Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40 s, n = 11), moderate (∼2 min, n = 11) or extended (∼5 min, n = 12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P = 0.005) that persisted for 4 min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40 s), moderate (∼2 min) or extended (∼5 min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.

Superiority of a Representative MRI Flow Waveform over Doppler Ultrasound for Aortic Wave Reflection Assessment in Children and Adolescents With/Without a History of Heart Disease.

Wave separation analysis (WSA) reveals the impact of forward- and backward-running waves on the arterial pressure pulse, but the calculations require a flow waveform. This study investigated (1) the variability of the ascending aortic flow waveform in children and adolescents with/without a childhood heart disease history (CHD); (2) the accuracy of WSA obtained with a representative flow waveform (RepFlow), compared with the triangulation method and published ultrasound-derived adult representative flow; (3) the impact of limitations in Doppler ultrasound on WSA; and (4) generalizability of results to adults with a history of CHD. Phase contrast MRI was performed in youth without (n = 45, Group 1, 10-19 years) and with CHD (n = 79, Group 2, 7-18 years), and adults with CHD history (n = 29, Group 3, 19-59 years). Segmented aortic cross-sectional area was used as a surrogate for the central pressure waveform in WSA. A subject-specific virtual Doppler ultrasound was performed on MRI data by extracting velocities from a sample volume. Time/amplitude-normalized ascending aortic flow waveforms were highly consistent amongst all groups. WSA with RepFlow therefore yielded errors < 10% in all groups for reflected wave magnitude and return time. Absolute errors were typically 1.5-3 times greater with other methods, including subject-specific (best-case/virtual) Doppler ultrasound, for which velocity profile skewing introduced waveform errors. Our data suggest that RepFlow is the optimal approach for pressure-only WSA in children and adolescents with/without CHD, as well as adults with CHD history, and may even be more accurate than subject-specific Doppler ultrasound in the ascending aorta.

From fetus to neonate: A review of cardiovascular modeling in early life.

Computational modeling has well-established utility in the study of cardiovascular hemodynamics, with applications in medical research and, increasingly, in clinical settings to improve the diagnosis and treatment of cardiovascular diseases. Most cardiovascular models developed to date have been of the adult circulatory system; however, the perinatal period is unique as cardiovascular physiology undergoes drastic changes from the fetal circulation, during the birth transition, and into neonatal life. There may also be further complications in this period: for example, preterm birth (defined as birth before 37 completed weeks of gestation) carries risks of short-term cardiovascular instability and is associated with increased lifetime cardiovascular risk. Here, we review computational models of the cardiovascular system in early life, their applications to date and potential improvements and enhancements of these models. We propose a roadmap for developing an open-source cardiovascular model that spans the fetal, perinatal, and postnatal periods. This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Congenital Diseases > Computational Models.

Novel Centroid Method for Robust Evaluation of Return Time of Reflected Waves in the Systemic Arterial Network.

GOAL: A diastolic-to-systolic shift in the return time (RT) of backward waves to central arteries is expected with ageing. However, current methods of estimating RT-inflection point, zero crossing, and foot-depend on a single waveform feature and produce systolic RT throughout life. We propose a novel centroid method that accounts for the entire backward pressure waveform. We assess the accuracy of the various methods against a ground truth RT (GTRT) and their sensitivity to diastolic/systolic RT. METHODS: Linear wave tracking was implemented in a one-dimensional systemic arterial tree model and GTRT was calculated as the amplitude-weighted mean RT of backward waves at the ascending aorta. The sensitivity of the methods to diastolic/systolic RT was also assessed in ten sheep. A balloon catheter in the descending thoracic aorta generated a backward-running pulse that arrived at the ascending aorta at different times during diastole or systole, allowing the 'bulk' RT of the backward-running wave ensemble to be manipulated. RESULTS: Using a virtual cohort of 1200 patients, the centroid RT was closest to GTRT compared to the zero crossing, inflection point, and foot methods; mean differences (limits of agreement) were -8 (-47, 30), vs -42 (-136, 52), -78 (-305, 149), and -197 (-379,-15) ms, respectively. Furthermore, only the centroid method was sensitive to both diastolic and systolic RT; other methods were only sensitive to systolic RT. CONCLUSION: The centroid method had the highest accuracy and robustness in estimating RT. SIGNIFICANCE: This can provide insight into the diastolic-to-systolic shift in RT of backward waves with ageing.

