Doppler flow velocity waveforms in the embryonic chicken heart at developmental stages corresponding to 5-8 weeks of human gestation.

OBJECTIVES: To obtain Doppler velocity waveforms from the early embryonic chicken heart by means of ultrasound biomicroscopy and to compare these waveforms at different stages of embryonic development. METHODS: We collected cardiac waveforms using high-frequency Doppler ultrasound with a 55-MHz transducer at Hamburger-Hamilton (HH) stages 18, 21 and 23, which are comparable to humans at 5 to 8 weeks of gestation. Waveforms were obtained at the inflow tract, the primitive left ventricle, the primitive right ventricle and at the outflow tract in 10 different embryos per stage. M-mode recordings were collected to study opening and closure of the cushions. By exploring the temporal relationship between the waveforms, using a secondary Doppler device, cardiac cycle events were outlined. RESULTS: Our results demonstrate that stage- and location-dependent intracardiac blood flow velocity waveforms can be obtained in the chicken embryo. The blood flow profiles assessed at the four locations in the embryonic heart demonstrated an increase in peak velocity with advancing developmental stage. In the primitive ventricle the 'passive' (P) filling peak decreased whereas the 'active' (A) filling peak increased, resulting in a decrease in P to A ratio with advancing developmental stage. M-mode recordings demonstrated that the fractional closure time of the atrioventricular cushions increased from 20% at stage HH 18 to 60% at stage HH 23. CONCLUSION: High-frequency ultrasound biomicroscopy can be used to define flow velocity waveforms in the embryonic chicken heart. This may contribute to an understanding of Doppler signals derived from valveless embryonic human hearts at 5 to 8 weeks of gestation, prior to septation.

Evaluation of volume vascularization index and flow index: a phantom study.

OBJECTIVES: Three-dimensional (3D) power Doppler ultrasonography provides indices to quantify moving blood within a volume of interest (e.g. ovary, endometrium, tumor or placenta). The purpose of this study was to determine the influence of ultrasound instrument settings on vascularization index (VI) and flow index (FI) at different flow velocities, using a specially built flow phantom with a small tube diameter. METHODS: Blood-mimicking fluid was pumped at 10-100 mL/h through a plastic tube with a diameter of 0.65 mm within a virtual spherical volume (content 137.12 cm(3)) of a Voluson 730 Expert 3D power Doppler ultrasound instrument. VI and FI were determined at different pulse repetition frequency (PRF) settings, with minimal and maximal wall motion filter (WMF) settings. The measured VI was compared with the actual VI. RESULTS: The ability to measure VI and FI at different flow velocities was highly dependent on the PRF and WMF settings. In our experimental set-up, using a PRF of 0.3 kHz, flow velocities of about 2 cm/s and higher could be registered. Measured VI was overestimated up to 44 times relative to actual VI. CONCLUSIONS: Our main finding in a laboratory set-up was a considerable overestimation of moving blood volume using 3D power Doppler ultrasound in a single small tube. The degree of overestimation depends on the spatial resolution and on the settings of the ultrasound instrument. When small vessels are involved in a clinical setting, interpretation of VI should take this overestimation of moving blood volume into account.

Blood pressure estimation in the human fetal descending aorta.

