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Biomedical subjects

F van Bel

Publications and source records attributed to F van Bel.

At least 55 records · Page 3Linked to original sources

Electrical brain activity in preterm infants at risk for intracranial hemorrhage.

We studied the effect of preterm birth on electroencephalographic background activity in 20 infants < 32 weeks' gestation. Six infants developed periventricular-intraventricular hemorrhage during the study period. Four-channel 24-h cassette recordings were obtained on day 1, 3-5 and 7-9. For each of the 24-h recordings, the percentage of the time showing stage I (continuous activity), stage II (mixed activity) and stage III (discontinuous activity) epochs was calculated. In infants without periventricular-intraventricular hemorrhage, a positive linear relationship between gestational age and continuous activity and a negative linear relationship between gestational age and discontinuous activity existed in the first day recordings; in infants with periventricular-intraventricular hemorrhage, such relationships were not found. To determine if the changes in continuous and discontinuous activities during the first week of extrauterine life were different from the expected changes during a corresponding time in utero, we calculated the expected amounts of stage I and III changes for each infant. The actual changes were not significantly different from the expected values in both study groups. However, during the onset and/or extension of periventricular-intraventricular hemorrhage, depression of the electroencephalographic background activity was found.

Brain↗

Relationship between brain blood flow and carotid arterial flow in the sheep fetus.

The present study investigates whether changes in total brain blood flow can be reliably estimated by changes in carotid arterial blood flow in fetal and perinatal lambs. We therefore compared carotid arterial blood flow, measured with implanted transit-time ultrasound transducers, with brain blood flow, measured by radioactive microspheres in fetal lambs during normal oxygenation and during pulmonary ventilation with oxygen, with PO2 ranging from levels normal for the healthy fetus to levels normally seen postnatally. Cerebral perfusion pressure was modified over a wide range to alter brain blood flow: it was decreased by balloon occlusion of the brachiocephalic trunk and increased by a balloon occluder around the aortic isthmus. Carotid arterial blood flow and brain blood flow were closely related (r = 0.97, p < 0.0001). The relationship was not altered at different levels of oxygenation. However, measurements during higher cerebral perfusion pressures, obtained during aortic isthmus occlusion, had a negative influence on the agreement between carotid arterial blood flow and brain blood flow. When excluding values obtained by aortic isthmus occlusion, changes of 20% or more in brain blood flow could be predicted with carotid arterial blood flow within a confidence limit of 95%. Blood flow measurements in the carotid artery may be useful to estimate changes in brain perfusion.

Animals↗

Changes of respiratory system mechanics in ventilated lungs of preterm infants with two different schedules of surfactant treatment.

We investigated the time course of changes in the static respiratory system compliance and resistance in relationship to surfactant administration by means of single-breath and multiple-occlusion techniques. The study comprised 12 infants receiving a high-dose schedule (200 mg/kg, maximum 600 mg/kg) and 13 infants receiving a low-dose schedule (100 mg/kg, maximum 300 mg/kg) of porcine surfactant. Eight healthy preterm infants served as a comparison group. Respiratory mechanics were studied before and at 1.5, 8, and 72 h after surfactant administration. Results were related to changes in gas transfer, including an estimate of venous admixture. Static compliance improved after surfactant instillation, and changes were similar in the two treatment groups during the first eight h (0.8 In.(hour + 1) mL.kPa-1). The compliance values remained below the values of the healthy comparison group during the whole study period, but resistance remained at the same level. There was a considerable delay in changes of respiratory mechanics in relationship to the rapid fall of the venous admixture, from 27 to 19%, and the rapid increase of the transcutaneous oxygen pressure/fraction of inspired oxygen ratio from 13 to 27 kPa within the hour. There were no clues that short-term changes in compliance were masked by breathing at a higher and flatter portion of the pressure-volume curve. Both treatment schedules resulted in a similar improvement of compliance within 72 h and the two groups benefited similarly in terms of venous admixture.

Airway Resistance↗

Cerebral hemodynamics and oxygenation in preterm infants after low-vs. high-dose surfactant replacement therapy.

