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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 (â¼40 s, n = 11), moderate (â¼2 min, n = 11) or extended (â¼5 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 (â¼40 s), moderate (â¼2 min) or extended (â¼5 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.
Assuntos
Canal Arterial , Hipertensão Pulmonar , Gravidez , Feminino , Ovinos , Animais , Clampeamento do Cordão Umbilical , Pulmão/irrigação sanguínea , Artéria Pulmonar/fisiologia , Canal Arterial/fisiologia , Perfusão , ConstriçãoRESUMO
PURPOSE OF REVIEW: This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions. RECENT FINDINGS: Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches. This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries.
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Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.
Assuntos
Artérias , Fotopletismografia , Humanos , Artérias/fisiologia , Fotopletismografia/métodos , Análise de Onda de Pulso , Modelos CardiovascularesRESUMO
BACKGROUND: Anorexia nervosa (AN) is associated with maladaptive cardiovascular changes. This study investigated whether individuals who recovered from AN during adolescence experience long-term cardiovascular risk in early adulthood. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospital Eating Disorder Services in Melbourne, Australia underwent cardiovascular testing. Measurements were performed using an oscillometric device for blood pressure and pulse wave velocity, ultrasound for carotid wall structure/function, resting electrocardiogram for heart-rate variability, and the EndoPat 2000 (Itamar) system for endothelial function. Patient measures were compared to healthy controls and/or normal thresholds. RESULTS: Ninety-one percent of the former AN patients (N = 22) and controls (N = 66) were female, aged approximately 25 years, with a healthy body mass index. The mean time interval from AN recovery to participation was 7.4 years. Pulse wave velocity was lower in the former AN patients than controls. Carotid intima-media thickness was not different; however, carotid distensibility and compliance were lower, and the elastic modulus higher in the former AN patients. Greater vagal tone was observed and endothelial dysfunction was evident in 46% of the former patients. CONCLUSIONS: Young adults who recovered from adolescent AN exhibit persistent cardiovascular adaptations. Routine cardiovascular monitoring could manage potential disease risk. IMPACT: Cardiovascular complications are common in patients with anorexia nervosa (AN) and population studies have revealed that developmental adaptations in response to undernutrition have long-term consequences for cardiovascular health. In this study of young adults treated for AN during adolescence, there was evidence of increased carotid artery stiffness, reduced aortic stiffness, vagal hyperactivity, and endothelial dysfunction in early adulthood when compared to healthy controls. It is important to consider the cardiovascular health of patients with AN beyond achieving medical stability. Interventions that monitor cardiovascular health could minimise the burden of future cardiovascular disease.
Assuntos
Anorexia Nervosa , Doenças Cardiovasculares , Rigidez Vascular , Criança , Adulto Jovem , Humanos , Feminino , Adolescente , Adulto , Idoso , Masculino , Análise de Onda de Pulso/efeitos adversos , Fatores de Risco , Anorexia Nervosa/complicações , Coração , Artérias Carótidas/diagnóstico por imagem , Doenças Cardiovasculares/etiologiaRESUMO
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.
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Artérias Carótidas , Hemodinâmica , Pressão Sanguínea , Diástole , Humanos , Sístole , Adulto JovemRESUMO
In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization.
Assuntos
Hemodinâmica/fisiologia , Modelos Cardiovasculares , Software , Síndrome de Alagille/fisiopatologia , Síndrome de Alagille/cirurgia , Vasos Sanguíneos/anatomia & histologia , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/fisiologia , Biologia Computacional , Simulação por Computador , Análise de Elementos Finitos , Fatores de Risco de Doenças Cardíacas , Humanos , Imageamento Tridimensional , Transplante de Fígado/efeitos adversos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Modelos Anatômicos , Modelagem Computacional Específica para o Paciente , Complicações Pós-Operatórias/etiologia , Interface Usuário-ComputadorRESUMO
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.
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Feto , Ventrículos do Coração , Animais , Animais Recém-Nascidos , Débito Cardíaco , Constrição , Feminino , Hemodinâmica , Humanos , OvinosRESUMO
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.
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Betametasona/farmacologia , Coração Fetal/efeitos dos fármacos , Glucocorticoides/farmacologia , Hemodinâmica/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Animais , Feminino , Coração Fetal/fisiopatologia , Idade Gestacional , Masculino , Fluxo Sanguíneo Regional , Carneiro DomésticoRESUMO
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.