OBJECTIVES: The objectives of this study were to estimate fetal blood pressure non-invasively from two-dimensional color Doppler-derived aortic blood flow and diameter waveforms, and to compare the results with invasively derived human fetal blood pressures available from the literature. METHODS: Aortic pressures were calculated from digitally recorded color Doppler cineloops of the fetal descending aorta by applying the Womersley model in combination with the two-element Windkessel model, assuming constant pulse wave velocity during the second half of pregnancy. The results were compared with invasively derived human fetal blood pressures obtained from the literature. RESULTS: In 21 normal pregnancies the estimated mean aortic pressure regression line increased linearly from 28 mmHg at 20 weeks of gestation to 45 mmHg at 40 weeks of gestation. The pulse pressure based on the regression line increased linearly from 21 mmHg at 20 weeks of gestation to 29 mmHg at 40 weeks of gestation. The aortic compliance exhibited a log linear relationship with the gestational age and a statistically significant eightfold increase was observed between 20 and 40 weeks. The aortic downstream peripheral resistance exhibited an exponentially decaying relationship across the same gestational age range. Non-invasively derived aortic systolic and diastolic aortic pressures were comparable with previously reported invasively derived systolic and diastolic umbilical arterial pressures; however, the mean pressures differed significantly from those reported in the umbilical artery in a separate study. The aortic systolic pressures calculated in this study were significantly higher than invasively derived left ventricular systolic pressures that have been previously reported in the literature. CONCLUSIONS: This study demonstrates the feasibility of estimating arterial blood pressure in the human fetus. The method described is of potential use in assessing fetal blood pressure non-invasively, particularly for studying relative changes with time.

Wall shear stress and related hemodynamic parameters in the fetal descending aorta derived from color Doppler velocity profiles.

This paper presents a methodology for estimating the wall shear stress in the fetal descending aorta from color Doppler velocity profiles obtained during the second half of pregnancy. The Womersley model was applied to determine the wall shear stress and related hemodynamic parameters. Our analysis indicates that the aortic diameter can be modeled as a function of the gestational age in weeks as: Diameter (mm) = 0.17.ga + 0.15 (R2 = 0.64, p < 0.001). The aortic volume flow showed a log linear gestational age-related increase that fit the model: F (mL/min) = e(0.08.ga + 3.49) (R2 = 0.61, p < 0.001). The Womersley number increased linearly with gestational age from 3.3 to 6.2 (p < 0.001) and the pressure gradient decreased linearly from 2.68 to 1.16 mPa/mm (p = 0.003) during the second half of pregnancy; the mean wall shear stress for the study group was 2.2 Pa (SD = 0.59) and was independent of gestational age. This study suggests that the size of the fetal aorta adapts to flow demands and maintains constant mean wall shear stress.

Errors in predicting maximal oxygen consumption in pregnant women.

This study was designed to determine the accuracy of estimated values of maximal heart rate (HRmax) and oxygen consumption (VO2) during pregnancy. We measured HR and maximal VO2 (VO2max) at rest and during cycle (CE) and treadmill exercise (TE) tests with rapidly increasing exercise intensities during gestation and after delivery. Pregnancy was found to affect the linear relationship of HR and %VO2max so that the intercept increases with advancing gestation and the slope decreases. Estimated maximal HR (HRmax, est), 220 - age (yr) x beats/min, overestimated measured HRmax by 8% (CE) and 5% (TE). For VO2max estimated by Astrand's nomogram (VO2max, est1) and by linear extrapolation of submaximal values of HR and VO2 to HRmax, est (VO2max, est2), individual errors were large (SD 17-28%). Mean VO2max, est1 overestimated measured VO2max by 20% during CE but not during TE (-2%) and elicited the erroneous impression that VO2max decreases during CE in pregnancy. Mean VO2max, est2 values were not significantly different from measured VO2max values. This apparent accuracy resulted from two opposing errors: 1) HRmax, est overestimated HRmax, and 2) above 70% VO2max the slope of the HR-%VO2max relationship was significantly reduced. Therefore neither method to estimate VO2max can replace the measurement of VO2max.

Anaerobic threshold and respiratory compensation in pregnant women.