In thirteen preterm infants receiving surfactant (Curosurf) replacement therapy, changes in cerebral hemodynamics and oxygenation were investigated by near infrared spectroscopy. Surfactant instillation led to an instantaneous increase in cerebral blood volume (CBV) in all infants, which was primarily due to an increase in deoxygenated hemoglobin. Five infants received a low dose (100 mg/kg = 1.25 ml/kg) of surfactant and 8 a high dose (200 mg/kg = 2.50 ml/kg). A significantly larger increase in CBV was observed in the infants receiving a high dose compared to those receiving a low dose of surfactant. We conclude that cerebral perfusion is affected more after the instillation of a high dose compared to a low dose of surfactant.

Biological Products↗

Is there a relationship between indomethacin-induced reduction in neonatal cerebral blood flow velocity and prostaglandin production?

Indomethacin lowers neonatal cerebral perfusion immediately after intravenous administration. It is important to elucidate whether this reduction is mediated by inhibition of production of prostaglandins, especially prostacyclin, which plays an important role in the autoregulation of the neonatal cerebral vascular bed. We studied changes in cerebral blood flow by serial measurements of temporal mean flow velocity in the anterior cerebral artery (TMFV-ACA), relative cerebral vascular resistance (R-cer), and prostaglandins (measured as changes in thiobarbituric acid reactive substances concentration; TBARS) after a therapeutic dose of 0.1 mg/kg indomethacin administered intravenously for noninvasive closure of patent ductus arteriosus. TMFV-ACA decreased and R-cer increased immediately after the indomethacin administration with a sustained recovery to pre-indomethacin values. The TBARS concentrations, however, did not change during the study period. We conclude that the present study suggests that a therapeutic dose of 0.1 mg/kg of indomethacin has no impact on prostaglandin metabolism.

Blood Flow Velocity↗

Myocardial perfusion and performance after indomethacin administration in newborn lambs.

Indomethacin is a drug widely used to achieve pharmacologic closure of a patent ductus arteriosus in the premature infant. In several vascular beds (brain, kidney, intestine), indomethacin has been shown to cause vasoconstriction. Possible negative effects on myocardial blood flow and performance could be deleterious in premature infants with limited cardiac reserve. Before, during, and 30 and 60 min after administration of 1 mg.kg-1 of indomethacin in nine newborn lambs, we measured coronary blood flow velocity (Doppler flow probe around the left circumflex coronary artery), left ventricular (LV) pressure (by tip manometer) and volume (by conductance catheter technique), cardiac output, arterial pressure, arterial and venous saturations and calculated systemic and coronary vascular resistance, LV systolic function by the end-systolic pressure-volume relationship, and myocardial oxygen extraction. To investigate the effect of indomethacin on the flow regulation of the coronary vascular bed, we measured coronary flow and LV function under different levels of myocardial demand, achieved by stepwise occluding of the descending aorta. During indomethacin infusion, coronary and systemic vascular resistance increased significantly (by 43 and 76%, respectively), resulting in an increase in arterial pressure from 10.2 to 16.9 kPa, whereas neither coronary flow nor LV systolic function changed despite the increase in afterload. Thirty and 60 min after indomethacin, coronary and systemic vascular resistance had returned to baseline levels and LV systolic function remained unchanged. The relationship between coronary flow and cardiac demand was not different before or after indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep.

Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Carotid, not aortic, chemoreceptors mediate the fetal cardiovascular response to acute hypoxemia in lambs.

The fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, and an increase in peripheral vascular resistance. This response is mediated by the arterial chemoreceptors. To determine whether chemoreceptors in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia, we studied the response to acute hypoxemia in fetal lambs at 125 to 130 d of gestation after selective carotid (six fetuses) or aortic (five fetuses) denervation. One to 3 d after insertion of catheters, hypoxemia was induced by inflating a balloon occluder around the ewe's hypogastric artery or by giving the ewe 95% N2 and 5% O2 to breathe. The chemoreflex response was measured as decrease in heart rate per decrease in Hb O2 saturation. To validate our results, we also studied the response to chemical stimulation of the chemoreceptors by injection of sodium cyanide into the inferior vena cava. We found that carotid denervation abolished the heart rate and peripheral vascular resistance responses to hypoxemia but that aortic denervation did not. Responses after injection of sodium cyanide were similar to those seen during acute hypoxemia. We conclude that the carotid chemoreceptors, and not the aortic chemoreceptors, mediate the fetal cardiovascular response to acute hypoxemia.