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Líquidos Corporais , Ventrículos do Coração/embriologia , Pulmão/embriologia , Ovinos/embriologia , Animais , Ventrículos do Coração/fisiopatologia , Contração Miocárdica , Função Ventricular EsquerdaRESUMO
Extensive evidence shows that risk factors for cardiovascular disease (CVD) begin to develop early in life. Childhood obesity and elevated blood pressure (BP) have become overwhelmingly challenging, with 57% of today's children predicted to be obese by the age of 35 years, and global rates of hypertension in children and adolescents increasing by 75% from 2000 to 2015. Thus, there is an urgent need for tools that can assess early CVD risk in youth, which may lead to better risk stratification, preventative intervention, and personalised medicine. Vascular ageing (the deterioration in vascular structure and function) is a pivotal progenitor of health degeneration associated with elevated BP. Exposure to adverse environmental and genetic factors from fetal life promotes the development and accumulation of subclinical vascular changes that direct an individual towards a trajectory of early vascular ageing (EVA)-an independent predictor of target organ damage in the heart, brain, and kidneys. Therefore, characterising vascular ageing from youth may provide a window into cardiovascular risk later in life. However, vascular ageing measurements only have value when techniques are accurate/validated and when reliable thresholds are available for defining normal ranges and ranges that signal increased risk of disease. The aim of this paper is to summarise current evidence on the importance of vascular ageing assessment in youth and the impact of interventions to prevent or delay EVA, to highlight the need for standardisation and validation of measurement techniques in children and adolescents, and the importance of establishing reference values for vascular ageing measures in this population.
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Doenças Cardiovasculares , Hipertensão , Obesidade Infantil , Rigidez Vascular , Adolescente , Adulto , Envelhecimento , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Humanos , Fatores de RiscoRESUMO
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.
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Cardiopatias Congênitas , Tetralogia de Fallot , Transposição dos Grandes Vasos , Rigidez Vascular , Cardiopatias Congênitas/complicações , Humanos , Análise de Onda de Pulso , Tetralogia de Fallot/cirurgiaRESUMO
Current thinking suggests that wave reflection in arteries limits pulse pressure and hydraulic energy (HE) transmission to the microvasculature and that this protective effect reduces with advancing age. However, according to transmission line theory, pressure transmission (Tp) and reflection (R) coefficients are proportional (Tp = 1 + R), implying that wave reflection would promote rather than limit pressure transmission. We hypothesized that increasing distal pulse pressure (PPd) with age is instead related to increased proximal pulse pressure (PPp) and its forward component and that these are modulated by arterial compliance. A one-dimensional model of a fractal arterial tree containing 21 generations was constructed. Wave speed in each vessel was prescribed to achieve a uniform R at every junction, with changes in R achieved by progressively stiffening proximal or distal vessels. For both stiffening scenarios, decreasing reflection led to a decrease or no change in PPd when forward pressure or compliance were held constant, respectively, suggesting that wave reflection per se does not limit pressure transmission. Proximal pulse pressure, its forward component, and PPd increased with decreasing compliance; furthermore, proximal and distal pulse pressures were approximately proportional. With fixed compliance but decreasing reflection, HE transmission increased, whereas pressure transmission decreased, consistent with transmission line theory. In conclusion, wave reflection does not protect the microvasculature from high PPd; rather, PPp and PPd are modulated by arterial compliance, which reduces with age. Wave reflection has opposing effects on pressure and HE transmission; hence, the relative importance of pressure versus HE in contributing to microvascular damage warrants investigation.NEW & NOTEWORTHY With aging, a reduction in the stiffness gradient between elastic and muscular arteries is thought to reduce wave reflection in conduit arteries, leading to increased pulsatile pressure transmission into the microvasculature. This assumes that wave reflection limits pressure transmission in arteries. However, using a computational model, we showed that wave reflection promotes pulsatile pressure transmission, although it does limit hydraulic energy transmission. Increased microvascular pulse pressure with aging is instead related to decreasing arterial compliance.