Optimized design of an arterial network model reproduces characteristic central and peripheral haemodynamic waveform features of young adults.

The arterial network in healthy young adults is thought to be structured to optimize wave reflection in the arterial system, producing an ascending aortic pressure waveform with three key features: early systolic peak, negative systolic augmentation and diastolic hump. One-dimensional computer models have provided significant insights into arterial haemodynamics, but no previous models of the young adult have exhibited these three features. Given that this issue was likely to be related to unrepresentative or non-optimized impedance properties of the model arterial networks, we developed a new 'YoungAdult' model that incorporated the following features: (i) a new and more accurate empirical equation for approximating wave speeds, based on area and relative distance to elastic-muscular arterial transition points; (ii) optimally matched arterial junctions; and (iii) an improved arterial network geometry that eliminated 'within-segment' taper (which causes wave reflection in conduit arteries) whilst establishing 'impedance-preserving' taper. These properties of the model led to wave reflection occurring predominantly at distal vascular beds, rather than in conduit arteries. The model predicted all three typical characteristics of an ascending aortic pressure waveform observed in young adults. When compared with non-invasively acquired pressure and velocity measurements (obtained via tonometry and Doppler ultrasound in seven young adults), the model was also shown to reproduce the typical waveform morphology observed in the radial, brachial, carotid, temporal, femoral and tibial arteries. The YoungAdult model provides support for the concept that the arterial tree impedance in healthy young adults is exquisitely optimized, and it provides an important baseline model for investigating cardiovascular changes in ageing and disease states. KEY POINTS: The origin of wave reflection in the arterial system is controversial, but reflection properties are likely to give rise to characteristic haemodynamic features in healthy young adults, including an early systolic peak, negative systolic augmentation and diastolic hump in the ascending aortic pressure waveform, and triphasic velocity profiles in peripheral arteries. Although computational modelling provides insights into arterial haemodynamics, no previous models have predicted all these features. An established arterial network model was optimized by incorporating the following features: (i) a more accurate representation of arterial wave speeds; (ii) precisely matched junctions; and (iii) impedance-preserving tapering, thereby minimizing wave reflection in conduit arteries in the forward direction. Comparison with in vivo data (n = 7 subjects) indicated that the characteristic waveform features in young adults were predicted accurately. Our findings strongly imply that a healthy young arterial system is structured to optimize wave reflection in the main conduit arteries and that reflection of forward waves occurs primarily in the vicinity of vascular beds.

Inter-arm differences in regional arterial stiffness and geometry lead to inter-arm systolic blood pressure differences: A modelling study.

An inter-arm systolic blood pressure difference (ISBPD), if substantial in magnitude (typically defined as ≥10 mmHg), is a potential cardiovascular risk factor in adults, due to its association with cardiovascular events/mortality. A substantial ISBPD occurs in approximately 10% of the adult population, and, although associations with vascular disease and elevated stiffness have been reported, the mechanisms underlying ISBPD remain unknown. The aim of this study was to investigate whether inter-arm differences in segmental pulse wave velocity, cross-sectional area, or vascular bed compliance/resistance could give rise to substantial differences in brachial pressures between arms; for example, due to differences in pulse wave transmission and reflection. Using an established one-dimensional model of the major systemic arteries, pulse wave velocity (PWV) was uniformly increased or decreased in arteries of 1) the supra-aortic region leading up to the arm, 2) the brachial region, 3) the forearm, and 4) all of these (entire arm pathway); for the left arm, right arm, and both arms. Cross-sectional area and vascular bed compliance and resistance of the arms were similarly varied. Inter-arm differences in segmental PWV and cross-sectional area (but not bilateral changes) led to associated substantial inter-arm SBP differences, which were observed with changes to brachial, forearm and/or entire arm pathways and were related to altered transmission of forward waves and amplitude/timing of reflected waves. Vascular bed compliance and resistance had minimal influence. We conclude that inter-arm differences in arterial stiffness and geometry may contribute to inter-arm systolic blood pressure differences, warranting further investigation.