In an effort to explore why CO2 output (VCO2) at peak exercise is lower during pregnancy than postpartum despite little change in the peak O2 uptake (VO2), we determined the VCO2/VO2 relationship during rapidly incremental exercise and estimated the anaerobic threshold (AT) and the respiratory compensation (RC) point. We measured heart rate, VO2, VCO2, and minute ventilation (VE) at rest and during cycle exercise tests with rapidly increasing exercise intensities until maximal effort in 33 volunteers at 16-, 25-, and 35-wk gestation and postpartum. Through modification of the V-slope method, we estimated the AT and RC point for each test by nonlinear regression analysis in a three-dimensional space (defined by VE, VO2, and VCO2) for a line assumed to have two breakpoints; we found a good fit for all tests. The AT and RC points were found at exercise intensities of approximately 50 and 80% peak VO2, respectively, with no significant differences between test periods. VE was significantly higher during pregnancy than during postpartum at rest and throughout incremental exercise. A lower peak VCO2 relative to peak VO2 during pregnancy compared with postpartum was reflected by a more shallow slope of VCO2 vs. VO2 above the AT point. This suggests that during pregnancy the buffering of lactic acid is reduced.

Maximal aerobic exercise in pregnant women: heart rate, O2 consumption, CO2 production, and ventilation.

This study was to determine whether pregnancy affects maximal aerobic power. We measured heart rate, O2 uptake (VO2), CO2 production (VCO2), and ventilation at rest and during bicycle (BE) and treadmill exercise (TE) tests with rapidly increasing exercise intensities at 16, 25, and 35 wk gestation and 7 wk after delivery. Maximal heart rate was slightly lower throughout pregnancy compared with the nonpregnant state during both BE [174 +/- 2 vs. 178 +/- 2 (SE) beats/min] and TE (178 +/- 2 vs. 183 +/- 2 beats/min). Maximal VO2 was unaffected by pregnancy during BE and TE (2.20 +/- 0.08, 2.16 +/- 0.08, 2.15 +/- 0.08, and 2.19 +/- 0.08 l/min for BE and 2.45 +/- 0.08, 2.38 +/- 0.09, 2.33 +/- 0.09, and 2.39 +/- 0.08 l/min for TE at 16, 25, and 35 wk gestation and 7 wk postpartum, respectively). As a result of increased VO2 at rest, the amount of O2 available for exercise (exercise minus rest) tended to decrease with advancing gestation, reaching statistical significance only during TE at 35 wk gestation (1.99 +/- 0.08 l/min vs. 2.10 +/- 0.08 l/min postpartum). Power showed a positive linear correlation with O2 availability during BE as well as TE, and the relationship was unaffected by pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Peak ventilatory responses during cycling and swimming in pregnant and nonpregnant women.

This study was designed to determine whether pregnancy affects peak O2 uptake (VO2peak) during swimming compared with cycling. We studied 11 women at 30-34 wk gestation and 8-12 wk postpartum. We measured heart rate (HR), O2 uptake (VO2), CO2 output (VCO2), minute ventilation (VE), and lactic acid concentration. Peak HR was not significantly affected by the type of exercise or by pregnancy. VO2peak was 9% lower during swimming than during cycling but was not affected by pregnancy, with values for pregnancy cycling, pregnancy swimming, postpartum cycling, and postpartum swimming of 2.36 +/- 0.12, 2.11 +/- 0.11, 2.29 +/- 0.10, and 2.12 +/- 0.07 l/min, respectively. Peak VCO2 (VCO2peak) and peak VE were significantly lower during swimming than during cycling by 18-25%, but only VCO2peak during swimming was affected by pregnancy (-10%). Lactic acid concentrations were 12-17% lower after swimming than after cycling and 17-31% lower during pregnancy than postpartum. We conclude that perceived maximal exertion is reached at a lower percent maximal VO2 in swimming than in cycling and that the reduced energy expenditure is reflected by lower VO2peak, VCO2peak, and peak VE. Pregnancy, however, does not affect VO2peak in cycling or swimming.

Pulse pressure assessment in the human fetal descending aorta.

