Impact of Age-Related Change in Caval Flow Ratio on Hepatic Flow Distribution in the Fontan Circulation.

BACKGROUND: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. METHODS: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. RESULTS: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. CONCLUSIONS: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.

Predicting the effectiveness of drugs used for treating cardiovascular conditions in newborn infants.

BACKGROUND: Cardiovascular support (CVS) treatment failure (TF) is associated with a poor prognosis in preterm infants. METHODS: Medical charts of infants with a birth weight <1500 g who received either dopamine (Dp) or dobutamine (Db), were reviewed. Treatment response (TR) occurred if blood pressure increased >3rd centile for gestational age or superior vena cava flow was maintained >55 ml/kg/min, with decreased lactate or less negative base excess, without additional CVS. A predictive model of Dp and Db on TR was designed and the impact of TR on survival was analyzed. RESULTS: Sixty-six infants (median gestational age 27.3 weeks, median birth weight 864 g) received Dp (n = 44) or Db (n = 22). TR occurred in 59% of the cases treated with Dp and 31% with Db, p = 0.04. Machine learning identified a model that correctly labeled Db response in 90% of the cases and Dp response in 61.4%. Sixteen infants died (9% of the TR group, 39% of the TF group; p = 0.004). Brain or gut morbidity-free survival was observed in 52% vs 30% in the TR and TF groups, respectively (p = 0.08). CONCLUSIONS: New predictive models can anticipate Db but not Dp effectiveness in preterm infants. These algorithms may help the clinicians in the decision-making process. IMPACT: Failure of cardiovascular support treatment increases the risk of mortality in very low birth weight infants. A predictive model built with machine learning techniques can help anticipate treatment response to dobutamine with high accuracy. Predictive models based on artificial intelligence may guide the clinicians in the decision-making process.

Hemodynamic Changes with Umbilical Cord Milking in Nonvigorous Newborns: A Randomized Cluster Cross-over Trial.

OBJECTIVE: To assess the hemodynamic safety and efficacy of umbilical cord milking (UCM) compared with early cord clamping (ECC) in nonvigorous newborn infants enrolled in a large multicenter randomized cluster-crossover trial. STUDY DESIGN: Two hundred twenty-seven nonvigorous term or near-term infants who were enrolled in the parent UCM vs ECC trial consented for this substudy. An echocardiogram was performed at 12 ± 6 hours of age by ultrasound technicians blinded to randomization. The primary outcome was left ventricular output (LVO). Prespecified secondary outcomes included measured superior vena cava (SVC) flow, right ventricular output (RVO), peak systolic strain, and peak systolic velocity by tissue Doppler examination of the RV lateral wall and the interventricular septum. RESULTS: Nonvigorous infants receiving UCM had increased hemodynamic echocardiographic parameters as measured by higher LVO (225 ± 64 vs 187 ± 52 mL/kg/min; P < .001), RVO (284 ± 88 vs 222 ± 96 mL/kg/min; P < .001), and SVC flow (100 ± 36 vs 86 ± 40 mL/kg/min; P < .001) compared with the ECC group. Peak systolic strain was lower (-17 ± 3 vs -22 ± 3%; P < .001), but there was no difference in peak tissue Doppler flow (0.06 m/s [IQR, 0.05-0.07 m/s] vs 0.06 m/s [IQR, 0.05-0.08 m/s]). CONCLUSIONS: UCM increased cardiac output (as measured by LVO) compared with ECC in nonvigorous newborns. Overall increases in measures of cerebral and pulmonary blood flow (as measured by SVC and RVO flow, respectively) may explain improved outcomes associated with UCM (less cardiorespiratory support at birth and fewer cases of moderate-to-severe hypoxic ischemic encephalopathy) among nonvigorous newborn infants.

A novel echocardiography method to assess upper body systemic blood flow in preterm infants and comparison with superior vena cava flow measurement.

