Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion

Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR) but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days), rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2), apoptotic enzyme (Caspase -3 and -9) and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.     

Transrectal Doppler sonography of uterine blood flow in cows during pregnancy

Transrectal Doppler ultrasound was used for the noninvasive investigation of uterine blood flow in three cows during pregnancy. The uterine arteries ipsi and contralateral to the conceptus were scanned monthly. Blood flow was reflected by the following parameters: resistance index (RI), time-averaged maximum velocity (TAMV), diameter of the vessel (D) and the volume of blood flow (VOL). RI values were negatively correlated to all other blood flow parameters (P < 0.01). Positive correlations occurred between TAMV, D and VOL (P < 0.0001). While blood flow parameters did not differ between cows (P > 0.05), the month of gestation showed a positive effect on RI and negative effects on TAMV, D and VOL (P < 0.0001). The RI was lower and TAMV, D and VOL higher in the uterine artery ipsilateral to the conceptus (P < 0.05). RI values decreased continuously during the first 8 months of gestation and remained from then until birth at a relatively constant level. While TAMV increased especially in two-thirds of pregnancy, a relatively uniform rise of D was noticed. VOL increased exponentially with stage of gestation. The results show that transrectal Doppler sonography is a suitable, noninvasive method for the examination of uterine blood flow during pregnancy in cows. Using this technique it might be possible in the future to determine the role of uterine blood flow in cows at the risk of abortion.     

Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic

In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes in bitches with endometrial hyperplasia were lower than those of normal bitches both before and after treatment with postmating antibiotic (P = 0.04 and < 0.01, respectively). Mating-induced endometritis in bitches with endometrial hyperplasia appears to affect fertility by reducing the uterine vasodilatory response to mating and delaying clearance of uterine fluid as a result of decreased uterine contractions but the effect can be ameliorated in part by the postmating administration of antibiotic.     

The effect of semen extender,seminal plasma and raw semen on uterine and ovarian blood flow in mares

Transrectal color Doppler sonography was used to evaluate the effect of intrauterine infusion of skim milk semen extender, seminal plasma and raw semen on the endometrium and blood flow in the uterine and ovarian arteries in mares. Six Trotter mares (mean age: 12 years) were examined during estrus in three cycles. Each mare received an intrauterine infusion of 20 ml of skim milk semen extender, seminal plasma or raw semen during estrus in one of three cycles. Blood flow measurements in both uterine and ovarian arteries and the determination of intrauterine fluid via sonography were performed before each infusion and 1, 3, 6, 12, and 24 h after infusion. Forty-eight hours later, the intrauterine infusion and measurements were repeated using the same time intervals. Changes in blood flow were detected using transrectal color Doppler sonography and were evaluated using the mean time-averaged maximum velocity (TAMV) of the blood flow. Cytological and bacteriological examination of uterine swabs performed 48 h after the second infusion revealed less inflammation and bacterial growth in mares infused with skim milk semen extender than in those infused with seminal plasma or raw semen. There was an increase in intrauterine fluid as early as 1 h after infusion of any of the substances. The infusion of skim milk semen extender had no effect on uterine blood flow. Within 1 h after infusion of seminal plasma or raw semen, there was an increase in the TAMV values of both uterine arteries (P<0.05). In contrast, ovarian blood flow increased only in the artery ipsilateral to the preovulatory follicle and only after the infusion of raw semen (P<0.05). In conclusion, the changes in uterine perfusion observed after intrauterine infusion may be associated with endometrial inflammation and vasodilatory components in the seminal plasma, whereas the changes seen in ovarian blood flow are possibly attributable to the interaction between sperm and oviduct.     