Divergent effects of initial ventilation with delayed cord clamping on systemic and pulmonary arterial flows in the birth transition of preterm lambs.

A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC followed by an asphyxial (∼2 min) cord clamp-to-ventilation (CC-V) interval. More recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45 s) CC-V interval, but it is unknown how ventricular output and central arterial blood flow effects of DCC compare with those of non-asphyxial ICC. Anaesthetized preterm fetal lambs instrumented with flow probes on major central arteries were ventilated for 97 (7) s (mean (SD)) before DCC at birth (n = 10), or underwent ICC 40 (6) s before ventilation (n = 10). Compared to ICC, initial ventilation and DCC was accompanied by (1) redistribution of a similar level of ascending aortic flow away from cephalic arteries and towards the aortic isthmus after ventilation; (2) a lower right ventricular output after cord clamping that was redistributed towards the lungs, thereby maintaining the absolute contribution of this output to a similar increase in pulmonary arterial flow after birth; and (3) a lower descending thoracic aortic flow after birth, related to a more rapid decline in phasic right-to-left ductal flow only partially offset by increased aortic isthmus flow. However, systemic arterial flows were similar between DCC and non-asphyxial ICC within 5 min after birth. These findings suggest that compared to non-asphyxial ICC, initial ventilation with DCC transiently redistributed central arterial flows, resulting in lower perinatal systemic arterial, but not pulmonary arterial, flows. KEY POINTS: A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC with an asphyxial (∼2 min) cord clamp-to-ventilation (CC-V) interval. Recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45 s) CC-V interval, but how central arterial blood flow effects of DCC compare with those of non-asphyxial ICC is unknown. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent initial ventilation for ∼90 s before DCC at birth, or ICC for ∼40 s before ventilation. Compared to non-asphyxial ICC, initial ventilation with DCC redistributed central blood flows, resulting in lower systemic, but not pulmonary, arterial flows during this period of transition. This flow redistribution was transitory, however, with systemic arterial flows similar between DCC and non-asphyxial ICC within minutes after birth.

S-Nitrosoglutathione Limits Apoptosis and Reduces Pulmonary Vascular Dysfunction After Bypass.

BACKGROUND: During hypoxia or acidosis, S-nitrosoglutathione (GSNO) has been shown to protect the cardiomyocyte from ischemia-reperfusion injury. In a randomized double-blinded control study of a porcine model of paediatric cardiopulmonary bypass (CPB), we aimed to evaluate the effects of 2 different doses (low and high) of GSNO. METHODS: Pigs weighing 15-20 kg were exposed to CPB with 1 hour of aortic cross-clamp. Prior to and during CPB, animals were randomized to receive low-dose (up to 20 nmol/kg/min) GSNO (n = 8), high-dose (up to 60 nmol/kg/min) GSNO (n = 6), or normal saline (n = 7). Standard cardiac intensive care management was continued for 4 hours post-bypass. RESULTS: There was a reduction in myocyte apoptosis after administration of GSNO (P = .04) with no difference between low- and high-dose GSNO. The low-dose GSNO group had lower pulmonary vascular resistance post-CPB (P = .007). Mitochondrial complex I activity normalized to citrate synthase activity was higher after GSNO compared with control (P = .02), with no difference between low- and high-dose GSNO. CONCLUSIONS: In a porcine model of CPB, intravenous administration of GSNO limits myocardial apoptosis through preservation of mitochondrial complex I activity, and improves pulmonary vascular resistance. There appears to be a dose-dependent effect to this protection.