To evaluate feasibility, reproducibility, and prognostic value of a new echocardiographic method to assess systemic arterial blood flow directed to the upper part of the body (UBAF, upper body arterial flow) alternative to superior vena cava flow (SVCF) measurement. We performed echocardiographic evaluations in 106 infants in the first 2 days of life to obtain SVCF, left ventricle output (LVO), UBAF, and standard parameters of patent ductus arteriosus (PDA) significance. UBAF was calculated by subtracting from LVO the aortic arch blood flow measured immediately distally to the origin of the left subclavian artery. Main outcome measures: UBAF and SVCF agreement was assessed by Bland-Altman analysis in terms of bias, limits of agreement and repeatability index. The Intraclass Correlation Coefficient was used to measure the strength of inter-rater agreement. The agreement between UBAF and SVCF was high. The Concordance Correlation Coefficient (CCC) was 0.7434. (CCC 0.7434, 95% C.I. [0.656, 0.8111]). There was a good absolute agreement between the two raters ICC = 0.747; p value < 0.0001; 95%CI [0.601; 0.845]. Adjusting for confounding factors (BW, GA, PDA) included in the model, there was a statistically significant relationship between UBAF and SVCF. CONCLUSION: UBAF showed a strong agreement with the SCVF with a better reproducibility. Our data support UBAF as a potentially useful marker of cerebral perfusion in the evaluation of preterm infants. WHAT IS KNOWN: • Low SVC (superior vena cava) flow in the neonatal period has been associated with periventricular haemorrhage and unfavourable long-term neurodevelopmental outcome. • Ultrasound measurement of flow in SVC shows relatively high inter-operator variability. WHAT IS NEW: • Our study highlights how much overlap there is between upper-body arterial flow (UBAF) measurement and SCV flow measurement. UBAF is easier to perform and has a strong correlation with better reproducibility. • UBAF may replace measurement of cava flow as a method for haemodynamic monitoring of unstable preterm and asphyxiated infants.

Ultrasound Imaging of the Superior Vena Cava: A State-of-the-Art Review.

Greater interest in imaging the superior vena cava (SVC) in recent years has arisen because of increased focus on disorders of the right heart; the growing use of transvenous access lines, dialysis catheters, and device leads; and the emergence of right ventricular mechanical circulatory support systems via the transcatheter approach. As a low-pressure venous conduit in the right upper mediastinum, the SVC is prone to compression by various pathologic processes, to invasion by malignancies originating in nearby structures, and to complications arising from intraluminal device leads and indwelling catheters. Computed tomography and magnetic resonance venography are the modalities of choice for structural imaging of the SVC. Ultrasound allows a reasonable, yet less detailed anatomic assessment of this venous conduit. Spectral and color Doppler imaging by ultrasound are the most valuable noninvasive tools for the interrogation of SVC blood flow, a marker of the filling pattern of the right heart. Analysis of the velocity, duration, and direction of the Doppler waveforms and their phasic response to respiration makes it possible to distinguish normal from abnormal flow patterns and offers diagnostic insights into disorders that affect right heart function. The aims of this review are to demonstrate the added value SVC imaging provides during transthoracic and transesophageal echocardiographic studies, to outline its usefulness for the detection and evaluation of structural abnormalities, and to detail the role of spectral Doppler imaging in aiding the diagnosis of various disorders that affect the right heart.

The effect of placental transfusion on hemodynamics in premature newborns: a randomized controlled trial.

Despite of growing evidence of the beneficial effects of placental transfusion techniques, there is no available sufficient data about their effects on vulnerable hemodynamics and myocardium of premature infants. The purpose of this work is to study ventricular functions and hemodynamics after applying different placental transfusion techniques, delayed cord clamping (DCC), cut cord milking (C-UCM), and intact cord milking (I-UCM). Sixty-four infants delivered whether by C-section or vaginal delivery were randomly assigned to undergo C-UCM (20-30 cm), I-UCM (3-4 strippings), and DCC (30-60 s). Functional echocardiography was done on day 1 and day 3 of life for 57 infants. Primary outcome variable was superior vena cava flow measurement in infants having placental transfusion in the first 24 h of life and between 64 and 72 h. Secondary outcomes were other echocardiographic and clinical hemodynamic parameters, and biventricular functions in those infants. Of a total 196 preterm infants ≤ 32 weeks delivered in the study period, from January 2021 to August 2021, 57 infants were eligible and survived till the second examination. They were randomly assigned to the three groups. Neonates randomly assigned to DCC had significantly higher superior vena cava flow and lower right ventricular systolic function in the first 24 h of life. This finding vanished at day 3. Neonates undergone different methods of placental transfusions had similar hemoglobin, admission temperature, and mean blood pressure in the first 24 h of life. CONCLUSION: Despite their potential benefits, placental transfusions have shown to alter the hemodynamics and adversely affect myocardial function of premature neonates. TRIAL REGISTRATION: This trial was registered in the clinical trial gov NCT04811872. WHAT IS KNOWN: • Placental transfusion techniques might have benefits regarding prematurity- related morbidities and mortality. WHAT IS NEW: • Placental transfusion might adversely affect the myocardium and alter hemodynamics in premature infants.

Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring: a prospective cohort study.

Unstable hemodynamics and prematurity are the main players in intraventricular hemorrhage (IVH) development. Our objective was to study 8 the use of superior vena cava flow (SVCF), left ventricular output (LVO), and right ventricular output (RVO), and anterior cerebral artery (ACA) Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks and birth weight ≤ 1500 g. This prospective cohort study was conducted in 55NICU of Alexandria University maternity hospital. Of 147 enrolled patients, 132 infants born ≤ 32 weeks GA and birth weight ≤ 1500 g were eligible for- the study. One hundred twenty-seven infants completed the study. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVCF, LVO, and RVO using functional echocardiography in the first 24 h after birth. Patients had another two scans on DOL3 and 7 to detect IVH development. Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with OR, 3.16; 95%CI, 1.19-8.39; P = 0.02 and OR, 1.64; 95%Cl, 1.10-2.44; P = 0.02, respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P = 0.025 and 0.023, respectively. Combined use of low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity. CONCLUSIONS: There are strong relations between both low SVCF and high ACA-RI, and IVH development in premature neonates ≤ 32 weeks and birth weight ≤ 1500 g, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVCF. Maternal anemia, patent ductus arteriosus size (mm/kg), and capillary refill time were significantly associated with high ACA-RI. These findings help in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome. TRIAL REGISTRATION: This work was registered in clinical trial.gv no NCT05050032. WHAT IS KNOWN: •Whether SVCF and RI-ACA can predict IVH in preterm neonates is still debatable. WHAT IS NEW: •Low SVC flow and high ACA-RI significantly increased risk of IVH, confirming the role of hypoperfusion-reperfusion cycle in IVH development. The most striking result that combined metrics using the cut-off value of < 41 ml/kg/min for SVCF and > 0.85 for ACA-RI "in the first day of life" can correctly reject the presence of IVH in 98% of patients "during the first week of life."

Hemodynamic parameters after Delayed Cord Clamping (DCC) in term neonates: a prospective observational study.

BACKGROUND: Delayed cord clamping (DCC) is practiced worldwide, as standard care in both term and preterm babies. Our aim was to determine the hemodynamic effects of DCC on transitional circulation. MATERIAL AND METHODS: This prospective observational study was carried out in a tertiary care hospital, at Pune, India, from May 2018 to October 2019.Term neonates born during the study period were included. The primary outcome variables of the study were right ventricular output (RVO), left ventricular output (LVO), superior vena cava (SVC) flow (ml/kg/min) and heart rate(HR) at 12 ± 6 and 48 ± 6 h of life measured by point of care functional echocardiography. Inter-observer and intra-observer variability was calculated for these parameters. RESULTS: Out of a total of 2744 deliveries during the study period, 620 babies were included. Mean gestational age of the enrolled babies was 38.96 ± 1.08 weeks and mean birth weight was 2.9 ± 0.39 kg. Mean heart rate of babies recorded at 12 ± 6 h of life was 127 beats per minute (bpm) whereas it was 128 bpm at 48 ± 6 h of life. RVO {mean (SD)} was 209.55(44.89) and 205.85(46.35) ml/kg/min, LVO {mean (SD)} was 133.68(31.15) and 134.78(29.84) ml/kg/min whereas SVC flow {mean (SD)} was 106.85(26.21) and 109.29(25.11) ml/kg/min at 12 ± 6 and 48 ± 6 h of life respectively. There was good intra-observer agreement in all the variables. SGA babies had a significantly higher heart rate at 12 ± 6 h of life as compared to AGA babies, although this difference in heart rate could not be appreciated at 48 ± 6 h of life. However SGA babies had a higher LVO, RVO and SVC flow than AGA babies at both the time points of observation. CONCLUSION: After DCC there is less fluctuation in the hemodynamic parameters (heart rate, cardiac output) at the two time points of observation.. As compared to AGA babies, SGA babies had a significantly higher baseline heart rate, LVO, RVO and SVC flow. LVO of SGA babies after delayed cord clamping is found to be significantly lower than LVO seen in other studies, favoring the cardio-stabilizing effect of DCC. BRIEF RATIONALE: This is the first study with a large sample size evaluating the hemodynamic effects of DCC in term neonates by functional echocardiography. The normative data of heart rate and cardiac output of term, stable babies with small for gestational age(SGA) as a special subgroup undergoing DCC requires further evaluation.

