Diurnal variations of short-term variation and the impact of multiple recordings on measurement accuracy.

OBJECTIVE: Short-term variation (STV) from computerized cardiotocogram heart rate analysis is a parameter that complements decision making, regarding the delivery of fetuses in several high-risk situations. Although studies on the effects of gestational age and fetal pathology are convincing, there is a lack of data exploring diurnal variation and the adequacy of a single measurement. STUDY DESIGN: In this prospective observational study, fetal STV was monitored with the AN24 fetal ECG monitor (Monica Healthcare) each hour for at least 10 h in total, beginning at different times. This resulted in data covering all 24 h of the day. Seventy fetuses, low risk with respect to conditions accessible to heart rate monitoring (median 37th week of gestation) were monitored for an average of 12 h. Results of STV per hour were categorized as 'compromised' (STV<4 ms) or 'healthy', (STV⩾4 ms) to calculate the model of predictability. RESULTS: The model proposed (STV of 'healthy' fetuses: 9.6±2.6 ms, 'compromised' fetuses 3.0±0.5 ms, prevalence 1%) leads to a positive predictive value of 39%, which increased to 68 or 80% given two or three pathological (STV<4 ms) measurements, respectively. Diurnal variation was not observed. CONCLUSIONS: Single pathological STV values should be corroborated by further measurements in a 24-h interval in otherwise low-risk fetuses before inducing delivery. This may help to avoid unnecessary early births and give the fetus valuable days for intrauterine maturity.

Treatment of growth-restricted human fetuses with amino acids and glucose supplementation through a chronic fetal intravascular perinatal port system.

OBJECTIVE: Intrauterine growth restriction (IUGR) carries an increased risk of mortality and morbidity. The accepted procedure to treat IUGR fetuses is premature delivery, which may increase neonatal mortality and morbidity and retards neonatal brain development. MATERIAL AND METHODS: We report here on intravascular supplementation with amino acids and glucose of an IUGR human fetus at 33 weeks of gestation with oligohydramnios and placental insufficiency using the port system (Norfolk Medical Products, Skokie, Ill., USA). The catheter was implanted into the umbilical vein (UV) by cordocentesis, and was then connected to a subcutaneously implanted port system. The treatment course included daily infusions of amino acid solution and 10% glucose into the UV. RESULTS: Daily intravascular fetal nutrition significantly improved both fetal condition and fetal weight gain. No complications were seen. The patient was delivered by cesarean section in the 38th week of gestation. The female newborn weighed 2,130 g and was 47 cm long. Blood sampling from the UV after delivery showed no deviations of amino acids in comparison to standardized curves. In one-year follow-up the child's development and weight gain was like that of children without IUGR in the anamnesis. CONCLUSION: This is the first report of the successful use of a subcutaneously implanted intravascular perinatal port system in IUGR human fetuses for long-term administration of nutriments into the UV of a fetus.

Prenatal diagnosis of a recombinant chromosome 7 resulting in trisomy 7q11.22 --> qter.

Prenatal diagnosis of trisomy 7 is complex due to only a few reported cases. We report here on a stillborn boy with very large duplication of 7q11.22 --> qter, encompassing almost the entire long arm of chromosome 7. Ultrasound, fetal and parental chromosome banding, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (CGH) analyses were performed. Sonographic findings included growth retardation, micrognathia, ventricular septal defect (VSD), aortic coarctation, bradyarrhythmia, pericardial effusion, bilateral hydronephrosis, infravesical obstruction, and cerebellar hypoplasia. Chromosome analysis after cordocentesis at 23 weeks of gestation revealed an abnormal male karyotype with 46 chromosomes and a derivative chromosome 7 with a very large duplication of the long arm, 46,XY,der(7)(qter --> q11.2::p22 --> qter). The mother was found to carry an apparently balanced pericentric inversion, 46,XX,inv(7)(p22q11.2). Thus, the recombinant chromosome 7 [rec(7)dup(7q)inv(7)(p22.3q11.22)mat] of the fetus must have arisen through meiotic crossing-over between the inverted chromosome and the normal chromosome 7 in the maternal germline. FISH and array CGH results confirmed the recombinant chromosome 7 in the fetus and indicated a loss of 1.9 Mb at chromosome 7pter --> p22.3 (pter to 1,948,072 bp), and a gain of 87.04 Mb at chromosome 7q11.22 --> qter (71,760,154 bp to qter). The rare syndrome of almost complete trisomy 7q may be suspected in cases of growth retardation, cerebellar hypoplasia, micrognathia, aortic coarctation and VSD and hydronephrosis. Invasive prenatal diagnosis must be offered to the parents.

Successful tracheal occlusion using ultrathin fetoscopic equipment combined with real-time three-dimensional ultrasound.