Animals↗

The influence of indomethacin on the autoregulatory ability of the cerebral vascular bed in the newborn lamb.

Prevention of hyperperfusion of the brain in the perinatal period has been thought to be an important mechanism by which indomethacin reduces the risk for severe periventricular-intraventricular hemorrhage. The present study investigated whether an indomethacin-induced enhancement of the upper limit of cerebral vascular autoregulatory ability in the neonate contributed to this reduction in cerebral blood flow. In seven anesthetized newborn lambs, we measured temporal blood flow velocity (TMFV) in the carotid artery over a wide range of mean aortic blood pressures (MABP) before and 30 min after an i.v. dose of 1 mg/kg indomethacin. TMFV in the carotid artery was used as an estimate for changes in cerebral blood flow. Stepwise changes in MABP of approximately 10 mm Hg were achieved by progressive balloon occlusion of the thoracic aorta or by progressive bleeding. Multiple linear regression analysis of TMFV versus MABP, indomethacin, and the possible interactive effects confirmed that, at MABP values up to 86 mm Hg, indomethacin lowered TMFV of the carotid artery. Above 86 mm Hg, indomethacin reduced the slope of the TMFV-MABP relationship, indicating an improvement of the autoregulatory ability of the cerebral vascular bed. There was a significant interanimal variability. Thus, indomethacin may reduce the risk for PIVH by limiting cerebral blood flow, especially during increased cerebral perfusion pressures, which often occur after birth asphyxia.

Animals↗

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Biological Products↗

Changes in cerebral hemodynamics and oxygenation in the first 24 hours after birth asphyxia.

OBJECTIVE: To investigate whether or not postasphyctic cerebral hypoperfusion and decreased cerebral metabolism occur in the perinatally asphyxiated neonate, as has been reported in adults and newborn animals. METHODS: Using near-infrared spectroscopy, we monitored changes in oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), total hemoglobin (HbO2 + HbR, which represents changes in cerebral blood volume [CBV]), and cytochrome oxidase (Cytaa3, which indicates changes in oxidation level of this intracerebral mitochondrial enzyme). Thirty-one neonates (gestational age > 34 weeks), divided into three groups, were monitored between 2 and 12 hours or between 12 and 24 hours of life. Group I consisted of healthy newborns: N = 8 (2 to 12 hours) and N = 5 (12 to 24 hours). Patients in group II were moderately asphyxiated newborns but neurologically normal in the first 24 hours of life: N = 6 (2 to 12 hours) and N = 3 (12 to 24 hours). Group III consisted of severely asphyxiated newborns with an abnormal neurologic behavior within 24 hours after birth: N = 5 (2 to 12 hours) and N = 4 (12 to 24 hours). RESULTS: From 2 to 12 h, CBV levels in groups I and II were stable. In group III CBV decreased in all infants. This decrease in CBV was associated with a drop in both HbO2 and HbR. Cytaa3 was stable in groups I and II, but showed a marked decrease in two of the five infants of group III. There was a positive relationship between CBV and mean arterial blood pressure in groups II and III. Between 12 and 24 hours, all groups showed stable CBV and Cytaa3 patterns. A positive relation existed now between transcutaneous PCO2 and CBV in groups II and III. CONCLUSIONS: CBV, HbO2, HbR, and Cytaa3 decreased in the first 12 hours of life in severely asphyxiated neonates who subsequently developed neurologic abnormalities. We therefore suggest that posthypoxic-ischemic reperfusion injury of the brain during early neonatal life occurs in neonates with severe birth asphyxia.

Asphyxia Neonatorum↗

[Prevention and treatment of respiratory distress syndrome in premature infants using intratracheally administered surfactants].

