Drude Fugelseth

Endothelial Function and Circulating Biomarkers Are Disturbed in Women and Children After Preeclampsia

Preeclampsia is a long-term cardiovascular risk factor for the mother and possibly the offspring. Preeclampsia and cardiovascular diseases share common pathophysiological features, including endothelial dysfunction. We explored whether endothelial function, measured noninvasively, as well as circulating biomarkers reflecting lipid metabolism, angiogenesis, and inflammation, differed in paired mothers and offspring 5 to 8 years after delivery. Twenty-six mother and child pairs after pregnancies complicated by preeclampsia were compared with 17 mother and child pairs after uncomplicated pregnancies. In addition, we assessed whether concentrations of maternal circulating biomarkers at delivery predicted findings 5 to 8 years postpartum. We also included an assessment of early onset preeclampsia and specifically addressed the effects of small for gestational age. Endothelial function was significantly reduced in both mothers and children after preeclampsia when combined with a small-for-gestational-age infant compared with mothers and children after pregnancies without a small-for-gestational-age infant (mothers: P<0.001; children: P<0.05). Postpartum maternal soluble fms-like tyrosine kinase 1 (P=0.05) and high-sensitivity C-reactive protein (P=0.02) were elevated in the preeclampsia group compared with controls. High concentrations of these maternal biomarkers both at delivery and 5 to 8 years postpartum were also more frequent in preeclampsia compared with controls (P<0.05). The novelty of our study is the parallel finding of reduced endothelial function in mother and child pairs 5 to 8 years after small-for-gestational-age preeclamptic pregnancies, accompanied by increased inflammatory and antiangiogenic maternal biomarkers. This finding supports the concept of transgenerational risk of cardiovascular disease after preeclampsia.

Longitudinal strain and strain rate by tissue Doppler are more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated neonates

The function of the heart was studied in 20 asphyxiated term neonates by measuring the longitudinal peak systolic strain and peak systolic strain rate by tissue Doppler in 18 segments of the heart on days 1, 2, and 3 of life. The fractional shortening was assessed at each examination as well. Measurements were compared against measurements in 48 healthy term neonates examined by the same protocol. The function of the heart was lower in the asphyxiated neonates - peak systolic strain (mean (95% confidence interval) -19.4% (-20.4, -18.5), peak systolic strain rate -1.65 (-1.74, -1.56) per second) than in the healthy term neonates (peak systolic strain -21.7% (-22.3, -21.0), peak systolic strain rate -1.78 (-1.84, -1.74) per second; p < 0.001). Fractional shortening was similar in the asphyxiated (29.2% (26.8, 31.5)) and healthy term neonates (29.0% (27.9, 30.1); p = 0.874). The peak systolic strain differed significantly between the asphyxiated and healthy term neonates for the left basal and right basal groups of segments (p < 0.05) but not for the left apical, right apical, septum apical, or septum basal groups of segments. The peak systolic strain rate differed significantly only for the septum apical group of segments. The differences were largest on the second day of life. Measurements were similar in asphyxiated neonates with elevated and normal cardiac troponin T levels. The peak systolic strain and strain rate were in this study more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated term neonates.

Ultrasonographic study of ductus venosus in healthy neonates

AIM To assess ultrasonographically the flow pattern and the time of postnatal closure of ductus venosus related to the other fetal shunts. METHODS Fifty healthy, term neonates were studied from day 1 up to day 18 using a VingMed CFM 800A ultrasound scanner. RESULTS Ductus arteriosus was closed in 94% of the infants before day 3. Ductus venosus, however, was closed in only 12% at the same time, in 76% before day 7, and in all infants before day 18. A closed ductus venosus or ductus arteriosus did not show signs of reopening. Pulsed and colour Doppler flow could be detected across the foramen ovale in all infants during the sequential investigation. At day 1, when the pulmonary vascular resistance was still high, a reversed Doppler flow velocity signal was seen in ductus venosus in 10 infants (20%) and a bidirectional flow in ductus arteriosus in 26 (52%). Closure of the ductus venosus was not significantly correlated with closure of the ductus arteriosus nor related to sex nor weight loss. CONCLUSIONS The time of closure of the ductus venosus evaluated by ultrasonography is much later than that of the ductus arteriosus. The flow pattern in ductus venosus reflects the portocaval pressure gradient and the pressure on the right side of the heart and in the pulmonary arteries. Both the flow pattern in the ductus venosus as well as that in the ductus arteriosus may be an indication of compromised neonatal haemodynamics.

