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Biomedical subjects

T Kiserud

Publications and source records attributed to T Kiserud.

At least 37 records · Page 2Linked to original sources

The ductus venosus.

Until recently, our information on the ductus venosus was based on postmortem and experimental studies. The present review relates to the modern concept of this vein predominantly founded on clinical studies. Recent publications show that the blood distribution through the ductus venosus is particularly sensitive to changes in umbilical venous pressure, blood viscosity, and an active regulation of diameter of the entire ductus venosus. The mean fraction of umbilical blood shunted through the ductus is reduced from 30% to 20% during the second half of the human pregnancy, indicating that, during this period, the fetal liver has a higher priority than the shunting through the ductus venosus, apart from the compensatory redistribution needed during extreme challenges of placental compromize and hypoxemia. Additionally, the ductus venosus acts as a transmission line to the umbilical vein for pulse waves generated in the heart. These waves, reflecting cardiac function, are substantially influenced by the local variation of impedance and compliance.

Blood Flow Velocity↗

The development of high venous velocity at the fetal umbilical ring during gestational weeks 11-19.

OBJECTIVE: To determine the occurrence of high venous velocities at the umbilical ring in the normal early second trimester, based on the assumption that a narrow umbilical ring may cause obstruction and increased venous blood velocity at the abdominal wall. DESIGN: Cross-sectional study. SETTING: Hospital antenatal clinic. POPULATION: One hundred and one low risk singleton pregnancies specifically recruited for the study. METHODS: Ultrasound was used at 11-19 weeks to determine the diameter and velocity in the umbilical vein at the fetal end of the cord and at the inlet through the abdominal wall. Outcome measures 10th, 50th and 90th centiles were estimated for the time-averaged maximum velocity in the cord and at the abdominal inlet. The increase of velocity as the blood entered the abdominal wall was calculated in percent of the velocity in the cord. RESULTS: During weeks 11-12 there was hardly any difference between blood velocity in the umbilical vein at the umbilical ring and that in the cord. From week 13 onwards it was increasingly common to find blood acceleration at the umbilical ring of 50-500%. Velocity increment >50% was found in 0/12 fetuses (0%) at 11-12 weeks, 5/20 (25%) at 13-14 weeks, and in 21/28 (75%) at 17-19 weeks. CONCLUSIONS: Blood velocity is higher in the umbilical vein at the abdominal wall than the cord, particularly after 13 weeks of gestation. If acceleration of blood velocity at the umbilical ring is a sign of a narrow inlet, it seems that a progressive tightening occurs during the second trimester.

Abdominal Muscles↗

Circulatory responses to maternal hyperoxaemia and hypoxaemia assessed non-invasively in fetal sheep at 0.3-0.5 gestation in acute experiments.

OBJECTIVES: To determine fetal haemodynamic responses to hyperoxaemia and hypoxaemia in early pregnancy. DESIGN: Repeated measurements in acute experiments. SETTING: Experimental physiology laboratory. METHODS: Non-invasive Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common carotid arteries of 12 fetal lambs (0.27-0.56 gestation) during maternal hyperoxaemia and hypoxaemia under ketamine anaesthesia. The effect of gestational age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for dependent measurements and P < or = 0.05 was considered significant. Differences between groups were considered significant if the 95% confidence interval did not include zero. RESULTS: Gestational age had a significant effect on the blood velocity in the umbilical vein and ductus venosus. There were no circulatory changes during hyperoxaemia, but a simultaneous increase of pCO2 was an important confounder. However, hypoxaemia caused significantly reduced heart rate, reduced maximum and weighted mean blood velocity, and augmented pulsation in the umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus (peak velocity during systole and minimum during diastole, and time-averaged velocity) and augmented pulsation of the flow velocity. Additionally, the pulsatility of blood flow increased in the umbilical artery and was reduced in the common carotid artery. CONCLUSIONS: Maternal hypoxaemia in early pregnancy causes similar fetal circulatory responses to those in late pregnancy: bradycardia, reduced venous flow velocities, augmented pulsatility in veins and a redistributional flow velocity pattern of the umbilical and common carotid arteries.