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Envelhecimento/fisiologia , Artérias/fisiologia , Pressão Sanguínea , Microvasos/fisiologia , Modelos Cardiovasculares , Animais , Artérias/crescimento & desenvolvimento , Humanos , Microvasos/crescimento & desenvolvimento , Fluxo Pulsátil , Análise de Onda de PulsoRESUMO
OBJECTIVES: Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside. DESIGN: prospective single-center observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS: Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion. INTERVENTIONS: Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4-6 hours after milrinone infusion. MEASUREMENTS AND MAIN RESULTS: Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves-a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change. CONCLUSIONS: In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.
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Procedimentos Cirúrgicos Cardíacos/métodos , Cardiotônicos/uso terapêutico , Milrinona/uso terapêutico , Vasodilatadores/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiotônicos/administração & dosagem , Ecocardiografia , Feminino , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Lactente , Infusões Intravenosas , Masculino , Milrinona/administração & dosagem , Estudos Prospectivos , Vasodilatadores/administração & dosagem , Função Ventricular/efeitos dos fármacosRESUMO
As prior work has shown that reducing lung liquid volume 1) increases pulmonary arterial (PA) blood flow, 2) augments right ventricular (RV) output/power, and 3) decreases left atrial (LA) pressure, we tested the hypothesis that this perturbation has global cardiovascular effects. Ten anesthetized, open-chest fetal lambs (128 ± 2 days gestation, full term = 147 days) were acutely instrumented with 1) LA and right atrial (RA) catheters, 2) aortic and pulmonary trunk catheters, 3) brachiocephalic trunk, aortic isthmus, ductal, and left PA flow probes to obtain left ventricular (LV) and RV outputs and hydraulic power and flow in the descending thoracic aorta, and 4) an endotracheal tube to remove lung liquid. A 17 ± 7 ml/kg reduction of lung liquid volume 1) decreased LA and RA pressures similarly (1.5-1.6 mmHg, P < 0.001), 2) augmented LV and RV outputs (21-24%, P < 0.001) and total power (27-28%, P < 0.005), 3) increased systolic flows in the brachiocephalic trunk (18%, P < 0.001), aortic isthmus (29%, P < 0.005), ductus (12%, P < 0.005), and descending thoracic aorta (16%, P < 0.001), 4) increased mean PA flow via a higher systolic inflow (37%, P < 0.001) and lower diastolic backflow (-16%, P < 0.05), and 5) did not change systemic vascular conductance or arterial compliance but increased both pulmonary vascular conductance and arterial compliance (1.8-fold, P < 0.001). These data suggest that hemodynamic effects of lung liquid volume reduction are not confined to the lungs but extend to all cardiac chambers via rises in LV and RV outputs and power, despite falls in cardiac filling pressures, as well as the systemic circulation, via downstream increases in systolic flows of major central arteries.
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Artérias/fisiologia , Débito Cardíaco/fisiologia , Água Extravascular Pulmonar/fisiologia , Coração/fisiologia , Adulto , Animais , Animais Recém-Nascidos , Artérias/embriologia , Gasometria , Pressão Sanguínea , Feminino , Coração/embriologia , Ventrículos do Coração , Humanos , Gravidez , Artéria Pulmonar/fisiologia , Fluxo Sanguíneo Regional , Carneiro Doméstico , Resistência Vascular/fisiologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologiaRESUMO
The glucocorticosteroid betamethasone is routinely administered via maternal intramuscular injection to enhance fetal lung maturation before anticipated preterm birth. Although antenatal betamethasone increases fetal pulmonary arterial (PA) blood flow, whether this agent alters the contribution of 1) right ventricular (RV) output or 2) left-to-right shunting across the ductus arteriosus to rises in PA blood flow after preterm birth is unknown. To address this question, anesthetized control (n = 7) and betamethasone-treated (n = 7) preterm fetal lambs (gestation 127 ± 1 days, means ± SD) were instrumented with aortic, pulmonary, and left atrial catheters as well as ductus arteriosus and left PA flow probes to calculate RV output, with hemodynamics measured for 30 min after cord clamping and mechanical ventilation. Mean PA blood flow was higher in betamethasone-treated than in control lambs over the initial 10 min after birth (P < 0.05). This higher PA flow was accompanied by 1) a greater pulmonary vascular conductance (P ≤ 0.025), 2) a larger proportion of RV output passing to lungs (P ≤ 0.01), despite a fall in this output, and 3) earlier reversal and a greater magnitude (P ≤ 0.025) of net ductal shunting, due to the combination of higher left-to-right (P ≤ 0.025) and lesser right-to-left phasic shunting (P ≤ 0.025). These results suggest that antenatal betamethasone augments the initial rise in PA blood flow after birth in preterm lambs, with this augmented rise supported by the combination of 1) a greater redistribution of RV output toward the lungs and 2) a faster and larger reversal in net ductal shunting underpinned not only by greater left-to-right, but also by lesser right-to-left phasic shunting.
