical vein. This involved three phases. In Phase 1, the abdominal wall was closed (n = 9); Phase 2 was during fetoscopy after laparotomy (n = 8); Phase 3 was after coagulation of one of the umbilical arteries (n = 10). As an additional intervention in six fetuses, the umbilical cord was clamped for 5-15 s while blood flow velocity changes in the ductus venosus were observed. RESULTS: There were no significant differences between Doppler recordings in Phases 1 and 2. During Phase 3, the pulsatility index of the aorta and of the coagulated umbilical artery increased significantly. The umbilical vein blood flow rate was significantly reduced from a median of 408 (range, 243-575) mL/min/kg in Phase 1 to a median of 173 (range, 107-426) mL/min/kg in Phase 3, but the blood flow rate in the ductus venosus (median, 94; range, 56-148 mL/min/kg vs. median, 92; range, 33-237 mL/min/kg) remained unchanged. The ductus venosus/umbilical vein ratio increased from a median of 0.22 (range, 0.13-0.41) to 0.56 (range, 0.17-0.97) (P < 0.05). Compression of the cord (5-15 s) immediately reduced the time averaged maximum velocity in the ductus venosus from a mean of 51 (standard deviation, 11) cm/s to 20 (standard deviation, 6) cm/s (P < 0.001) without significant changes of the velocity profile. However, the pulsatility index increased from a mean of 0.55 (standard deviation, 0.19) to 1.89 (standard deviation, 0.73) (P < 0.001). CONCLUSION: Central venous flows in anesthetized fetal sheep are unaffected by laparotomy and hysterotomy. Obliteration of one umbilical artery increases the ductus venosus/umbilical vein volume flow (mL/min/kg) ratio. Compression of the umbilical cord shifts down blood flow velocity profiles in the ductus venosus, and the pulsatility index thus increases.

Unloading of baroreceptors by carotid occlusion does not increase heart rate in fetal sheep.

UNLABELLED: 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 mmHg to 53+/-8 mmHg (mean+/-S.D.) while CSP decreased from 44+/-7 mmHg to 17+/-7 mmHg. Fetal heart rate fell during occlusion significantly from 186+/-34 bpm to 159+/-26 bpm (n=20 animals). Infusion of phenylephrine (8.5-20 microg min(-1)kg(-1)) or methoxamine (60-200 microg min(-1)kg(-1)) increased mean blood pressure from 44+/-6 to 61+/-9 mmHg, and fetal heart rate decreased from 186+/-30 to 132+/-31 bpm (n=12). BCO increased systemic arterial pressure further to 70+/-11 mmHg whereas carotid sinus pressure was reduced to 31+/-13 mmHg. 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.

Efficacy of carotid collateral perfusion in anaesthetized sheep fetuses.

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.

Bipolar coagulation with small diameter forceps in animal models for in-utero cord obliteration.

The objective of this study was to evaluate the feasibility, efficacy and safety of bipolar coagulation using endoscopic forceps of diameters of 2.7 mm and less in animal models mimicking in-utero conditions. Forceps of 2.2, 2.3, 2.5 and 2.7 mm were tested in rabbits (n = 36). Vessel pairs were dissected and coagulated in a fluid environment under endoscopic vision at 15 and 25 W. The main outcome measure was the perforation rate. In fetal lambs (n = 25), umbilical cords were coagulated under sono-endoscopic control with power settings from 10 to 35 W. Main outcome measures were the duration of coagulation, perforation rate, change in the temperature of the amniotic fluid and efficacy of vessel occlusion rate. At 20-25 W, all cords were coagulated successfully without any perforation using 2.3, 2.5 or 2.7 mm forceps. Coagulation with the 2. 2 mm forceps was associated with a high perforation rate, although the design rather than the diameter of the forceps may have influenced this outcome. Bipolar coagulation with forceps between 2. 3 and 2.7 mm and appropriate power settings achieves efficacious and safe coagulation in animal models for umbilical cord occlusion.

The effect of oxytocin, prostaglandin E2 and acetylsalicylic acid on flow distribution and on the transfer of alanine, glucose and water in isolated perfused guinea pig placentae.

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.

Contraction kinetics of isolated human myometrium during menstrual cycle and pregnancy.