Animals↗

Blood flow and the degree of shunting through the ductus venosus in the human fetus.

OBJECTIVES: Our goal was to determine the degree of shunting through the ductus venosus in the human fetus and its possible association with fetal growth. STUDY DESIGN: Blood flow in the umbilical vein and the fetal ductus venosus was measured in 197 low-risk pregnancies in a cross-sectional ultrasonographic study at a gestational age of 18 to 41 weeks. The degree of shunting was compared to birth weight and ponderal index. RESULTS: The average fraction shunted through the ductus venosus was 28% to 32% at 18 to 20 weeks, decreased to 22% at 25 weeks, and reached 18% at 31 weeks (with wide ranges expressed in the 10th and 90th percentiles). Fetuses <10th percentile for birth weight had significantly more shunting (1.4%) than those >90th percentile (95% confidence interval, 0.1%-2.7%; P =.04). CONCLUSIONS: In the human fetus a higher proportion of umbilical blood is directed to the liver and less is shunted through the ductus venosus, in comparison with what has previously been shown in animal experiments.

Blood Circulation↗

A mathematical model of umbilical venous pulsation.

Pulsations in the fetal heart propagate through the precordial vein and the ductus venosus but are normally not transmitted into the umbilical vein. Pulsations in the umbilical vein do occur, however, in early pregnancy and in pathological conditions. Such transmission into the umbilical vein is poorly understood. In this paper we hypothesize that the mechanical properties and the dimensions of the vessels do influence the umbilical venous pulsations, in addition to the magnitude of the pressure and flow waves generated in the fetal atria. To support this hypothesis we established a mathematical model of the umbilical vein/ductus venosus bifurcation. The umbilical vein was modeled as a compliant reservoir and the umbilical vein pressure was assumed to be equal to the stagnation pressure at the ductus venosus inlet. We calculated the index of pulsation of the umbilical vein pressure ((max-min)/mean), the reflection and transmission factors at the ductus venosus inlet, numerically and with estimates. Typical dimensions in the physiological range for the human fetus were used, while stiffness parameters were taken from fetal sheep. We found that wave transmission and reflection in the umbilical vein ductus venosus bifurcation depend on the impedance ratio between the umbilical vein and the ductus venosus, as well as the ratio of the mean velocity and the pulse wave velocity in the ductus venosus. Accordingly, the pulsations initiated by the fetal heart are transmitted upstream and may arrive in the umbilical vein with amplitudes depending on the impedance ratio and the ratio between the mean velocity and the pulse wave velocity in the ductus venosus.

Fetus↗

Amniotic gas values and acid-base status during acute maternal hyperoxemia and hypoxemia in the early fetal sheep.

OBJECTIVE: This study was undertaken to determine amniotic fluid gas values and acid-base balance during maternal hyperoxemia and hypoxemia in early pregnancy. STUDY DESIGN: Anesthetized sheep (n = 12) in early and mid pregnancy (0.3 to 0.5 gestation) were subjected to hyperoxemia followed by hypoxemia. Amniotic fluid PO (2), pH, PCO (2), bicarbonate concentration, and base excess were monitored continuously with a multiparameter Paratrend (Diametrics Medical Inc, St Paul, Minn) sensor and compared between 0.3 and 0.5 gestation. RESULTS: During maternal normoxemia all parameters were constant. At all gestational ages maternal hyperoxemia caused no changes apart from a rapid increase in amniotic fluid PO (2) (P <.001). Maternal hypoxemia led to a reduced amniotic fluid PO (2) (P <.001), whereas the PCO (2) and the bicarbonate concentration increased (P <.001). Changes in amniotic fluid gas values and acid-base balance were more pronounced at 0.3 gestation than at 0.5 gestation. Amniotic fluid Po(2) responded earlier to maternal hyperoxemia than to hypoxemia (9. 5 vs 14.3 minutes; P <.001). During hypoxemia maternal PaCO (2) changed faster than did amniotic fluid PCO (2) (P <.001). CONCLUSIONS: Acute maternal hypoxemia during early pregnancy was quickly reflected in amniotic fluid gas values and acid-base balance, whereas hyperoxygenation induced the quickest changes in amniotic fluid PO (2). The metabolic effects of maternal hyperoxemia and hypoxemia were also more pronounced during early pregnancy than at mid pregnancy.