Arterial Stiffness in Congenital Heart Disease.

Transposition of the great arteries (TGA), coarctation of the aorta (CoA), single ventricle (SV) and tetralogy of Fallot (ToF) are forms of congenital heart disease (CHD). Despite advances in treatment, cardiovascular and cerebrovascular complications in patients with repaired CHD occur earlier in life compared to healthy subjects. A factor that may contribute to this increased risk is elevated arterial stiffness. This systematic review provides a critical assessment of current evidence on central arterial stiffness in patients with CHD compared to healthy controls. In July 2020, Medline OVID, EMBASE and Scopus were searched using keywords and MeSH terms. Articles were included if they reported indices of aortic or carotid artery stiffness in patients with TGA, CoA, SV or ToF, and compared these to controls. Additional studies were screened from the reference lists of included articles. Of 1,033 studies identified, 43 were included in the final review. Most studies identified at least one index of central arterial stiffness, commonly in the aortic root or ascending aorta, that was higher in patients with CHD compared to controls. The commonly reported surrogate markers of stiffness were pulse wave velocity, aortic distensibility and the ß stiffness index. There was a relatively small number of original studies, and synthesis of data was limited by methodological heterogeneity, highlighting the need for further studies with standardised methods. However, there was consistent evidence of early and/or accelerated arterial stiffening in CHD patients, which may contribute to the increased risk of adverse cardiovascular and cerebrovascular events in this population.

Characteristics and physiological basis of falls in ventricular outputs after immediate cord clamping at delivery in preterm fetal lambs.

KEY POINTS: Controversy exists about the physiological mechanism(s) underlying decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, the four major determinants of ventricular output (afterload, preload, heart rate and contractility) were measured concurrently in fetal lambs at 15 s intervals over a 2 min period after cord clamping and before ventilation following delivery. After cord clamping, right (but not left) ventricular output fell by 20% in the initial 30 s, due to increased afterload associated with higher arterial blood pressures, but both outputs then halved over 45 s, due to a falling heart rate and deteriorating ventricular contractility accompanying rapid declines in arterial oxygenation to asphyxial levels. Ventricular outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in ventricular contractility accompanying asphyxia-induced surges in circulating catecholamines. These findings provide a physiological basis for the clinical recommendation that effective ventilation should occur within 60 s after immediate cord clamping. ABSTRACT: Controversy exists about the physiological mechanism(s) underlying large decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, anaesthetized preterm fetal lambs (127(1)d, n = 12) were instrumented with flow probes and catheters in major central arteries, and a left ventricular (LV) micromanometer-conductance catheter. Following immediate cord clamping at delivery, haemodynamics, LV and right ventricular (RV) outputs, and LV contractility were measured at 15 s intervals during a 2 min non-ventilatory period, with aortic blood gases and circulating catecholamine (noradrenaline and adrenaline) concentrations measured at 30 s intervals. After cord clamping, (1) RV (but not LV) output fell by 20% in the initial 30 s, due to a reduced stroke volume associated with increased arterial blood pressures, (2) both outputs then halved over the next 45 s, associated with falls in heart rate, arterial blood pressures and ventricular contractility accompanying a rapid decline in arterial oxygenation to asphyxial levels, (3) reduced outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in blood pressures and ventricular contractility accompanying exponential surges in circulating catecholamines. These findings are consistent with a time-dependent decline of ventricular outputs after immediate cord clamping, which comprised (1) an initial, minor fall in RV output related to altered loading conditions, (2) ensuing large decreases in both LV and RV outputs related to the combination of bradycardia and ventricular dysfunction during emergence of an asphyxial state, and (3) subsequent stabilization of reduced LV and RV outputs during ongoing asphyxia, supported by cardiovascular stimulatory effects of marked sympathoadrenal activation.

Assessment of diastolic blood pressure with the auscultatory method in children and adolescents under exercise conditions.