Pulsatile vessel diameter recordings were obtained at two different levels of the fetal descending aorta in ten third-trimester human fetuses using an echo-tracking system. A derivation of the Moens-Korteweg equation was used to estimate the pulse pressure amplitude in this vessel. The positive phase of the first derivative of the diameter curves was cross correlated to assess the propagation time of the pulse wave. It is postulated that this method minimises the measuring errors resulting from diameter pulse wave changes during propagation along the longitudinal axis of the descending aorta. It was estimated from repeated measurements that approximately 13 recordings of 5.2 s each are required to assess the mean pulse pressure amplitude for an individual fetus with an estimated random error of 10%.

Dorsal aortic flow velocity in chick embryos of stage 16 to 28.

The objective of this study was to evaluate two Doppler frequency-detection methods to measure blood flow velocity in the developing chick embryo. We compared the commonly used directional zero-crossing counter and a customized digital bidirectional spectrum analyzer. At development stages 16 up to 28 (2.5 to 6 days incubation), a reversed flow component in the dorsal aorta was demonstrated using the bidirectional spectrum analyzer. Dorsal aortic velocities obtained with the directional zero-crossing counter were significantly lower than with the bidirectional spectrum analyzer in stages 16, 20 and 28. In addition to the differences in the absolute velocity values, there was also a remarkable discrepancy in the velocity waveform shape using the two Doppler frequency processors. The calculated heart rate using the two Doppler frequency processors was identical. It is concluded that a Doppler velocity detector based on spectral analysis is superior to the hitherto used zero-crossing counter in the chick embryo. With the customized digital bidirectional spectrum analyzer, we can accurately measure the hemodynamics of the developing chick embryo.

Umbilical artery waveform analysis based on maximum, mean and mode velocity in early human pregnancy.

The objective of this study was to identify the best method for reconstructing blood-flow velocities from the early human umbilical artery to determine the physiological changes in fetal blood-flow velocity and heart rate. Pulsed Doppler recordings from the umbilical artery with a duration of approximately 7 s were made at 10-20 weeks of gestation. For reconstruction of the blood-flow velocity from the Doppler audio signal, the maximum (envelope), mean and mode frequency reconstruction methods were used. For the assessment of variability in blood-flow velocity and heart rate in the umbilical artery, the maximum velocity reconstruction method is preferred because it is relatively insensitive to noise, nonuniform insonation, and wall filter settings.

Fetal blood flow velocity waveforms in relation to changing peripheral vascular resistance.

In an acute experiment in Texel ewes, Doppler flow velocity waveforms from the fetal descending aorta were related to peripheral vascular resistance as calculated from perfusion pressure divided by electromagnetically measured volume flow in the descending aorta. Vascular resistance was increased by stepwise embolization of the peripheral circulation via repeated bolus administration of Sephadex G-25 microspheres. A rise in peripheral vascular resistance was associated with a reduction in peak and end-diastolic flow velocity and an increase in Pulsatility Index. Clinically, if similar changes are observed in growth retarded fetuses, the findings are usually interpreted to represent 'uteroplacental insufficiency'. Present data provide direct evidence that raised peripheral vascular resistance does indeed produce such waveform changes.

Blood flow measurements in the fetal descending aorta: technique and clinics.

A combination of two-dimensional and realtime pulsed-Doppler ultrasound provides a noninvasive method of measuring human fetal blood flow without side effects. By not altering the physiological conditions of the fetus, it minimizes external stimuli that might affect blood flow. However, due to the inaccessibility of the vessels under investigation, errors from the ultrasound technique arise and these are still being assessed. Studies of fetal blood flow suggest that the fetal circulation has a low peripheral resistance and that the increase in blood flow found with increasing gestational age is due predominantly to the increase in the actual dimensions of the fetal vasculature. Investigations in abnormal pregnancies, such as small-for-dates and those with cardiac arrhythmias have shown that the fetal cardiovascular system is capable of compensating efficiently to maintain normal physiological conditions, but only within the limits defined by the Frank Starling mechanism.

Placental transfer of the thromboxane synthetase inhibitor ridogrel in the late-pregnant ewe.