Amniotic Fluid↗

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep.

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial PO(2) (PaO(2)) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 microg. kg(-1). min(-1)) or the alpha(1)-adrenergic agonist phenylephrine (6.5 microg. kg(-1). min(-1)) into the umbilical vein or during hypoxemia (fetal Pa(O(2)) reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an alpha(1)-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.

Adrenergic alpha-Agonists↗

Fetal venous circulation--an update on hemodynamics.

The refinements of modern ultrasound techniques permit a renewed examination of old concepts of fetal circulation. The concept of preferential streaming of umbilical blood through the foramen ovale is verified by animal experiments, and ultrasound studies have confirmed that a similar mechanism operates in human fetuses. However, the normalized umbilical flow appears to be less in the human than in fetal sheep, and decreases with advancing gestational age (115 ml min-1 kg-1 at 20 and 64 mL min-1 kg-1 at 40 weeks). Compared to the 50% shunting of umbilical blood through the ductus venosus found in animal experiments, the degree of shunting in the human fetus under physiological conditions is considerably less, 30% at 20 weeks, which decreases to 18% at 32 weeks, suggesting a higher priority of the fetal liver than previously realized. Augmented pulsatility in the precordial veins, ductus venosus, and umbilical vein is an important clinical sign that is poorly understood. Recent fluid dynamic studies show that, apart from the pressure generated in the atria, it is the stiffness of the vessel wall, compliance, and notably, impedance which modify these waves. Particularly the substantial shift in impedance at the ductus venosus-umbilical vein junction causes wave reflection and reduced transmission of waves, the result being diminished or absent pulsation in the umbilical vein.

Animals↗

[Assessment of gestational age using ultrasound--can the method be improved?].

In Norway, ultrasound measurement of the fetal biparietal diameter is used to determine the date of confinement according to Eik-Nes & Grøttum's method. We aimed to evaluate the precision of this method. 8,029 women with singleton pregnancy and spontaneous vaginal delivery were arranged in groups according to gestational age at the time of the ultrasound examination. The precision of the biparietal diameter measurement for predicting the date of birth was determined for each group. An alternative method by Altman & Chitty was also tested on the population. Eik-Nes & Grøttum's method predicts well the date of confinement if the biparietal diameter is measured at 17-20 weeks. Measurements at an earlier stage predict the date of birth with less confidence, particularly during completed gestational weeks 13-16, when the mean error reaches four days. Altman & Chitty's chart seemed to perform more evenly for the various gestational ages, but was systematically shifted by 3-4 days when used on our population. Eik-Nes & Grøttum's chart for assessing gestational age should preferably not be used before 17 weeks of gestation. Introducing new charts based on a different population is not a good option. New charts based on a Norwegian population are needed.

Confidence Intervals↗

Hemodynamics of the ductus venosus.

Although the ductus venosus has a similar function in human as in animal pregnancies (to regulate the shunting of oxygenated blood from the umbilical vein towards the left atrium), the amount of blood shunted in the human fetus seems to be less (25-40%) than in the animal (50%). The degree of shunting depends both on the resistance of the portal vasculature in the liver as well as the resistance of the ductus venosus itself. Neural and endocrine regulation plays a role in this distribution, as do fluid mechanical forces; blood viscosity and umbilical venous pressure are powerful determinants. There is a high degree of shunting at reduced umbilical venous pressure, and by increasing hematocrit, and viscosity, the distribution shifts from the liver to the ductus venosus. Additionally, the ductus venosus acts as transmission line in the opposite direction for the atrial pressure waves. Shape, viscosity, compliance, and particularly the diameter of the inlet are suggested to influence the pulsatility of the blood velocity at the ductus venosus inlet--and determine the degree of wave transmission into the umbilical vein. Occurrence of umbilical venous pulsation, an important diagnostic sign, is also dependent upon the size and compliance of the umbilical vein.