OBJECTIVE: To study the effects of administration of surfactant immediately after birth (prophylactic) or after 6 hr (therapeutic) to 81 Dutch preterm infants from a multicentre trial. SETTING: University Hospital Leiden and Sint Joseph Hospital, Veldhoven. DESIGN: A randomized controlled trial with stratification for biochemical lung (im)maturity. The aims of the study were (I): to improve the TcPO2/FiO2 ratio by 40% and (2) to prevent the respiratory distress syndrome by 50% at 6 hours after birth. The secondary goal was to compare effects of prophylactic versus therapeutic use of exogenous surfactant (from 6 hours onwards) in surfactant-deficient infants. PATIENTS: The entrance criteria of the study were: (I) inborn children with a gestational age between 26 and 30 weeks, (2) elective intubation and (3) sampling of bronchotracheal or gastric aspirate. After randomization the children received surfactant within 10 minutes after birth prophylactically (n = 42) or 6 hours after birth if they needed more than 60% oxygen (13 of 39 control infants). A second dose of surfactant was given if, at 6 hours after the first dose, the FiO2 was still high (> or = 0.6). TREATMENT: We used a natural porcine surfactant preparation (Curosurf) in a dose of 200 mg/kg given through the endotracheal tube. RESULTS: The mean gestational age of the 81 infants was 28.2 weeks. The TcPO2/FiO2 ratios increased in the prophylactic group compared with the controls (38 versus 30 kPa; p < 0.05). RDS occurred less often and less severely in the prophylactic group (p < 0.05). Neonatal mortality was lower in the prophylactically treated infants (3/42) than in the control group (10/39; p < 0.05). Compared with the control infants with immature lungs, the immature prophylactically treated infants had six hours after birth higher TcPO2/FiO2 ratios (35 vs 13 kPa; p < 0.001), a 35% reduction of the incidence of RDS with a significant reduction of its severity (p < 0.05), and significantly lower mean airway pressures (0.87 versus 1.24 kPa; p < 0.005). The surfactant given 6 hours after birth to the immature controls resulted in an immediate improvement of the oxygenation. Nevertheless, these infants spent more time on the respirator and needed extra oxygen for longer periods than the immature infants prophylactically treated (p < 0.05). CONCLUSION: Surfactant, given either prophylactically or therapeutically, results in clinical improvement of children with biochemically immature lungs. A prophylactic treatment, moreover, results in reduced incidence and severity of RDS, in a significant shortening of the time spent on the respirator and in reduced need of extra oxygen compared with therapeutic treatment. We recommend to give surfactant prophylactically or at the first signs of RDS.

Gestational Age↗

The end-systolic pressure-volume relationship in young animals using the conductance technique.

Evaluation of ventricular performance by the end-systolic pressure-volume relationship (ESPVR) has been extensively performed in the adult heart using the conductance technique. We undertook this study to validate the conductance technique and to generate ESPVRs in the small heart. To validate the technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets during changes in volume and contractility. Raw conductance volumes correlated highly with cineangiographic volumes (R = 0.97), and the slope was near identity (1.11 +/- 0.04). However, 'alpha Vc-corrected' volumes correlated less well (R = 0.85), probably because of errors induced by the saline technique for alpha Vc. We evaluated the ESPVR in nine lambs by inferior vena cava (IVC) occlusion, aortic occlusion, and volume infusion at rest and during changes in contractility. Reliable and linear ESPVRs were obtained in almost all IVC and aortic occlusions but not in volume infusions. Neither slope (Ees) nor position (V14) significantly changed over time or with dobutamine, but both changed after propranolol, supporting studies showing a limited contractile reserve in the newborn. However, Ees was 25% less steep when generated by IVC occlusion as compared to aortic occlusion. We conclude that the ESPVR can be reliably generated in the small heart using the conductance technique, but that it is sensitive to the loading technique.

Age Factors↗

Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging.

Renal dysfunction has been recognized as an adverse effect of indomethacin treatment and is probably secondary to impairment of renal blood flow. We therefore evaluated renal artery blood flow velocity in 15 premature infants with a symptomatic ductus arteriosus before and during the first 12 hours after a single intravenous dose of 0.1 mg/kg of indomethacin. Renal artery blood flow velocity was measured serially by color-Doppler flow imaging and used as a qualitative measure of true renal blood flow. Indomethacin administration led to a sharp decrease in peak systolic flow velocity and temporal mean flow velocity of the renal artery. This effect was maximal at 10 minutes after indomethacin dosing; the flow velocities showed a slow recovery, reaching baseline values again at 2 hours after indomethacin dosing. We conclude that indomethacin can affect renal blood supply in the premature infant for a period of at least 1 hour after indomethacin treatment.