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study.

BACKGROUND: Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. METHODS: This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20-41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. RESULTS: SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. CONCLUSIONS: Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term.

Structural recirculation and refractory hypoxemia under femoro-jugular veno-venous extracorporeal membrane oxygenation.

The performance of each veno-venous extracorporeal membrane oxygenation (vv-ECMO) configuration is determined by the anatomic context and cannula position. A mathematical model was built considering bicaval specificities to simulate femoro-jugular configuration. The main parameters to define were cardiac output (QC ), blood flow in the superior vena cava (QSVC ), extracorporeal pump flow (QEC ), and pulmonary shunt (kS-PULM ). The obtained variables were extracorporeal flow ratio in the superior vena cava (EFRSVC  = QEC /[QEC  + QSVC ]), recirculation coefficient (R), effective extracorporeal pump flow (Qeff-EC  = [1 - R] × QEC ), Qeff-EC /QC ratio, and arterial blood oxygen saturation (SaO2 ). EFRSVC increased logarithmically when QEC increased. High QC or high QSVC /QC decreased EFRSVC (range, 68%-85% for QEC of 5 L/min). R also increased following a logarithmic shape when QEC increased. The R rise was earlier and higher for low QC and high QSVC /QC (range, 12%-49% for QEC of 5 L/min). The Qeff-EC /QC ratio (between 0 and 1) was equal to EFRSVC for moderate and high QEC . The Qeff-EC /QC ratio presented the same logarithmic profile when QEC increased, reaching a plateau (range, 0.67-0.91 for QEC /QC  = 1; range, 0.75-0.94 for QEC /QC  = 1.5). The Qeff-EC /QC ratio was linearly associated with SaO2 for a given pulmonary shunt. SaO2  < 90% was observed when the pulmonary shunt was high (Qeff-EC /QC  ≤ 0.7 with kS-PULM  = 0.7 or Qeff-EC /QC  ≤ 0.8 with kS-PULM  = 0.8). Femoro-jugular vv-ECMO generates a systematic structural recirculation that gradually increases with QEC . EFRSVC determines the Qeff-EC /QC ratio, and thereby oxygen delivery and the superior cava shunt. EFRSVC cannot exceed a limit value, explaining refractory hypoxemia in extreme situations.

An alternative explanation for the phasic variations in venous flow.

BACKGROUND: Phasic venous flow variation with respiration is surrounded by controversy and not well understood. The current concept assigns a major role to the "abdominal pump." According to this model, inspiratory increases in abdominal pressure compress the vena cava, increasing its internal venous pressure and propelling blood upstream. Some have assigned a secondary role to the "thoracic pump," with the negative intrapleural pressure aiding blood flow toward the heart. The aim of the present study was to examine the phasic changes in flow, pressure, and volume in the central veins and named tributaries. METHODS: Caliber area changes were measured using intravascular ultrasonography in 37 patients undergoing iliac vein stenting. The pressure was measured in 48 patients using transducer tip catheters with electronic zero calibration. Duplex ultrasound flow in the head and neck and truncal and limb veins during inspiration and expiration was measured in 15 normal volunteers. RESULTS: The caliber of the abdominal inferior vena cava had increased by 32% and its lateral pressure had decreased significantly during inspiration. Intravenous pressure in the central veins of the chest and right atrium was positive at 6 to 14 mm Hg. Negative pressures were rarely seen and then only transiently. The internal jugular vein displayed little phasic variation. The upper limb veins displayed weak inspiratory phasicity. Phase polarity was reversed in the lower limbs, with near flow stoppage during inspiration. CONCLUSIONS: These observations conflict with the current notions of venous flow phasicity, which are based on push-pull pressure changes in the abdominal and thoracic veins. The paradoxical inspiratory inferior vena cava caliber increase probably explains the concurrent pressure decrease. Sustained negative pressures in the thoracic central veins and right atrium did not occur. We have proposed an alternate hypothesis for venous flow phasicity based on alternate stretching and relaxation of the mobile section of the great veins with respiratory movement.