Transrectal Doppler sonography of uterine blood flow during early pregnancy in mares

Transrectal color Doppler sonography was used for the noninvasive investigation of uterine blood flow in five mares. Both the left and right uterine arteries were scanned to obtain blood flow velocity waveforms during two consecutive estrous cycles and two early pregnancies in each mare. Blood flow was expressed as the time-averaged maximum velocity (TAMV) and the resistance index (RI). In all pregnancies the embryonic vesicle could be detected for the first time on Day 11 (day of ovulation: Day 0). No differences in mean TAMV and RI values of both uterine arteries were observed in comparison to the corresponding days of the estrous cycle until Day 11 of pregnancy (P>0.05). From Day 11 onwards, mean TAMV values were higher and mean RI values lower in pregnant mares than in cyclic mares (P<0.05). During the estrous cycle TAMV and RI values did not differ between the right and left uterine arteries (P>0.05). From Days 15 to 29 of pregnancy, TAMV values were consistently higher and RI values lower in the uterine artery ipsilateral to the conceptus and they had a more distinct rise and decline, respectively, compared to the contralateral uterine artery (P<0.05). The variance component estimates for the effect of mare on TAMV and RI values during pregnancy were 60 and 53%, respectively, and for the effect of day of pregnancy, they were 29 and 34%, respectively (P<0.0001). Within mares there were no significant differences between the two pregnancies with regard to blood flow (P>0.05). The results show that uterine blood supply increases in mares during the second week of pregnancy compared to cyclic mares. Furthermore there are individual variations in blood flow between mares.     

Venous occlusion plethysmography reduces arterial diameter and flow velocity

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.     

Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics

The present study was conducted to determine the impact of suppressing trophoblast remodeling of the uterine spiral arteries by prematurely elevating estrogen levels in the first trimester of baboon pregnancy on uterine and umbilical blood flow dynamics. Uteroplacental blood flow was assessed by Doppler ultrasonography after acute administration of saline (basal state) and serotonin on days 60, 100, and 160 of gestation (term: 184 days) to baboons in which uterine spiral artery remodeling had been suppressed by the administration of estradiol on days 25-59 of gestation. Maternal blood pressure in the basal state was increased (P < 0.01), and uterine artery diastolic notching and the umbilical artery pulsatility index and systolic-to-diastolic ratio, reflecting downstream flow impedance, were increased (P < 0.01) after serotonin administration on day 160, but not earlier, in baboons treated with estradiol in early gestation. These changes in uteroplacental flow dynamics in serotonin-infused, estradiol-treated animals were accompanied by a decrease (P < 0.05) in uterine and umbilical artery volume flow and fetal bradycardia. The results of this study show that suppression of uterine artery remodeling by advancing the rise in estrogen from the second trimester to the first trimester disrupted uteroplacental blood flow dynamics and fetal homeostasis after vasochallenge late in primate pregnancy.     

Metabolic acidosis decreases fetal myocardial isovolumic velocities in a chronic sheep model of increased placental vascular resistance

We hypothesized that acute fetal metabolic acidosis decreases fetal myocardial motion in a chronic sheep model of increased placental vascular resistance (R(ua)). Eleven ewes and fetuses were instrumented at 118-122 days of gestation. After 5 days of recovery and 24 h of placental embolization to increase R(ua), longitudinal myocardial velocities of the right and left ventricles and interventricular septum (IVS) were assessed at the level of the atrioventricular valve annuli via tissue Doppler imaging (TDI). Ventricular inflow (E and A waves) and outflow velocities were obtained, and cardiac outputs were calculated. All measurements were performed at baseline and during fetal acidosis caused by epidural anesthesia-induced maternal hypotension, which decreased uterine artery volume blood flow, fetal oxygenation, arterial pH, and base excess and increased lactate. Compared with baseline, the peak isovolumic myocardial contraction and relaxation velocities of the ventricles and IVS, early relaxation velocity (E') of the ventricles, and systolic velocity of the IVS decreased during metabolic acidosis. The proportion of isovolumic contraction time of the cardiac cycle increased but the isovolumic relaxation and ejection time proportions and the TDI Tei index did not change. The E-to-E' ratio for both ventricles was higher during metabolic acidosis than at baseline. During metabolic acidosis, right and left ventricular cardiac outputs remained unchanged compared with baseline. In sheep fetuses with increased R(ua) and acute metabolic acidosis, global cardiac function was preserved. However, acute metabolic acidosis impaired myocardial contractility during the isovolumic phase and relaxation during the isovolumic and early filling phases of the cardiac cycle.     