Blood Flow Velocity↗

The end-systolic pressure-volume relationship in the newborn lamb: effects of loading and inotropic interventions.

Indices of global systolic performance of the newborn left ventricle exceed those of the adult, despite isolated tissue studies showing immature contractile mechanisms. To evaluate contractility in situ, we investigated the end-systolic pressure-volume relationship (ESPVR) by the conductance technique in nine newborn lambs. After percutaneous placement of catheters, we generated ESPVR by inferior vena cava occlusion, aortic occlusion, and volume infusion in two control states, during three levels of dobutamine infusion, and after propranolol. We performed linear and nonlinear regression analyses of the end-systolic points and derived the slope (Ees) and volume at 14 kPa pressure. We found that reliable ESPVR could be obtained in almost all inferior vena cava and aortic occlusions (50 of 51 in each), but in only 18 of 27 volume infusions. Overall, linear regressions adequately defined the ESPVR (75 of 102 were not statistically different than nonlinear regressions; of those different, the mean linear R2 was 0.934 +/- 0.048). By multiple regression analysis, neither Ees nor volume at 14 kPa significantly changed with dobutamine, but both changed after propranolol (23% less than control and 54% greater, respectively), supporting previous studies showing a limited contractile reserve in the newborn secondary to high resting beta-adrenergic tone. Neither Ees nor volume at 14 kPa was different between control states. However, Ees was 25% less steep when generated by inferior vena cava than by aortic occlusion. We conclude that the ESPVR can be generated reliably and reproducibly in the newborn lamb and is relatively linear and sensitive to changes in contractility, but that it is also sensitive to the technique of load intervention.

Animals↗

Acceleration of blood flow velocity in the carotid artery and myocardial contractility in the newborn lamb.

We investigated the influence of quantitative changes in myocardial contractile state, reflected by changes in the end-systolic pressure-volume relationship (its slope and volume intercept) and by changes in the slope of the relationship between change in pressure per unit time and end-diastolic volume induced by beta-adrenergic stimulation or inhibition, on the Doppler derived blood flow velocity wave form of the carotid artery, using a newborn lamb model. Acceleration time of the velocity wave form was investigated during control state I, during 4 and 8 micrograms/kg/min dobutamine infusion, during control state II, and during 0.5 mg/kg propranolol infusion, respectively. Using multiple linear regression analysis with dummy variables, confounding effects such as interanimal variability were removed. Acceleration time showed a strong relationship to both the slope and the volume intercept of the end-systolic pressure-volume relationship and to the change in pressure per unit time-end-diastolic volume relationship. The relations appeared to be independent of aortic pressure and relative resistance in the vascular bed of the carotid artery. These results indicate that acceleration of cerebral blood velocity may prove to be useful in assessing changes in myocardial contractile state of the newborn.

Animals↗

Fetal and neonatal cerebral blood velocity in the normal fetus and neonate: a longitudinal Doppler ultrasound study.

In a longitudinal Doppler ultrasound study fetal and early neonatal cerebral blood flow velocities were assessed in the middle cerebral artery in 40 uncomplicated pregnancies during the third trimester of pregnancy and in 22 neonates born from these pregnancies. Peak systolic (PSFV), temporal mean (TMFV), and end diastolic flow velocities (EDFV) were determined and pulsatility index (PI = (PSFV - EDFV)/TMFV) and Pourcelot's resistance index (RI = (PSFV - EDFV)/PSFV) calculated. PSFV, TMFV and EDFV increased during the third trimester of pregnancy and were significantly higher from 36 weeks of gestation onward as compared to values obtained at 28 weeks of gestation, suggesting an increase in actual cerebral blood flow. PI and RI of the MCA did not differ significantly during this period. Immediately after birth PSFV, TMFV and EDFV decreased significantly and remained lower during the first 5 postnatal days compared to fetal values. PI and RI of the MCA tended to decrease during the first postnatal day, but stabilized afterwards.

Adult↗