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor in the lymph node: a case report of the transformation from the epithelioid cell type to the spindle cell type.

BACKGROUND: Cytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs. CASE PRESENTATION: We have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava. CONCLUSION: We first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

Rat caval vein myocardium undergoes changes in conduction characteristics during postnatal ontogenesis.

The electrophysiological properties of the superior vena cava (SVC) myocardium, which is considered a minor source of atrial arrhythmias, were studied in this study during postnatal development. Conduction properties were investigated in spontaneously active and electrically paced SVC preparations obtained from 7-60-day-old male Wistar rats using optical mapping and microelectrode techniques. The presence of high-conductance connexin 43 (Cx43) was evaluated in SVC cross-sections using immunofluorescence. It was found that SVC myocardium is excitable, electrically coupled with the atrial tissue, and conducts excitation waves at all stages of postnatal development. However, the conduction velocity (CV) of excitation and action potential (AP) upstroke velocity in SVC were significantly lower in neonatal than in adult animals and increased with postnatal maturation. Connexins Cx43 were identified in both neonatal and adult rat SVC myocardium; however, the abundance of Cx43 was significantly less in neonates. The gap junction uncoupler octanol affected conduction more profound in the neonatal than in adult SVC. We demonstrated for the first time that the conduction characteristics of SVC myocardium change from a slow-conduction (nodal) to a high-conduction (working) phenotype during postnatal ontogenesis. An age-related CV increase may occur due to changes of AP characteristics, electrical coupling, and Cx43 presence in SVC cardiomyocyte membranes. Observed changes may contribute to the low proarrhythmicity of adult caval vein cardiac tissue, while pre- or postnatal developmental abnormalities that delay the establishment of the working conduction phenotype may facilitate SVC proarrhythmia.

Associations of measures of systemic blood flow used in a randomized trial of delayed cord clamping in preterm infants.

OBJECTIVE: To determine associations of low superior vena cava (SVC) flow (≤55 ml/kg/min) and low right ventricular output (RVO) (≤150 ml/kg/min) in preterm infants. DESIGN/METHODS: An observational study in infants <30 weeks gestation randomized to receive immediate (<10 s) or delayed cord clamping (DCC) (≥60 s). RESULTS: The study enrolled 265 infants with a mean (SD) gestation 28 (2) weeks. Eighty-six (33%) infants had low SVC flow and 81 (31%) infants had low RVO. In multivariate analysis, low SVC flow was associated with gestation; low RVO was associated with DCC, gender and 5-minute Apgar; whereas mean RVO was negatively associated with both FiO2 and mean airway pressure (MAP) at 9 h and 24 h. Low SVC flow was associated with ductus arteriosus (DA) treatment. Infants with low RVO had higher mortality on univariate analysis, but this was not significant after adjusting for gestation. CONCLUSIONS: SVC flow was associated with gestation, whilst RVO was associated with placental transfusion, gender, condition at birth, and early respiratory adaptation. Compared to infants with normal values, more infants with low SVC flow were treated for DA, but infants with low RVO had no significant difference in mortality or morbidity.

Cord milking versus immediate clamping in preterm infants: a randomised controlled trial.

