The morbidity and mortality associated with preeclampsia is staggering. The physiology of the Page kidney, a condition in which increased intrarenal pressure causes hypertension, appears to provide a unifying framework to explain the complex pathophysiology. Page kidney hypertension is renin-mediated acutely and ischemia-mediated chronically.
View Article and Find Full Text PDFAtrioventricular valve replacement options are limited in infants and small children. The Melody stented bovine jugular vein conduit is being used with increasing frequency for percutaneous pulmonary valve replacement. The Melody valve can be serially dilated over time to accommodate the somatic growth of pediatric patients.
View Article and Find Full Text PDFNew evidence of increased phosphodiesterase-5 (PDE-5) in hypertrophied human myocardium suggests that sildenafil, a selective PDE-5 inhibitor, may improve muscle contraction and therefore improve ventricular function. The purpose of this study was to compare ventricular function as assessed by echocardiography in 10 surgically palliated single-ventricle patients at baseline and again after a single dose of sildenafil. The velocity time integral of the ventricular outflow tract was increased 2 h after sildenafil administration (p = 0.
View Article and Find Full Text PDFDespite the emerging relevance of high-density lipoprotein (HDL) in the inflammatory cascade and vascular barrier integrity, HDL levels in children undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL-cholesterol (HDL-C) in single-ventricle patients was quantified before and after the Fontan operation, and it was determined whether relationships existed between the duration and the type of postoperative pleural effusions. The study prospectively enrolled 12 children undergoing the Fontan operation.
View Article and Find Full Text PDFIn this study, we develop an innovative approach to rigorously quantify the evolving hemodynamic environment of the atrioventricular (AV) canal of avian embryos. Ultrasound generated velocity profiles were imported into Micro-Computed Tomography generated anatomically precise cardiac geometries between Hamburger-Hamilton (HH) stages 17 and 30. Computational fluid dynamic simulations were then conducted and iterated until results mimicked in vivo observations.
View Article and Find Full Text PDFComplications after cardiac surgery in neonates can occur because of activation of the inflammatory system. This study used lipopolysaccharide (LPS) endotoxin exposure to cause cytokine activation in neonatal mice and examine left ventricular (LV) function and the effects of antioxidant treatment on cytokine levels. Neonatal mice (6 d old) were injected with either 25 mg/kg LPS (n = 13) or PBS (n = 14), and LV function (echocardiography) was measured at 4 h.
View Article and Find Full Text PDFBackground: Surgery for congenital heart disease initiates a complex inflammatory response that can influence the postoperative course. However, broad integration of the cytokine and proteolytic cascades (matrix metalloproteinases: MMPs), which may contribute to postoperative outcomes, has not been performed.
Methods And Results: Using a low-volume (50-60 μL), high-sensitivity, multiplex approach, we serially measured a panel of cytokines (interleukins 2, 4, 6, 8, and 10, tumor necrosis factor alpha, interleukin 1β, and granulocyte-macrophage colony stimulating factor) and matrix metalloproteinases (matrix metalloproteinases 2, 3, 7, 8, 9, 12, and 13) in patients (n = 9) preoperatively and after repair of ventricular septal defect.
Background: After cardiopulmonary bypass (CPB), elaboration of cytokines, and subsequent induction of interstitial proteases, such as matrix metalloproteinases (MMPs), can result in a complex postoperative course. The serine protease inhibitor, aprotinin, which has been used in congenital heart surgery putatively for modulating fibrinolysis is now unavailable, necessitating the use of lysine analogues such as tranexamic acid (TXA). The present study tested the hypothesis that distinctly different plasma profiles of signaling molecules and proteases would be differentially affected after the administration of aprotinin or TXA in the context of congenital cardiac surgery and CPB.
View Article and Find Full Text PDFBackground: The concept of specifying positional information in the adult cardiovascular system is largely unexplored. While the Hox transcriptional regulators have to be viewed as excellent candidates for assuming such a role, little is known about their presumptive cardiovascular control functions and in vivo expression patterns.
Results: We demonstrate that conventional reporter gene analysis in transgenic mice is a useful approach for defining highly complex Hox expression patterns in the adult vascular network as exemplified by our lacZ reporter gene models for Hoxa3 and Hoxc11.
This article concerns the development of myocardial architecture--crucial for contractile performance of the heart and its conduction system, essential for generation and coordinated spread of electrical activity. Topics discussed include molecular determination of cardiac phenotype (contractile and conducting), remodeling of ventricular wall architecture and its blood supply, and relation of trabecular compaction to noncompaction cardiomyopathy. Illustrated are the structure and function of the tubular heart, time course of trabecular compaction, and development of multilayered spiral systems of the compact layer.