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Betametasona/administração & dosagem , Canal Arterial/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Pulmão/irrigação sanguínea , Nascimento Prematuro , Circulação Pulmonar/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Esquema de Medicação , Canal Arterial/fisiopatologia , Feminino , Idade Gestacional , Gravidez , Carneiro Doméstico , Fatores de TempoRESUMO
BACKGROUND: As surges in circulating norepinephrine and epinephrine have chronotropic, pressor, and inotropic effects, we tested the hypothesis that blunted rises in these catecholamines during preterm birth accompanied hemodynamic stability observed after early ventilation and delayed cord clamping (DCC), with findings compared to immediate cord clamping (ICC) and a non-asphyxial cord clamp-to-ventilation interval. METHODS: Anesthetized preterm fetal lambs were instrumented with arterial micromanometers to obtain pressure and the maximal rate of pressure rise (dP/dtmax) as a surrogate of ventricular contractility and an aortic catheter to obtain blood samples for catecholamine assay. Fetuses were delivered and mechanically ventilated before cord clamping â¼1.5 min later (DCC, n = 9) or subjected to ICC with ventilation started â¼40 s later (n = 8). RESULTS: Perinatal hemodynamics were stable after DCC, with greater fluctuations evident following birth after ICC (P ≤ 0.05). With DCC, circulating norepinephrine and epinephrine were unchanged after early ventilation but rose following cord clamping (P ≤ 0.01), with concentrations below the threshold for hemodynamic effects. Norepinephrine was higher in the ICC group after cord clamping and immediately after ventilation (P < 0.025), but catecholamine levels were otherwise similar between groups. CONCLUSION: Hemodynamic stability at birth after DCC is accompanied by sub-threshold rises in circulating norepinephrine and epinephrine and thus blunted sympathoadrenal activation.
Assuntos
Epinefrina/sangue , Norepinefrina/sangue , Cordão Umbilical , Medula Suprarrenal/metabolismo , Animais , Pressão Sanguínea , Catecolaminas/metabolismo , Constrição , Feminino , Frequência Cardíaca , Hemodinâmica , Masculino , Parto , Ventilação Pulmonar , Respiração Artificial , Ovinos , Sistema Nervoso SimpáticoRESUMO
Multi-beat end-systolic elastance (EMB) is considered a gold-standard index of ventricular contractility. However, it is difficult to measure clinically due to the need for transient manipulation of ventricular preload or afterload. We compared the performance of 5 'single-beat' methods that do not require loading interventions, for estimating the equivalent of EMB. In 7 sheep instrumented with a micromanometer/conductance catheter, single-beat methods were compared with EMB, obtained after transiently decreasing preload or increasing afterload under a broad range of heart rates and inotropic conditions. The single-beat elastance (ESB) method described by Shishido et al. (Circulation 102(16):1983-1989, 2000) had the highest correlation (R = 0.69, y = 0.52x + 0.43) with EMB, although the absolute accuracy was poor. Interestingly, for all methods tested, a higher correlation was observed when EMB was obtained with an afterload increase (R = 0.47 - 0.78) rather than a preload reduction (R = 0.07-0.57). Within-animal regression coefficients were higher than those obtained from pooled data, with excellent within-animal correlation observed for Shishido et al. method (0.73 ≤ R ≤ 0.96) when using afterload increase as the loading intervention. We conclude that (1) current methods perform better when using an afterload increase to obtain reference EMB, (2) intra-individual ESB comparisons may be more reliable than inter-individual comparisons and (3) Shishido et al.'s method demonstrated the strongest correlation with EMB. Current ESB methods have limited and variable accuracy, but may hold promise for tracking relative changes in ventricular contractility in individuals.