OBJECTIVE: To investigate whether umbilical cord milking (UCM) at birth improves systemic blood flow and short-term outcomes, as compared with immediate cord clamping (ICC). DESIGN: Randomised clinical trial. SETTING: Single tertiary care centre. PATIENTS: Infants born to eligible women presenting in preterm labour between 24 and 31 weeks' gestation. INTERVENTIONS: UCM three times at birth or ICC. OUTCOME MEASURES: Primary outcome included systemic blood flow as represented by echo-derived superior vena cava(SVC) flow at 4-6 hours after birth. The echocardiographer and interpreter were blinded to the randomisation. Secondary outcomes included cardiac output, neonatal morbidities and mortality. Analysis was by intention to treat. RESULTS: A total of 73 infants were randomised (37 to UCM and 36 to ICC). Mean (SD) gestational age was 27 (2) weeks and mean (SD) birth weight was 1040 (283) g. Haemoglobin on admission was higher in the UCM than in the ICC group (16.1 vs 15.0 g/L), p=0.049 (mean difference 1.1, 95% CI 0.003 to 2.2). No statistically significant differences were found between groups in SVC flow at 4-6 hours (88.9±37.8 and 107.3±60.1 mL/kg/min), p=0.13 (mean difference -18.4, 95% CI -41.7 to 5.0 mL/kg/min) or at 10-12 hours of age (102.5±41.8 and 90.6±28.4 mL/kg/min), p=0.17 (mean difference 12.0, 95% CI -4.7 to 28.7 mL/kg/min), cardiac output or neonatal morbidities. CONCLUSIONS: Cord milking was not shown to improve functional cardiac outcomes, neonatal morbidity or mortality. More research is needed before routine cord milking can be recommended for very preterm infants. TRIAL REGISTRATION: NCT01487187.

Hemodynamic Effects on Systemic Blood Flow and Ductal Shunting Flow after Loading Dose of Intravenous Caffeine in Preterm Infants according to the Patency of Ductus Arteriosus.

BACKGROUND: In preterm infants, caffeine citrate is used to stimulate breathing before they are weaned from mechanical ventilation and to reduce the frequency of apnea. In recent studies, effects of caffeine on the cardiovascular system have been emphasized in preterm infants with patent ductus arteriosus (PDA). METHODS: This study aimed to assess the short-term hemodynamic effects on systemic blood flow and ductal shunting flow after loading standard doses of intravenous caffeine in preterm infants. Echocardiographic studies were performed by a single investigator, before and at 1 hour and 4 hours after an intravenous infusion of a loading dose as 20 mg/kg caffeine citrate for 30 minutes. RESULTS: In 25 preterm infants with PDA, left ventricular output decreased progressively during 4 hours after caffeine loading. Superior vena cava (SVC) flow decreased and ductal shunting flow increased at 1 hour and then recovered at 4-hour to baseline values. A diameter of PDA significantly decreased only at 4-hour after caffeine loading. There were no significant changes of these hemodynamic parameters in 29 preterm infants without PDA. CONCLUSION: In preterm infants with PDA, a standard intravenous loading dose of 20 mg/kg caffeine citrate was associated with increasing ductal shunting flow and decreasing SVC flow (as a surrogate for systemic blood flow) 1 hour after caffeine loading, however, these hemodynamic parameters recovered at 4 hours according to partial constriction of the ductus arteriosus. Close monitoring of hemodynamic changes would be needed to observe the risk for pulmonary over-circulation or systemic hypo-perfusion due to transient increasing ductal shunting flow during caffeine loading in preterm infants with PDA.

A "sweet-spot" for fluid-induced oscillations in the conditioning of stem cell-based engineered heart valve tissues.

Fluid-induced shear stresses are involved in the development of cardiovascular tissues. In a tissue engineering framework, this stimulus has also been considered as a mechanical regulator of stem cell differentiation. We recently demonstrated that the fluid-oscillating effect in combination with a physiologically-relevant shear stress magnitude contributes to the formation of stem cell-derived de novo heart valve tissues. However, the range of oscillations necessary to induce favorable gene expression and engineered tissue formation is unknown. In this study, we took a computational approach to establish a range of oscillatory shear stresses that may optimize in vitro valvular tissue growth. Taking a biomimetic approach, three physiologically-relevant flow waveforms from the human: (i) aorta, (ii) pulmonary artery and (iii) superior vena cava were utilized to simulate pulsatile flow conditions within a bioreactor that housed 3 tissue specimens. Results were compared to non-physiological pulsatile flow (NPPF) and cyclic flexure-steady flow (Flex-Flow) conditions. The oscillatory shear index (OSI) was used to quantify the fluid-induced oscillations occurring on the specimen surfaces. The range of mean OSI under the physiological conditions investigated was found to be 0.18 ≤ OSI ≤ 0.23. On the other hand, NPPF and Flex-Flow environments yielded a mean OSI of 0.37 and 0.11 respectively, which were 46% higher and 45% lower than physiological conditions. Moreover, we subsequently conducted OSI-based human bone marrow stem cell (HBMSC) culture experiments which resulted in preferential valvular gene expression and phenotype (significant upregulation of BMP, KLF2A, CD31 and α-SMA using an OSI of 0.23 in comparison to a lower OSI of 0.10 or a higher OSI of 0.38; p < .05). These findings suggest that a distinct range or a "sweet-spot" for physiological OSI exists in the mechanical conditioning of tissue engineered heart valves grown from stem cell sources. We conclude that in vitro heart valve matrix development could be further enhanced by simultaneous exposure of the engineered tissues to physiologically-relevant magnitudes of both fluid-induced oscillations and shear stresses.