Effect of cardiac pacing on forearm vascular responses and nitric oxide function

We examined the hypothesis that changes in heart rate at rest influence bioactivity of nitric oxide (NO) in humans by examining forearm blood flow responses during cardiac pacing in six subjects. Peak forearm and mean forearm blood flows across the cardiac cycle were continuously recorded at baseline and during pacing, with the use of high-resolution brachial artery ultrasound and Doppler flow velocity measurement. The brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA). As heart rate increased, no changes in pulse pressure and mean or peak blood flow were evident. L-NMMA had no effect on brachial artery diameter, velocity, or flows compared with saline infusion. These results contrast with our recent findings that exercise involving the lower body, associated with increases in heart rate and pulse pressure, also increased forearm blood flow, the latter response being diminished by L-NMMA. These data suggest that changes in blood pressure, rather than pulse frequency, may be the stimulus for shear stress-mediated NO release in vivo.     

Transrectal Doppler sonography for evaluation of uterine blood flow throughout pregnancy in 13 cows

Once weekly from 30 to 270 days of gestation in 13 cows, Doppler ultrasound scanning (triplex Doppler system) was done to assess blood-flow parameters of both median uterine arteries. Resistance, velocity and volume indices were measured. Resistance index values were negatively correlated to all other blood-flow parameters (P<0.05), but there were positive correlations between velocity and volume indices (P<0.05). Resistance indices were lower, and velocity and volume indices were significantly higher in the median uterine artery ipsilateral versus contralateral to the fetus. Resistance indices decreased continuously during the first 36 weeks of pregnancy. Velocity values rose three-fold, whereas the area increased 20-fold and the volume increased 17-fold by the end of gestation (P<0.05). Birth weight of calves was positively correlated with blood-flow volume (r=0.34) but negatively correlated with the resistance index (r=-0.45). There were no significant differences between male versus female calves (at any stage of gestation) in the resistance, time-average maximum velocity, and volume indices (P>0.05). In conclusion, arterial blood flow was monitored with transrectal Doppler sonography in both median uterine arteries weekly throughout pregnancy in cattle; this could be very valuable for monitoring pregnancies at high risk for abnormalities of the placenta, fetus or both, e.g. cloned calves.     

Effect of the anti-oxidant tempol on fetal growth in a mouse model of fetal growth restriction

Fetal growth restriction (FGR) greatly increases the risk of perinatal morbidity and mortality and is associated with increased uterine artery resistance and levels of oxidative stress. There are currently no available treatments for this condition. The hypothesis that the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol) would improve uterine artery function and rescue fetal growth was tested in a mouse model of FGR, using the endothelial nitric oxide synthase knockout mouse (Nos3(-/-)). Pregnant Nos3(-/-) and control C57BL/6J mice were treated with the superoxide dismutase-mimetic Tempol (1 mmol/L) or vehicle from Gestational Day 12.5 to 18.5. Tempol treatment significantly increased pup weight (P < 0.05) and crown-rump length (P < 0.01) in C57BL/6J and Nos3(-/-) mice. Uterine artery resistance was increased in Nos3(-/-) mice (P < 0.05); Tempol significantly increased end diastolic velocity in Nos3(-/-) mice (P < 0.05). Superoxide production in uterine arteries did not differ between C57BL/6J and Nos3(-/-) mice but was significantly increased in placentas from Nos3(-/-) mice (P < 0.05). This was not reduced by Tempol treatment. Placental System A activity was reduced in Nos3(-/-) mice (P < 0.01); this was not improved by treatment with Tempol. Treatment of Nos3(-/-) mice with Tempol, however, was associated with reduced vascular density in the placental bed (P < 0.05). This study demonstrated that treatment with the antioxidant Tempol is able to improve fetal growth in a mouse model of FGR. This was associated with an increase in uterine artery blood flow velocity but not an improvement in uterine artery function or placental System A activity.     

Evaluation of the cerebral hemodynamic response to rhythmic handgrip.