OBJECTIVES: To assess the occurrence of placental transfer of the thromboxane synthetase inhibitor ridogrel in the pregnant ewe and to determine its effect on prostanoid levels in the ewe and fetal lamb, on uterine contractility and on maternal and fetal hemodynamics. STUDY DESIGN: Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous infusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial samples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF1alpha, PGF2alpha, and PGE2. Maternal and fetal responses of blood flow and pressures were determined. RESULTS: Fetal ridogrel levels were 25% of maternal concentrations. Ridogrel showed rapid and marked thromboxane synthetase inhibition and augmentation of levels of prostaglandin metabolites. There was no evidence of change in amniotic pressure, uterine blood flow, maternal and fetal blood pressure and heart rate. CONCLUSION: Ridogrel is a potent thromboxane synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows similar antiplatelet activity in the ewe and the fetal lamb.

Placental transfer and maternal and fetal hemodynamic effects of ketanserin in the pregnant ewe.

OBJECTIVE: To determine placental transfer of ketanserin and to assess the effect of serotonin-2 receptor blockade by ketanserin on serotonin- and phenylephrine-induced vasoconstriction. STUDY DESIGN: Five chronically instrumented pregnant ewes at 120 days gestation were injected with 20 mg ketanserin i.v., and fetal and maternal arterial samples were obtained at predetermined intervals to assess placental transfer. Maternal and fetal responses of blood flows and pressures were determined after injected of serotonin (20 micrograms/kg) or phenylephrine (10 micrograms/kg) before and after ketanserin (0.75 mg/kg). RESULTS: In the ewe, ketanserin is transferred across the placenta and reaches measurable levels in the fetal lamb. Ketanserin blocks the maternal and fetal serotonin-induced rise in arterial pressure, but not the serotonin-induced reduction in uterine blood flow. CONCLUSION: In the pregnant ewe, the serotonin-induced rise in maternal and fetal blood pressure is effectively antagonized by ketanserin, whereas the serotonin-induced reduction in uterine blood flow is not.

Ultrasonic cervimetry to study the dilatation of the caudal cervix of the cow at parturition.

The objective of this study was to investigate the temporal changes in dilatation of the caudal cervix during induced calvings (n = 5). We used ultrasound cervimetry, allowing the continuous recording of the distance between a transmitting and receiving ultrasound crystal, which were implanted opposite to each other on the caudal rim of the cervix. We started recording between 19 and 21 h after injecting a prostaglandin analogue (PG) on day 272 of gestation. A fluid-filled catheter had been introduced transcervically between the fetal membranes and the uterine wall for measurements of intra-uterine pressure (IUP). While the characteristics of calving varied widely between the five animals, it appeared possible to divide the process of dilatation into four phases. During the latent phase, which lasted until 25-43 h after PG, no net gain in dilatation occurred. We found an acceleration phase (4.3-6.8 h), in which the dilatation rate speeds up (0.49-0.84 cm/h) in three of the cows. During the phase of maximum slope (lasting 0.5-4.8 h), we measured an even higher rate (1.47-8.48 cm/h), decreasing again during the deceleration phase (rate 0.24-2.28 cm/h) in four cows. The quality of the IUP measurements precluded us from continuously investigating the relationship between cervical dilatation and uterine contractions. However, short term simultaneous recordings revealed that the cervical opening changed momentarily in the absence of IUP during the latent phase, while during the phase of maximum slope, temporary changes of dilatation coincided with uterine contractions. We concluded that the method of ultrasound cervimetry used in this study provides a valuable way to study the process of cervical dilatation in parturient cows in vivo.

Comparison between color Doppler cineloop- and conventional spectral Doppler-derived maximum velocity and flow in the umbilical vein.