Animals↗

Pulsations of the ductus venosus blood velocity and diameter are more pronounced at the outlet than at the inlet.

OBJECTIVE: To test the hypothesis that the pulse wave emitted from the heart into the precordial veins is altered as it travels towards the periphery. STUDY DESIGN: Ultrasound diameter measurement and Doppler recording at the inlet and outlet of the fetal ductus venosus in 20 normal pregnancies (gestational age 19-41 weeks) were used to compare velocity patterns and diameters applying paired t-test and Spearman's rank correlation. RESULTS: There was a significantly lower pulsatility of the blood velocity in the ductus venosus at the inlet compared to the outlet, and, correspondingly, there was a significantly smaller diameter pulsation at the inlet than at the outlet. CONCLUSION: Both blood velocity and diameter pulsations are smaller at the inlet than at the outlet of the ductus venosus. The tapering shape of the vessel and the diameter differences at the junction with the umbilical vein are suggested to be important factors affecting the velocity waveform.

Blood Flow Velocity↗

Successful expression of beta-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein.

In utero somatic gene therapy in the later stages of pregnancy may allow targeting of organ systems which are difficult to reach later in life and to prevent the development of tissue damage otherwise caused by the early onset of inherited diseases. We report here on the percutaneous delivery of two adenoviral vectors, containing the beta-galactosidase reporter gene and the human Factor IX gene respectively, to the fetal liver and circulation by ultrasound-guided umbilical vein puncture similar to procedures used in human pregnancy. Vector spread, as detected by PCR analysis for the beta-galactosidase encoding vector, was found in almost all fetal and neonatal organs and in the maternal liver. Expression of the beta-galactosidase transgene was detected in many fetal tissues by RT-PCR. High beta-galactosidase production was shown by immuno-histochemistry predominantly in the liver, where about 30percent of the hepatocytes stained positive, and in the adrenal cortex. Production of factor IX was determined by ELISA in the plasma of treated fetuses and newborn lambs and reached at birth up to 80percent of the normal human plasma concentration. This demonstrates a very hopeful proof of principle for the development of prenatal treatment of many genetic diseases but also requires more detailed investigations with respect to the observed systemic spread of the vector.

Adenoviridae↗

Validation of diameter measurements by ultrasound: intraobserver and interobserver variations assessed in vitro and in fetal sheep.

OBJECTIVES: Blood flow evaluation in the fetus is hampered by inaccuracy in the measurement of vessel diameter. The impact of biological variation on reproducibility studies is unknown. The present study evaluated diameter measurements carried out with modern ultrasound equipment by assessing inter- and intraobserver variations. DESIGN: Repeated measurements analyzed by a general factorial model of analysis of variance. METHODS: Three observers measured repeatedly (six or more times for each tube and session) silicone tube implants (0.6, 2.2 and 6 mm), applying ultrasound imaging in eight fetal sheep, and the same silicone tubes in vitro. Analysis of variance was carried out on 199 observations made in vitro and 537 in vivo. RESULTS: The upper 95% confidence limit for the intra- and interobserver variations was higher for measurements made in vivo than in vitro. It was highest for the largest diameter and varied between 0.10 and 0.38 mm. When the diameter was determined as an average of repeated measurements, the error was reduced: six measurements in vivo had upper 95% confidence limits for intraobserver variation of 0.04 and 0.09 mm for diameters of 0.6 and 6 mm, respectively. CONCLUSIONS: The results show that ultrasound diameter measurements have a high reproducibility even for vessels of small dimensions when repeated measurements are taken with high-frequency ultrasound under favorable conditions. The low variation described in the present investigation of silicone tubes, compared to previous studies, suggests that diameter changes of living vessels represent a separate source of measurement variation.