The response of the cerebral circulation to exercise has been studied with transcranial Doppler ultrasound (TCD) because this modality provides continuous measurements of blood velocity and is well suited for the exercise environment. The use of TCD as an index of cerebral blood flow, however, requires the assumption that the diameter of the insonated vessel is constant. Here, we examine this assumption for rhythmic handgrip using a spectral index designed to measure trends in vessel flow. Nineteen normal subjects were studied during 5 min of volitional maximum rhythmic right handgrip at 1 Hz. TCD velocities from both middle arteries (left and right), blood pressure, and end-tidal PCO(2) were recorded every 10 s. A spectral weighted sum was also calculated as a flow index (FI). Averages were computed from the last 2 min of handgrip. Relative changes in velocity, FI, and pressure were calculated. The validity of FI was tested by comparing the change in diameter derived from equations relating flow and diameter. Mean blood pressure increased 23.8 +/- 17.8% (SD), and velocity increased 13.3 +/- 9.8% (left) and 9.6 +/- 8.3% (right). Although the mean change in FI was small [2.0 +/- 18. 2% (left) and 4.7 +/- 29.7% (right)], the variation was high: some subjects showed a significant increase in FI and others a significant decrease. Diameter estimates from two equations relating flow and luminal area were not significantly different. Decreases in FI were associated with estimated diameter decreases of 10%. Our data suggest that the cerebral blood flow (CBF) response to rhythmic handgrip is heterogeneous and that middle cerebral artery flow can decrease in some subjects, in agreement with prior studies using the Kety-Schmidt technique. We speculate that the velocity increase is due to sympathetically mediated vasoconstriction rather than a ubiquitous flow increase. Our data suggest that the use of ordinary TCD velocities to interpret the CBF response during exercise may be invalid.     

Uterine blood flow in the pregnant rabbit.

Two methods are described for the measurement of uterine blood flow in the pregnant rabbit. The first involves the use of a Parks ultrasonic Doppler probe placed over the exposed uterine artery. The second method uses a drop counter system connected between the uterine and jugular veins. The Doppler flowmeter was used to measure uterine arterial blood flow in twenty rabbits on Day 28 or 29 of pregnancy. No significant difference was observed between blood flow on these 2 days and the absolute blood flow to one horn (plus or minus S. E.) was found to be 16.8 plus or minus 1.4 ml/min, equivalent to 27.1 plus or minus 1.8 ml/100 g tissue/min. Using the drop recorder technique, the flow to one uterine horn in eleven rabbits on Day 27 or 28 of pregnancy was 12.5 plus or minus 1.9 ml/min, equivalent to 23.6 plus or minus 3.2 ml/100 g tissue/min. The pressure-flow relationship in the uterine vascular bed was studied using the Doppler flowmeter and graded mechanical occlusion of the arterial supply. Within the range of pressures studied, the flow was found to be linearly related to the arterio-venous pressure difference. This suggests that the uterine vascular bed was fully dilated under the conditions of study.     

Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5^th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5^th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. ¹⁴C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.     

Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow,Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

Study Overview

The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age.

Conclusion and Significance

Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system.     

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.     

Umbilical artery flow velocity waveform analysis in normal ovine pregnancy and after carunculectomy

Twenty fetal lambs were studied in utero using continuous wave Doppler ultrasound to analyse the fetal umbilical artery flow velocity waveforms. Satisfactory waveforms were obtained. Prepregnancy surgical removal of uterine caruncles was used to produce intrauterine fetal growth retardation in 14 of these ovine pregnancies of whom 8 delivered a small for gestational age fetus. In only one fetus was the umbilical artery flow velocity waveform abnormal with a high systolic diastolic ratio. We conclude that the growth restriction occurring in the ovine fetus following a reduction of placental implantation sites is not related to a restriction in the fetoplacental circulation and this is different from the most frequently observed human fetal growth retardation.     