Tissue Doppler Derived Longitudinal Strain and Strain Rate During the First 3 Days of Life in Healthy Term Neonates

Tissue Doppler derived longitudinal strain and strain rate were studied in 48 healthy term neonates by measuring peak systolic strain (PSS) and peak systolic strain rate (PSSR) in 18 heart segments on day 1–3 of life. The mean PSS for each examination was −21.8% (−22.1, −21.4) [mean (95%CI)], and the mean PSSR was −1.78/s (−1.81, −1.74). Age (d), fetal shunts, and heart rate had negligible impact on measurements for any segment. The fractional shortening had negligible impact on septum and left heart segments and the pulmonary artery pressure had no impact on the right heart segments. Values varied significantly between segments and individuals, and were lower (closer to zero) in images of low quality than in images of high quality (p < 0.05). Both apical and basal segments values were lower in the septum and higher in the right ventricle than in the left ventricle (p < 0.05), except for no difference between the basal left and right segments PSSR. Apical segments values were higher than basal segments values in the right ventricle (p < 0.05) but not in the septum or the left ventricle. At present, PSS and PSSR are more feasible for quantifying differences between segment groups and patient groups than between individuals and segments within individuals.

Postnatal closure of ductus venosus in preterm infants ≤32 weeks: An ultrasonographic study

Aim: To assess ultrasonographically the flow pattern and the time of postnatal closure of ductus venosus in preterm infants ≤32 weeks. Methods: Thirty-three preterm infants ≤32 weeks were studied within the first 1 to 5 days of life and followed every second day with ultrasound until no flow was detected either through the ductus venosus or the ductus arteriosus. Results: The ductus venosus was closed in only 9% by day 3, in 40% by day 8 and 88% by day 18. All were closed by day 37. This is significantly later than in healthy term neonates. Closure of the ductus venosus was not significantly correlated with closure of ductus arteriosus. Conclusion: The ductus venosus shows a delayed closure in preterm infants, with no significant correlation to the closure of the ductus arteriosus or the condition of the infant. We speculate that immaturity of the ductus venosus and possibly increased levels of dilating prostaglandins leads to a delayed obliteration of the vessel. An open ductus venosus represents a portocaval shunt and may have metabolical and pharmacological consequences.

Superior vena cava flow: feasibility and reliability of the off-line analyses

Background Superior vena cava (SVC) flow has become a surrogate measure of systemic blood flow in neonates. Objective The aim of this study was to establish normal SVC flow values in healthy term infants the first 3 days of life and to evaluate the feasibility and reliability of the off-line analyses. Design Doppler echocardiography of SVC flow was performed in 48 healthy term infants the first 3 days of life. Off-line analyses were thereafter performed by one cardiologist to investigate the changes in SVC flow from day 1 to day 3 and to establish normal values. Intra- and inter-observer variability was analysed in a subset of 20 infants by three paediatric cardiologists. Results The authors found a decrease in mean SVC flow from 99 ml/kg/min at day 1 to 77 ml/kg/min at day 3. Reliable diameter images were obtained in 85% and velocity recordings in 81%. The mean variability of SVC flow was 17% in the intra-observer analysis and 29% in the inter-observer analysis. Conclusion The main challenge of the method is the measurement of SVC diameter. The same observer should ideally perform sequential analyses. Special caution should be taken when making clinical implications from non-optimal pictures.

Prenatal diagnosis of urinary tract anomalies The value of two ultrasound examinations

Objective. To determine when fetal urinary tract anomalies were detected by ultrasound screening during pregnancy and to discuss the possible consequences if only one early ultrasound examination is performed.