OBJECTIVE: To investigate the interaction between actin and myosin in the myometrium by studying the contraction kinetics of isolated samples of human myometrium. DESIGN: Experimental and observational cross-sectional study. SETTING: Eppendorf University Hospital, Hamburg. SAMPLES: Myometrium samples were taken from women in the follicular phase (n = 6) or luteal phase (n = 6) of the menstrual cycle and during pregnancy at term (n = 25). METHODS: The frequency, extent and rate of force development were determined in spontaneously active myometrial preparations. From a resting force of 2 mN, sustained tonic contractions were induced by K+-depolarisation (124 mM), or by protein kinase C activation (19 x 9 microM indolactam). The steady force was reversibly interrupted by rapid length changes (100 Hz sinus vibrations lasting 1 s, 5% of muscle length). Extent (steady plateau), as well as rate of force increase after cessation of vibrations, were derived from bi-exponential functions fitted to the time course of force recovery. RESULTS: Frequency of spontaneous contractions was higher in the follicular phase [mean (SD) 18 x 3 contractions/hour (1 x 0)] than in the luteal phase [13 x 4 contractions/hour (8 x 1)] or in pregnancy at term [8 x 8 contractions/hour (7 x 6)]. During indolactam treatment, steady force in pregnancy at term was significantly increased [8 x 8 mN (4 x 0)], compared with the follicular phase [3 x 7 mN (0 x 9)]. Force recovery was distinctly slower in pregnancy at term during indolactam treatment [time constant 99 x 2 s (57 x 9); P < 0 x 005] than during K+-depolarisation [time constant 29 x 1 s (5 x 9)], whereas in the follicular phase the rate of force recovery was faster with indolactam [16 x 8 s (7 x 1)] than with K+ depolarisation [24 x 4 s (5 x 9); P < 0 x 005]. CONCLUSIONS: The responses of human myometrium to contraction stimuli differ according to the reproductive state. Membrane depolarisation causes similar responses in all myometrial strips. In contrast, near term stimulation of protein kinase C generates a large tonic force and slow contraction kinetics, whereas early in the menstrual cycle contraction kinetics are fast.

Diffusive transfer of water and glucose across the chorionic plate of the isolated human term placenta.

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.

Doppler ultrasound evaluation of ductus venosus blood flow during acute hypoxemia in fetal lambs.

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 intrauterine 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 experiments were performed on seven near-term instrumented fetal lambs using pulsed wave Doppler ultrasound to measure flow rates (derived, in milliliters per min, from the intensity-weighted mean velocity (Vmean) and the vessel's cross-sectional area) in the ductus venosus and intra-abdominal umbilical vein. Fetal hypoxemia was induced by administering a low-oxygen gas to the ewe (5-7% oxygen, 2% carbon dioxide). Fetal arterial pO2 and heart rate decreased significantly during maternal hypoxia. The proportion of umbilical venous return passing through the ductus venous in controls was 36 +/- 5% (mean +/- SD). This increased to 53 +/- 6% (p < 0.001) because the umbilical venous blood flow fell during late hypoxemia when the heart rate had decreased by 20%. Severe hypoxemia tended to reduce the mean velocity (Vmean) and the minimum velocity (Vmin) (based on the maximum velocity envelope curve) in the ductus venosus, descending aorta and inferior vena cava. The pulsatility index of the umbilical artery significantly increased at the end of hypoxemia. We conclude that determination of the proportion of umbilical vein blood flow entering the ductus venosus by Doppler ultrasound in a clinical setting may contribute to the detection and evaluation of fetal distress.

Blood flow through the ductus venosus in singleton and multifetal pregnancies and in fetuses with intrauterine growth retardation.

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 x min(-1) x 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 x min(-1) x 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.

Engine and radiator: fetal and placental interactions for heat dissipation.

The 'engine' of fetal metabolism generates heat (3-4 W kg-1 in fetal sheep) which has to be dissipated to the maternal organism. Fetal heat may move through the amniotic/allantoic fluids to the uterine wall (conductive pathway; total conductance, 1.1 W degrees C-1 kg-1) and with the umbilical arterial blood flow (convective pathway) to the placenta. Because resistance to heat flow is larger than zero fetal temperature exceeds maternal temperature by about 0.5 degree C (0.3-1 degree C). Probably 85% of fetal heat is lost to the maternal organism through the placenta, which thus serves as the main 'radiator'. Placental heat conductivity appears to be extremely high and this may lead to impaired heat exchange (guinea-pig placenta). A computer simulation demonstrates that fetal temperature is essentially clamped to maternal temperature, and that fetal thermoregulatory efforts to gain thermal independence would be futile. Indeed, when the late gestational fetus in utero is challenged by cold stress, direct and indirect indicators of (non-shivering) thermogenesis (oxygen consumption, increase of plasma glycerol and free fatty acid levels) change only moderately. In prematurely delivered lambs, however, cold stress provokes summit metabolism and maximum heat production. Only when birth is imitated in utero (by cord clamping, external artificial lung ventilation and cooling) do thermogenic efforts approach levels typical of extra-uterine life. This suggests the presence of inhibitors of thermogenesis of placental origin, e.g. prostaglandins and adenosine. When the synthesis of prostaglandins is blocked by pretreatment with indomethacin, sheep fetuses react to intra-uterine cooling with vigorous thermogenic responses, which can be subdued by infusion of prostaglandin E2 (PGE2). Since the sheep placenta is known to produce sufficient amounts of PGE2, it seems that the placenta controls fetal thermogenic responses to some extent. This transforms the fetus into an ectothermic organism, and yet allows the newborn the full exploitation of thermoregulatory responses typical of endothermic animals.