Right atrial pressure and venous return during cardiopulmonary bypass.

The relevance of right atrial pressure (RAP) as the backpressure for venous return (QVR) and mean systemic filling pressure as upstream pressure is controversial during dynamic changes of circulation. To examine the immediate response of QVR (sum of caval vein flows) to changes in RAP and pump function, we used a closed-chest, central cannulation, heart bypass porcine preparation (n = 10) with venoarterial extracorporeal membrane oxygenation. Mean systemic filling pressure was determined by clamping extracorporeal membrane oxygenation tubing with open or closed arteriovenous shunt at euvolemia, volume expansion (9.75 ml/kg hydroxyethyl starch), and hypovolemia (bleeding 19.5 ml/kg after volume expansion). The responses of RAP and QVR were studied using variable pump speed at constant airway pressure (PAW) and constant pump speed at variable PAW Within each volume state, the immediate changes in QVR and RAP could be described with a single linear regression, regardless of whether RAP was altered by pump speed or PAW (r2 = 0.586-0.984). RAP was inversely proportional to pump speed from zero to maximum flow (r2 = 0.859-0.999). Changing PAW caused immediate, transient, directionally opposite changes in RAP and QVR (RAP: P ≤ 0.002 and QVR: P ≤ 0.001), where the initial response was proportional to the change in QVR driving pressure. Changes in PAW generated volume shifts into and out of the right atrium, but their effect on upstream pressure was negligible. Our findings support the concept that RAP acts as backpressure to QVR and that Guyton's model of circulatory equilibrium qualitatively predicts the dynamic response from changing RAP.NEW & NOTEWORTHY Venous return responds immediately to changes in right atrial pressure. Concomitant volume shifts within the systemic circulation due to an imbalance between cardiac output and venous return have negligible effects on mean systemic filling pressure. Guyton's model of circulatory equilibrium can qualitatively predict the resulting changes in dynamic conditions with right atrial pressure as backpressure to venous return.

Relation of Right Atrial Volume, Systemic Venous Dimensions, and Flow Patterns to Right Atrial Pressure in Infants and Children.

Echocardiographic assessment of right atrial (RA) volume, inferior vena cava (IVC) diameter, and hepatic vein flow velocity independently correlate with the RA pressure by direct catheter measurement in adults. We prospectively collected invasive RA pressure measurements and echocardiographic data in infants and young children with the goal of developing a predictive model to noninvasively determine normal RA pressure. All subjects had a central venous catheter through which RA pressure could be transduced. Specific inclusion criteria consisted of (1) biventricular heart, (2) absence of inotropes, (3) sinus rhythm, and (4) at least 24 hours from surgery. Two-dimensional echocardiography (2DE)-Doppler and 3DE-Doppler were used to measure RA volume, systemic venous diameters, and flow velocity. Regression equations of RA pressure with RA volume, systemic venous size, and flow velocity were explored. Of 46 studies, 43 (93%) had echocardiograms adequate for analysis. RA pressure did not correlate with body surface area or age (p = 0.69, p = 0.87). The mean indexed RA volume by 3DE-Doppler was significantly higher than by 2DE (p <0.005). On multivariable analysis, only IVC systolic flow velocity and systolic 2D Simpson's derived indexed RA volume demonstrated significant independent correlation with RA pressure, resulting in the equation: RA pressure (mm Hg) = 7.35 - 0.0025 × IVC systolic flow velocity (cm/s) + 0.119 × indexed RA volume by systolic 2D Simpson's (ml/m2). RA pressure did not show correlation with systemic venous diameters or systolic and diastolic flow velocities in the SVC and hepatic veins. In conclusion, regression incorporating 2DE-derived RA volume and IVC systolic flow velocity provided the best noninvasive estimate of normal RA pressure in infants and children. The model derived requires validation in an independent sample.