Perfluorochemical liquids modulate cell-mediated inflammatory responses

ObjectiveTo examine whether chemically different perfluorochemical liquids (PFC) (perfluorodecalin [PFD]; perflubron [PFB]) induce inflammatory responses in blood leukocytes. SettingUniversity research laboratory. DesignWhole blood from 12 healthy adults was incubated with increasing PFC concentrations and/or bacterial lipopolysaccharide. Measurements and Main Results Adhesion molecules (CD62L, CD11b), reactive oxygen species, and cytokine responses in resting and activated leukocyte subtypes were studied. Scanning and transmission electron microscopies were performed. At the highest concentrations, PFB stimulated a significant increase in resting monocytic reactive oxygen species production; all types of blood leukocytes were unresponsive to PFD. Neither PFB nor PFD changed CD62L expression; PFB increased CD11b expression in monocytes and granulocytes. PFD induced a small though significant increase in interleukin-8 secretion. When simulating a condition in which patients with severe lung disease or sepsis would be ventilated with PFC, neither PFB nor PFD plus lipopolysaccharide stimulated tumor necrosis-&agr; or interleukin-8 production above levels induced by lipopolysaccharide alone, but rather demonstrated a trend for decreased tumor necrosis factor-&agr; production. Expression of CD11b and CD62L and the production of reactive oxygen species were not changed beyond the levels induced by lipopolysaccharide alone. As a morphologic correlate to the above proinflammatory changes, surface-bound blebs and intracellular vacuoles were seen by electron microscopy. ConclusionsAt PFC concentrations comparable with those in blood during liquid ventilation, PFC liquids did not induce variables associated with inflammation. In the presence of high PFC concentrations, simulating the condition in which bronchoalveolar cells are exposed to PFC, monocytes may be induced by PFB to produce reactive oxygen species, and blood leukocytes induced by PFB to express CD11b and by PFD to secrete interleukin-8; the presence of either PFC attenuated tumor necrosis factor-&agr; production after lipopolysaccharide stimulation.

Tissue Doppler imaging in very preterm infants during the first 24???h of life: an observational study

Background Very preterm newborn infants often need cardiovascular support. More knowledge about myocardial function and factors that influence the immature myocardium may be helpful for optimising cardiovascular support in these infants. Objective Serial assessment of global myocardial function by means of colour tissue Doppler imaging (cTDI) in very and extremely preterm infants during the first 24 h of life. Study design One-centre, prospective, observational longitudinal cohort study in a third level Neonatal Intensive Care Unit. Sixty-five infants with median (range) gestational age (GA) 27 (24–31) weeks and birth weight (BW) 1049 (484–1620) g underwent echocardiographic examinations including cTDI at 5, 12 and 24 h after birth. Main outcome measures Peak systolic and peak diastolic annular velocity and peak annular displacement of the left and right ventricle. Results There was a significant reduction in systolic and diastolic velocities and displacement of both ventricles from 5 to 12 h age. From 12 to 24 h, there was a non-significant increase in myocardial velocities and displacement. At 5 h, babies with haemodynamically significant patent ductus arteriosus (PDA) had significantly higher systolic and diastolic velocities in both ventricles than those with non-significant PDA. Conclusions Myocardial tissue velocities decrease significantly from 5 to 12 h after birth in very preterm infants. Further studies are needed to confirm these results and to determine their clinical implications.

Restoration of cardiopulmonary function with 21% versus 100% oxygen after hypoxaemia in newborn pigs.

Objective: To assess the consequences of hypoxaemia and resuscitation with room air versus 100% O2 on cardiac troponin I (cTnI), cardiac output (CO), and pulmonary artery pressure (PAP) in newborn pigs. Design: Twenty anaesthetised pigs (12–36 hours; 1.7–2.7 kg) were subjected to hypoxaemia by ventilation with 8% O2. When mean arterial blood pressure fell to 15 mm Hg, or arterial base excess was ⩽ −20 mmol/l, resuscitation was performed with 21% (n  =  10) or 100% (n  =  10) O2 for 30 minutes, then ventilation with 21% O2 for 120 minutes. Blood was analysed for cTnI. Ultrasound examinations of CO and PAP (estimated from tricuspid regurgitation velocity (TR-Vmax)) were performed at baseline, during hypoxia, and at the start of and during reoxygenation. Results: cTnI increased from baseline to the end point (p<0.001), confirming a serious myocardial injury, with no differences between the 21% and 100% O2 group (p  =  0.12). TR-Vmax increased during the insult and returned towards baseline values during reoxygenation, with no differences between the groups (p  =  0.11) or between cTnI concentrations (p  =  0.31). An inverse relation was found between increasing age and TR-Vmax during hypoxaemia (p  =  0.034). CO per kg body weight increased during the early phase of hypoxaemia (p<0.001), then decreased. Changes in CO per kg were mainly due to changes in heart rate, with no differences between the groups during reoxygenation (p  =  0.298). Conclusion: Hypoxaemia affects the myocardium and PAP. During this limited period of observation, reoxygenation with 100% O2 showed no benefits compared with 21% O2 in normalising myocardial function and PAP. The important issue may be resuscitation and reoxygenation without hyperoxygenation.