Assuntos
Frequência Cardíaca/fisiologia , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Animais , Masculino , Modelos Animais , OvinosRESUMO
BACKGROUND: Twenty-four-hour (24-hr) ambulatory blood pressure monitoring (ABPM) is often considered the gold standard to detect hypertension. We aimed to determine the short-term progression of 24-hour blood pressure after coarctation repair and to compare ABPM between two different devices. METHODS: We performed a cross-sectional study using 24-hour ABPM (Oscar 2) in 47 patients aged 16-48 years with previous paediatric coarctation repair and not on antihypertensive medication. Results were compared to a previous ABPM using paired analyses. A subset (10/47, 21%) had an additional previous ABPM performed using a Spacelabs device. RESULTS: After a mean follow-up of 27±6 years after repair, hypertension and prehypertension on Oscar 2 ABPM was present in 57% (27/47) and 11% (5/47), respectively. Mean follow-up time between Oscar 2 ABPMs was 3.9±1.4 years, and between first Oscar 2 and Spacelabs and between Spacelabs and second Oscar 2 ABPM was 1.4±0.8 and 1.8±0.3 years, respectively. There was no difference in the proportion of hypertensive patients between Oscar 2 ABPMs (55% [26/47] vs. 57% [27/47], p=1.0) but 17 patients (17/47, 36%) had a reclassification of 24-hour ABPM status. Mean 24-hour systolic blood pressure was higher in both Oscar 2 ABPMs compared to Spacelabs (142.4±11.7 vs. 120.4±11.8mmHg, p=0.0001; and 137.4±12.2 vs. 120.4±11.8mmHg, p=0.0001; respectively). CONCLUSION: There was high intra-device reproducibility of 24-hour ABPM results using an Oscar 2 device but poor inter-device reproducibility in patients with repaired coarctation. Device-specific reference values may be required to ensure reliable 24-hour ABPM interpretation.
Assuntos
Anti-Hipertensivos/administração & dosagem , Coartação Aórtica , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Hipertensão , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto , Coartação Aórtica/fisiopatologia , Coartação Aórtica/cirurgia , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/fisiopatologia , Reprodutibilidade dos TestesRESUMO
KEY POINTS: Coronary wave intensity analysis (WIA) is an emerging technique for assessing upstream and downstream influences on myocardial perfusion. It is thought that a dominant backward decompression wave (BDWdia ) is generated by a distal suction effect, while early-diastolic forward decompression (FDWdia ) and compression (FCWdia ) waves originate in the aorta. We show that wave reflection also makes a substantial contribution to FDWdia , FCWdia and BDWdia , as quantified by a novel method. In 18 sheep, wave reflection accounted for â¼70% of BDWdia , whereas distal suction dominated in a computer model representing a hypertensive human. Non-linear addition/subtraction of mechanistically distinct waves (e.g. wave reflection and distal suction) obfuscates the true contribution of upstream and downstream forces on measured waves (the 'smoke and mirrors' effect). The mechanisms underlying coronary WIA are more complex than previously thought and the impact of wave reflection should be considered when interpreting clinical and experimental data. ABSTRACT: Coronary arterial wave intensity analysis (WIA) is thought to provide clear insight into upstream and downstream forces on coronary flow, with a large early-diastolic surge in coronary flow accompanied by a prominent backward decompression wave (BDWdia ), as well as a forward decompression wave (FDWdia ) and forward compression wave (FCWdia ). The BDWdia is believed to arise from distal suction due to release of extravascular compression by relaxing myocardium, while FDWdia and FCWdia are thought to be transmitted from the aorta into the coronary arteries. Based on an established multi-scale computational model and high-fidelity measurements from the proximal circumflex artery (Cx) of 18 anaesthetized sheep, we present evidence that wave reflection has a major impact on each of these three waves, with a non-linear addition/subtraction of reflected waves obscuring the true influence of upstream and downstream forces through concealment and exaggeration, i.e. a 'smoke and mirrors' effect. We also describe methods, requiring additional measurement of aortic WIA, for unravelling the separate influences of wave reflection versus active upstream/downstream forces on coronary waves. Distal wave reflection accounted for â¼70% of the BDWdia in sheep, but had a lesser influence (â¼25%) in the computer model representing a hypertensive human. Negative reflection of the BDWdia at the coronary-aortic junction attenuated the Cx FDWdia (by â¼40% in sheep) and augmented Cx FCWdia (â¼5-fold), relative to the corresponding aortic waves. We conclude that wave reflection has a major influence on early-diastolic WIA, and thus needs to be considered when interpreting coronary WIA profiles.