Controversy surrounds whether to define resting diastolic blood pressure (DBP) as the onset of the fourth or fifth Korotkoff phase (K4, sound muffling, or K5, sound disappearance) in children and adolescents. Although undetectable in some children (due to sounds continuing to zero cuff pressure), K5 is currently recommended for consistency with adult practice and because K4 can be difficult to discern or undetectable. However, to our knowledge, no studies have specifically assessed the reliability of measuring DBP with K4 and K5 in children and adolescents under exercise conditions. We therefore measured DBP before and immediately after a Bruce protocol stress test in 90 children and adolescents aged 12.3 ± 3.5 years (mean ± SD) in a cardiology clinic setting. When detected, K4 and K5 were 63.5 ± 9.2 and 60.2 ± 12.6 mmHg, respectively, at rest and 59.2 ± 14.6 mmHg (p = 0.028 vs rest) and 52.9 ± 18.3 mmHg (p < 0.001), respectively, immediately post-exercise. K4 and K5 were not detected in 41% and 4% of participants at rest or in 29% and 37% post-exercise, respectively, while K5 resulted in unrealistic DBP values (<30 mmHg) in an additional 11%. Better exercise performance was associated with a more frequent absence of K5 post-exercise, and after excluding participants performing at <10th percentile for age, post-exercise K4 was absent in 23%, and plausible K5 values were not obtained in 59% (p < 0.001). Although neither K4 nor K5 alone were reliable measures of DBP immediately post-exercise, a novel hybrid approach using K4, if detected, or K5, if not, produced reasonable DBP measurements in 97% of participants.

Magnitude and significance of interarm blood pressure differences in children and adolescents.

BACKGROUND: An interarm difference (IAD) in blood pressure (BP) of 10 mmHg or more is a potential cardiovascular risk factor in adults, given its association with cardiovascular events/mortality. In children and adolescents, accurate BP assessment is critical for identifying risk of end organ damage. However, IAD has not been systematically studied in paediatric patients; if present and of significant magnitude, measuring BP in only one arm could lead to misclassification of hypertensive status. METHOD: In 95 children/adolescents with a normal aorta (including 15 with a history of tetralogy of Fallot) aged 7-18 years attending the Royal Children's Hospital, Melbourne, we aimed to determine the magnitude of IAD, frequency of IAD of at least 10 mmHg, difference in BP classification between arms, and influence of repeat measures on IAD in a single visit. After 5 min rest, simultaneous bilateral BP was measured in triplicate with an automated device. RESULTS: Absolute systolic IAD was 5.0 mmHg (median, interquartile range 2-8 mmHg) and was 10 mmHg or more in 14%, with no change on repeat measures. In patients with a history of aortic surgery, IAD of 10 mmHg or more occurred in 27% (transposition of the great arteries, n = 15) and 75% (aortic coarctation, n = 8). Differences in BP classification, based on initial left vs. right arm measures, occurred in 25% (normal aorta) and 40%/63% (aortic surgery), or 17% and 33%/50%, respectively if second and third measurements were averaged. CONCLUSION: Substantial interarm BP differences were common, even in apparently healthy children and adolescents: evaluation of IAD may, therefore, be important for BP classification in the paediatric setting.

Antenatal betamethasone redistributes central blood flows and preferentially augments right ventricular output and pump function in preterm fetal lambs.