Relationships among Doppler-derived umbilical artery absolute velocities, cardiac function, and placental volume blood flow and resistance in fetal sheep

We hypothesized that umbilical artery (UA) absolute blood flow velocities measured by Doppler ultrasonography reflect placental volume blood flow (Q(UA)) and placental vascular resistance (R(UA)) in a late gestation fetal sheep model. In addition, we examined the relationships between umbilical artery absolute blood flow velocities and parameters of fetal cardiac function. Twenty-six sheep fetuses were instrumented at 112-132 days of gestation. After a 5-day recovery period, experiments were performed under general anesthesia in 16 normal fetuses, in 5 fetuses after maternal administration of phenylephrine, and in 5 fetuses after placental embolization. The Q(UA) and arterial blood pressures were measured using a transit-time ultrasonic flow probe and a catheter placed into the descending aorta, respectively. UA peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (TAMXV), pulsatility index (PI), mean velocity (V(mean)), fetal cardiac output, ventricular ejection forces, and the proportion of isovolumetric relaxation time (IRT%) in the cardiac cycle were measured with the use of Doppler ultrasonography. Significant positive linear correlations were found between UA EDV, TAMXV, and V(mean) versus Q(UA), whereas UA PI had a significant negative correlation with Q(UA). Significant negative correlations were shown between UA EDV, TAMXV, and V(mean) versus R(UA). A significant positive correlation was present between UA PI and R(UA). Doppler-derived UA parameters did not correlate with fetal arterial blood pressures, cardiac output, ventricular ejection forces or IRT%. In fetal sheep, Doppler-derived UA PI and absolute velocities, except PSV, are closely related to directly measured Q(UA) and R(UA), validating the use of noninvasive Doppler velocimetry in the assessment of placental circulation.     

Response of Retinal Blood Flow to Systemic Hyperoxia as Measured with Dual-Beam Bidirectional Doppler Fourier-Domain Optical Coherence Tomography

Purpose

There is a long-standing interest in the study of retinal blood flow in humans. In the recent years techniques have been established to measure retinal perfusion based on optical coherence tomography (OCT). In the present study we used a technique called dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT) to characterize the effects of 100% oxygen breathing on retinal blood flow. These data were compared to data obtained with a laser Doppler velocimeter (LDV).

Methods

10 healthy subjects were studied on 2 study days. On one study day the effect of 100% oxygen breathing on retinal blood velocities was studied using dual-beam bidirectional Doppler FD-OCT. On the second study day the effect of 100% oxygen breathing on retinal blood velocities was assessed by laser Doppler velocimetry (LDV). Retinal vessel diameters were measured on both study days using a commercially available Dynamic Vessel Analyzer. Retinal blood flow was calculated based on retinal vessel diameters and red blood cell velocity.

Results

As expected, breathing of pure oxygen induced a pronounced reduction in retinal vessel diameters, retinal blood velocities and retinal blood flow on both study days (p<0.001). Blood velocity data correlated well between the two methods applied under both baseline as well as under hyperoxic conditions (r = 0.98 and r = 0.75, respectively). Data as obtained with OCT were, however, slightly higher.

Conclusion

A good correlation was found between red blood cell velocity as measured with dual-beam bidirectional Doppler FD-OCT and red blood cell velocity assessed by the laser Doppler method. Dual-beam bidirectional Doppler FD-OCT is a promising approach for studying retinal blood velocities in vivo.     

Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography--preliminary results

AIM: The goal of this study was to evaluate selected parameters of the Doppler curve of the pericallosal artery at children with hydrocephalus. METHODS: 12 patients with hydrocephalus were divided into two groups. Group 1 comprised children needing cerebrospinal fluid drainage, and group 2 comprised children without any indication for drainage or with an already inserted well-functioning drainage system. Dilatation of the cerebral ventricles was determined by transcranial ultrasonography. Following parameters of a blood flow of the pericallosal branch of the anterior cerebral artery: peak systolic blood flow velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index (RI) were observed by transcranial Doppler ultrasonography. Parameters of The Doppler curve were measured without pressure (baseline parameters) and during compression of the anterior fontanelle (pressure provocation test). RESULTS: Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39 cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92 +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04; parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV 17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased baseline and postcompressive values of RI of pericallosal artery in infants with hydrocephalus before drainage procedure and normal values of RI at children without the need for cerebrospinal fluid drainage or with a well-functioning drainage system.