OBJECTIVE: The most common complication of intrauterine tracheal balloon occlusion is the preterm premature rupture of membranes (PPROM) which increases the rate of neonatal morbidity and mortality. Ultrathin fetoscopy may be a method of reducing the risk of PPROM. MATERIALS AND METHODS: The operation was performed at the 27th week of gestation after sedation and relaxation of a fetus with bilateral congenital diaphragmatic hernia and with the liver lifted upwards into the thorax. An ultrathin sheath with a 1.2-mm fetoscope was used under real-time 3-D ultrasound guidance. The patient delivered in the 38th week of gestation and did not display PPROM after surgery until delivery. CONCLUSION: Fetal tracheal occlusion using ultrathin fetoscopic equipment in combination with real-time 3-D ultrasound may reduce the risk of PPROM.

Phenylalanine tolerance in three phenylketonuric women pregnant with fetuses of different genetic PKU status.

Pregnancy management in phenylketonuric women includes continuous dietary control starting before conception, aiming to maintain blood phenylalanine concentrations in a desirable range, irrespective of the fetal genetic PKU status. While the maternal phenylalanine hydroxylase (PAH) genotype will influence metabolic control, an effect of the fetal genetic PKU status on maternal metabolic control during pregnancy has not been described. We monitored three pregnancies of women with classical PKU by dietary protocols of daily phenylalanine intake, phenylalanine blood concentrations, and obstetric care. Patients 1 and 2 carried a heterozygous (not PKU-affected) fetus, while patient 3 was pregnant with a PKU-affected fetus (PAH p.R408W and p.R408W). The expected increase in phenylalanine tolerance during the course of pregnancy was observed in patients 1 and 2 in whom phenylalanine intake could be steadily increased from 400 to 1700 mg/day while phenylalanine blood concentrations remained in the desired range. Gain of body weight was 13.0 and 17.7 kg, respectively. In patient 3, the phenylalanine tolerance did not rise above 600 mg/day, and phenylalanine blood concentrations were above the desired range on several occasions. Caloric intake was therefore encouraged, which led to a weight gain of 20.0 kg. The course of pregnancy was otherwise normal in all three cases, and infants with normal birth weight and head circumference were born. The different phenylalanine tolerance in pregnancies with PKU-affected and non-affected fetuses suggests that PAH genotype and metabolic situation of the fetus influence maternal metabolic control. A phenylalanine tolerance remaining low in the third trimester of pregnancy may indicate fetal PKU.

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.

[Cardiac arrhythmias in the pregnant woman and the fetus]. / Herzrhythmusstörungen bei der Schwangeren und beim Fetus.

For the acute treatment of supraventricular (SVT) and ventricular tachycardias (VT) in pregnant women, electrical cardioversion with 50-100 J is indicated in all unstable patients. In stable SVT the initial therapy includes vagal maneuvers or intravenous adenosine. For long-term therapy, beta-blocking agents with beta(1)-selectivity are first-line drugs or specific anti-arrhythmic drugs. An implantable cardioverter-defibrillator is another approach. In patients with symptomatic bradycardia, a pacemaker can be implanted using echocardiography at any stage of pregnancy. Evaluation of fetal arrhythmias in clinical practice is based on assessment of the chronological relationship between atrial and ventricular contraction (M-mode and Doppler ultrasound or magnetocardiography). Most forms of SVT can be treated with transplacental administration of anti-arrhythmic drugs. Atrioventricular (AV) block in fetuses with structural heart disease is frequently associated with hydrops fetalis and intrauterine death. Administration of corticoids and beta-mimetic drugs is used to treat antibody-mediated AV block and cardiomyopathy.

Laser coagulation of placental anastomoses with a 30 degrees fetoscope in severe mid-trimester twin-twin transfusion syndrome with anterior placenta.

OBJECTIVE: To assess outcome after fetoscopic laser coagulation (FLC) of placental vascular anastomoses with the 30 degrees fetoscope in mid-trimester severe twin-to-twin transfusion syndrome (TTTS) with completely anterior placenta compared with the regular 0 degrees fetoscope in TTTS with other placental locations. METHODS: This was a prospective study of 176 consecutive monochorionic twin pregnancies undergoing FLC for severe TTTS. Of these, 51 patients required use of the 30 degrees fetoscope (study group) and 125 placental locations permitted use of the 0 degrees fetoscope (controls). RESULTS: The two groups had very similar outcomes. The median gestational age at FLC in the study group vs. control group was 21.0 (range, 17.4-24.6) weeks vs. 20.6 (range, 15.9-24.6) weeks. Both fetuses survived in 58.8% (30/51) of study patients vs. 66.4% (83/125) of controls. At least one fetus survived in 84.3% (43/51) of study patients and 88.8% (111/125) of controls (P = 0.45). Study patients delivered at a median of 34.1 (range, 25.0-38.4) weeks and controls at 34.0 (range, 25.0-40.3) weeks' gestation. CONCLUSIONS: Use of a 30 degrees fetoscope for FLC in cases of technically challenging extensive anterior placentation is associated with an outcome that is very similar to that achieved when a 0 degrees fetoscope is used in cases of more favorable placental location.

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.

Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results.

PURPOSE: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. MATERIAL AND METHODS: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N 2 O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. RESULTS: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ( approximately 40 %) from control than in the fetal brain ( approximately 10 %). CONCLUSIONS: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow.

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.

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.