The glucocorticosteroid betamethasone, which is routinely administered prior to anticipated preterm birth to enhance maturation of the lungs and the cardiovascular system, has diverse fetal regional blood flow effects ranging from increased pulmonary flow to decreased cerebral flow. The aim of this study was to test the hypothesis that these diverse effects reflect alterations in major central flow patterns that are associated with complementary shifts in left ventricular (LV) and right ventricular (RV) pumping performance. Studies were performed in anesthetized preterm fetal lambs (gestation = 127 ± 1 days, term = 147 days) with (n = 14) or without (n = 12) preceding betamethasone treatment via maternal intramuscular injection. High-fidelity central arterial blood pressure and flow signals were obtained to calculate LV and RV outputs and total hydraulic power. Betamethasone therapy was accompanied by 1) increased RV, but not LV, output; 2) a greater RV than LV increase in total power; 3) a redistribution of LV output away from the fetal upper body region and toward the lower body and placenta; 4) a greater proportion of RV output passing to the lungs, and a lesser proportion to the lower body and placenta; and 5) a change in the relative contribution of venous streams to ventricular filling, with the LV having increased pulmonary venous and decreased foramen ovale components, and the RV having lesser superior vena caval and greater inferior vena caval portions. Taken together, these findings suggest that antenatal betamethasone produces a widespread redistribution of central arterial and venous flows in the fetus, accompanied by a preferential rise in RV pumping performance.

Reducing lung liquid volume in fetal lambs decreases ventricular constraint.

BACKGROUND: This study evaluated whether an increased left ventricular (LV) pump function accompanying reduction of lung liquid volume in fetal lambs was related to increased LV preload, augmented LV contractility, or both. METHODS: Eleven anesthetized preterm fetal lambs (gestation 128 ± 2 days) were instrumented with (1) an LV micromanometer-conductance catheter to obtain LV end-diastolic volume (EDV) and end-diastolic pressure (EDP), the maximal rate of rise of LV pressure (dP/dtmax), LV output, LV stroke work, and LV end-systolic elastance (Ees), a relatively load-independent measure of contractility; (2) an endotracheal tube to measure mean tracheal pressure and to reduce lung liquid volume. LV transmural pressure was calculated as LV EDP minus tracheal pressure. RESULTS: Reducing lung liquid volume by 16 ± 4 ml kg-1 (1) augmented LV output (by 16%, P = 0.001) and stroke work (29%, P < 0.001), (2) increased LV EDV (12%, P < 0.001), (3) increased LV transmural pressure (2.2 mmHg, P < 0.001), (4) did not change LV dP/dtmax normalized for EDV (P > 0.7), and (5) decreased LV Ees (20%, P < 0.01). CONCLUSION: These findings suggest a rise in LV pump function evident after reduction of lung liquid volume in fetal lambs was related to increased LV preload secondary to lessening of external LV constraint, without any associated rise in LV contractility. IMPACT: This study has shown that reducing the volume of liquid filling the fetal lungs lessens the degree of external constraint on the heart. This lesser constraint permits a rise in left ventricular dimensions and thus greater cardiac filling that leads to increased left ventricular pumping performance. This study has defined a mechanism whereby a reduction in lung liquid volume results in enhanced pumping performance of the fetal heart. These findings suggest that a reduction in lung liquid volume which occurs during the birth transition contributes to increases in left ventricular dimensions and pumping performance known to occur with birth.

Measurement, Analysis and Interpretation of Pressure/Flow Waves in Blood Vessels.

The optimal performance of the cardiovascular system, as well as the break-down of this performance with disease, both involve complex biomechanical interactions between the heart, conduit vascular networks and microvascular beds. 'Wave analysis' refers to a group of techniques that provide valuable insight into these interactions by scrutinizing the shape of blood pressure and flow/velocity waveforms. The aim of this review paper is to provide a comprehensive introduction to wave analysis, with a focus on key concepts and practical application rather than mathematical derivations. We begin with an overview of invasive and non-invasive measurement techniques that can be used to obtain the signals required for wave analysis. We then review the most widely used wave analysis techniques-pulse wave analysis, wave separation and wave intensity analysis-and associated methods for estimating local wave speed or characteristic impedance that are required for decomposing waveforms into forward and backward wave components. This is followed by a discussion of the biomechanical phenomena that generate waves and the processes that modulate wave amplitude, both of which are critical for interpreting measured wave patterns. Finally, we provide a brief update on several emerging techniques/concepts in the wave analysis field, namely wave potential and the reservoir-excess pressure approach.