Animals↗

Ductus venosus blood velocity in persistent pulmonary hypertension of the newborn.

AIMS: To investigate the ductus venosus flow velocity (DVFV) in infants with persistent pulmonary hypertension of the newborn (PPHN); to evaluate the DVFV pattern as a possible diagnostic supplement in neonates with PPHN and other conditions with increased right atrial pressure. METHODS: DVFV was studied in 16 neonates with PPHN on days 1-4 of postnatal life using Doppler echocardiography. DVFV was compared with that in mechanically ventilated neonates with increased intrathoracic pressure, but without signs of PPHN (n=11); with neonates with congenital heart defects resulting in right atrial pressure (n=6); and with preterm neonates without PPHN (n=46); and healthy term neonates (n=50). RESULTS: Infants with PPHN and congenital heart defects with increased right atrial pressure were regularly associated with an increased pulsatile pattern and a reversed flow velocity in ductus venosus during atrial contraction. A few short instances of reversed velocity were also noted in normal neonates before the circulation had settled during the first day after birth. CONCLUSIONS: A reversed velocity in the ductus venosus during atrial contraction at this time signifies that central venous pressure exceeds portal pressure. This negative velocity deflection is easily recognised during Doppler examination and can be recommended for diagnosing increased right atrial pressure and PPHN.

Blood Flow Velocity↗

Mechanical properties of the fetal ductus venosus and umbilical vein.

During fetal circulatory compromise, velocity pulsations in the precordial veins increase and are commonly transmitted through the ductus venosus into the umbilical vein, indicating a serious prognosis. The nature of the pulsations and their transmission into the periphery, specifically the umbilical vein, is poorly understood. We present information on the mechanical properties of fetal veins as a basis for describing the pulse wave propagation. Five fetal sheep livers with connecting veins (gestational age 0.8-0.9) were studied in vitro. The transmural pressure, obtained with a fluid-filled catheter, was reduced stepwise from 10.3 to 0 mmHg, and the diameter determined by ultrasonography. Each data set was fitted to an exponential function to determine the stiffness parameter and the area at a standard pressure, which we proposed to be 5 mmHg for the fetal venous circulation. The stiffness parameter was 6.2+/-1.8 at the ductus venosus outlet, 3.4+/-1.3 at the ductus venosus inlet, and 4.0+/-1.0 in the umbilical vein. Correspondingly, values for compliance and pulse wave velocity for the three venous sections were established for a physiological pressure range. The estimated pulse wave velocity of 1-3m/s is comparable with values estimated for veins in adults. The mechanical properties of fetal veins are comparable with those described for veins later in life. The stiffness parameter represents the elastic properties at all pressure levels and conveniently permits inference of compliance and pulse wave velocity.

Animals↗

Blood velocity profile in the ductus venosus inlet expressed by the mean/maximum velocity ratio.

Mean blood velocity (Vmean) is needed for calculating blood flow and possibly the pressure gradient across the ductus venosus. Interference from low velocities from neighbouring vessels makes the direct Doppler measurement of Vmean unreliable. Therefore, it is suggested that Vmean can be derived more reliably from the maximum velocity (Vmax) once the velocity profile, expressed as the ratio Vmean/Vmax, is known. To determine this ratio, ultrasound was performed in 10 fetal sheep during acute experiments under general anaesthesia to ensure good recording control and optimal insonation. Based on 33 Doppler measurements at the ductus venosus inlet, the ratio Vmean/Vmax was determined to be 0.69 (SD +/- 0.07) regardless of Vmax, pulsatility index, vessel diameter, or angle of insonation. These results confirm the previous prediction based on a computational model that the velocity profile is partially blunted. The equation Vmean = 0.7Vmax is recommended for determining Vmean in the ductus venosus.

Anesthesia, General↗