View Article and Find Full Text PDFHere we report that mouse embryos homozygous for a gene trap insertion in the fibulin-1 (Fbln1) gene are deficient in Fbln1 and exhibit cardiac ventricular wall thinning and ventricular septal defects with double outlet right ventricle or overriding aorta. Fbln1 nulls also display anomalies of aortic arch arteries, hypoplasia of the thymus and thyroid, underdeveloped skull bones, malformations of cranial nerves and hemorrhagic blood vessels in the head and neck. The spectrum of malformations is consistent with Fbln1 influencing neural crest cell (NCC)-dependent development of these tissues.
View Article and Find Full Text PDFThe chick embryo has long been a favorite model system for morphologic and physiologic studies of the developing heart, largely because of its easy visualization and amenability to experimental manipulations. However, this advantage is diminished after 5 days of incubation, when rapidly growing chorioallantoic membranes reduce visibility of the embryo. Using high-frequency ultrasound, we show that chick embryonic cardiovascular structures can be readily visualized throughout the period of Stages 9-39.
View Article and Find Full Text PDFEndocardial cushions are critical to maintain unidirectional blood flow under constantly increasing hemodynamic forces, but the interrelationship between endocardial cushion structure and the mechanics of atrioventricular junction function is poorly understood. Atrioventricular (AV) canal motions and blood velocities of embryonic chicks at Hamburger and Hamilton (HH) stages 17, 21, and 25 were quantified using ultrasonography. Similar to the embryonic zebrafish heart, the HH17 AV segment functions like a suction pump, with the cushions expanding in a wave during peak myocardial contraction and becoming undetectable during the relaxation phase.
View Article and Find Full Text PDFHemodynamics influence cardiac development, and alterations in blood flow may lead to impaired cardiac growth and malformations. The developing myocardium adapts to augmented workload by increasing cell number (hyperplasia). The aim of this study was to determine the influence of alterations in ventricular preload on fetal myocyte proliferation by manipulation of intracardiac shunting at the atrial level.
View Article and Find Full Text PDFGiven the tolerance of the right heart circulation to mild regurgitation and gradient, we study the potential of using motionless devices to regulate the pulmonary circulation. In addition, we document the flow performance of two mechanical valves. A motionless diode, a nozzle, a mechanical bileaflet valve, and a tilting disk valve were tested in a pulmonary mock circulatory system over the normal human range of pulmonary vascular resistance (PVR).
View Article and Find Full Text PDFA study of mechanical heart valve behavior in the pulmonary position as a function of pulmonary vascular resistance is reported for the St. Jude Medical bileaflet (SJMB) valve and the MedicalCV Omnicarbon (OTD) tilting disk valve. Tests were conducted in a pulmonic mock circulatory system and impedance was varied in terms of system pulmonary vascular resistance (PVR).
View Article and Find Full Text PDFRecent studies evaluating hematopoietic stem cell (HSC) potential raise the possibility that, in addition to embryonic sources, adult valve fibroblasts may be derived from HSCs. To test this hypothesis, we used methods that allow the potential of a single HSC to be evaluated in vivo. This was achieved by isolation and clonal expansion of single lineage-negative (Lin-), c-kit(+), Sca-1(+), CD34- cells from the bone marrow of mice that ubiquitously express enhanced green fluorescent protein (EGFP) combined with transplantation of individual clonal populations derived from these candidate HSCs into a lethally irradiated congenic non-EGFP mouse.
View Article and Find Full Text PDFHypoplastic left heart syndrome is a rare but serious form of congenital cardiac disease, characterized by underdevelopment of the components of the left heart, rendering the left ventricle non-functional. Its aetiology is largely unknown, but there is certainly a genetic component. Prenatal diagnosis nowadays uncovers about half of cases.
View Article and Find Full Text PDFBackground: The aim of this study is to compare hemodynamic status, in particular systemic oxygen delivery, in patients undergoing a Norwood procedure with a right ventricle-to-pulmonary artery (RV-PA) versus a modified Blalock-Taussig (mBT) shunt.
Methods: From June 2000 to November 2003, 44 consecutive neonates with hypoplastic left heart syndrome underwent a Norwood procedure. The first 25 patients received an mBT shunt; the subsequent 19 an RV-PA shunt.
A prenatal echocardiogram revealed a large right ventricular mass. Following birth, there was obstruction to pulmonary blood flow and cyanosis. The tumor's size and location prevented resection.
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