OBJECTIVE: To compare the umbilical venous flow velocity derived from color Doppler cineloop recordings with that derived from conventional spectral Doppler in normal pregnancies. METHOD: In 18 uncomplicated pregnancies between 19 and 39 weeks' gestation, color Doppler was used to find the maximum velocity in the cross-sectional vessel area of a free-floating loop of the umbilical vein. The maximum velocity was determined using the software tool HDI_Lab (Philips Medical Systems) after tracing the vessel area of interest. Conventional spectral Doppler was then used to determine the maximum velocity with the High-Q machine option. The cross-sectional area of the umbilical vein was determined using B-mode imaging and was subsequently used to determine the umbilical volume flow from both Doppler methods. Assuming a parabolic flow profile in the umbilical vein, the mean velocity is equal to half the maximum velocity. The fetal weight was estimated from fetal biometry using the four-parameter Hadlock formula. RESULTS: Maximum velocity was significantly (P = 0.003) higher with color Doppler cineloop (14.3 +/- 2.5 cm/s) compared with spectral Doppler (12.7 +/- 3.2 cm/s). Therefore, using the same cross-sectional area for both methods, the umbilical blood flow was significantly higher (P = 0.001) with color Doppler cineloop (127.9 +/- 59.0 mL/min) than it was with spectral Doppler (112.8 +/- 54.1 mL/min). The umbilical blood flow expressed as volume flow per kg fetal weight was significantly (P = 0.01) higher with color Doppler cineloop (126.0 +/- 57.0 mL/min/kg) than it was with spectral Doppler (115.0 +/- 53.0 mL/min/kg). CONCLUSIONS: Umbilical venous flow velocity derived from color Doppler cineloops is approximately 10% higher than that derived from spectral Doppler-derived velocity. The reduced angle dependence of the color Doppler cineloop technique and the large sampling area of the cross-sectional vessel should allow better determination of the correct maximum velocity in the umbilical vein.

Accuracy of sonographic estimates of fetal weight in very small infants.

OBJECTIVE: Fetal outcome is inversely related to gestational age and birth weight. Therefore, in very small fetuses, estimated weight may play an important role in clinical management. Our aim was to determine the accuracy of sonographic estimates of fetal weight in very small infants. DESIGN: Retrospective chart review. SUBJECTS: We retrospectively studied 100 consecutive infants with a birth weight of < 1000 g, at a gestational age between 24.0 and 34.0 weeks, in which biometric data < 2 weeks prior to delivery were available for analysis. METHODS: We estimated fetal weight with the use of two methods--by those of Hadlock and colleagues and Scott and colleagues--and compared the estimated values with measured birth weights. RESULTS: The infants had a mean birth weight of 742 +/- 173 (SD) g, at a gestational age of 28.1 +/- 2.0 (SD) weeks. With Hadlock's method, the mean estimated fetal weight (EFW) was 736 +/- 186 (SD) g, which was not significantly different from birth weight; the mean EFW error was 0.8 +/- 12.7 (SD) %. With Scott's method, the mean EFW was 780 +/- 185 (SD) g, which was significantly increased above birth weight; the mean EFW error was 5.7 +/- 12.5 (SD) %. The accuracy of the weight estimates was not significantly affected by the period between ultrasound examination and delivery if < 2 weeks, or by fetal growth restriction. CONCLUSION: In our population of small fetuses, Hadlock's estimates of fetal weight correlated well with measured birth weight, whereas Scott's method tended to overestimate.

The first derivative as a means of synchronizing pulsatile flow velocity and vessel diameter waveforms in the fetal descending aorta.

In order to calculate volume flow, blood flow velocity and pulsatile vessel diameter waveforms in the lower thoracic part of the descending aorta of the fetal lamb and human fetus were matched for identical cardiac cycle length by fetal ECG and the first derivative of these waveforms. Volume flow values were not essentially different using either method. There is simultaneous onset of the blood flow velocity and pulsatile vessel diameter waveforms. The first derivative can reliably replace the fetal ECG as a means of synchronizing blood flow velocity and pulsatile vessel diameter waveforms in the fetal descending aorta.