ABSTRACT
The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular-vascular uncoupling and adverse ventricular-ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force-specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.
Subject(s)
Aorta/physiopathology , Hemodynamics , Pulmonary Artery/physiopathology , Pulmonary Heart Disease/physiopathology , Vascular Remodeling , Animals , Aorta/metabolism , Aorta/pathology , Arterial Pressure/physiology , Cell Proliferation , Coronary Occlusion/genetics , Coronary Occlusion/metabolism , Coronary Occlusion/physiopathology , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Fetus , Heart Ventricles/metabolism , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Humans , Lung/metabolism , Lung/pathology , Lung/physiopathology , Nitric Oxide/metabolism , Pregnancy , Primary Cell Culture , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Pulmonary Circulation/physiology , Pulmonary Heart Disease/congenital , Pulmonary Heart Disease/metabolism , Pulmonary Heart Disease/pathology , SheepABSTRACT
In an anatomic study of 21 cases of pulmonary atresia with tricuspid insufficiency (pulmonary atresia with intact ventricular septum, type II), the morphologic features of the tricuspid valve and the right ventricle were found to differ greatly from those seen in pulmonary atresia with tricuspid stenosis (pulmonary atresia with intact ventricular septum, type I). Morphologically, pulmonary atresia with tricuspid insufficiency (type II) has a greater resemblance to Ebstein's disease with pulmonary atresia than to type I pulmonary atresia. The anomaly may be more amenable to surgery than pulmonary atresia with tricuspid stenosis because the right ventricle in the former may be converted into a functional chamber by a valvotomy combined with a shunting procedure and atrial septostomy.
Subject(s)
Pulmonary Heart Disease/pathology , Tricuspid Valve Insufficiency/pathology , Female , Heart Atria/pathology , Heart Ventricles/pathology , Humans , Infant , Infant, Newborn , Male , Pulmonary Heart Disease/congenital , Pulmonary Valve/pathology , Tricuspid Valve/pathologyABSTRACT
We report an infant with a bronchiolitis-like illness and rapid deterioration who developed a cor pulmonale-like picture with a dilated right ventricle. Urinary organic acid assays established a probable diagnosis of Cbl-C-type methylmalonic aciduria, later confirmed by complementation studies. Despite medical intervention and cyanocobalamin treatment the patient died on his tenth hospital day. Postmortem examination showed the presence of thromboemboli in the pulmonary circulation. We hypothesize that acute cor pulmonale developed in this infant secondary to thromboembolism of his pulmonary circulation. A review of the literature shows that thromboembolism may be a part of this disease process.
Subject(s)
Homocystinuria/complications , Malonates/blood , Methylmalonic Acid/blood , Pulmonary Heart Disease/complications , Heart Ventricles/pathology , Homocystinuria/pathology , Humans , Infant , Male , Postmortem Changes , Pulmonary Embolism/complications , Pulmonary Embolism/congenital , Pulmonary Embolism/pathology , Pulmonary Heart Disease/congenitalSubject(s)
Heart Septal Defects, Atrial/therapy , Transposition of Great Vessels/therapy , Tricuspid Valve Stenosis/therapy , Angiocardiography , Assisted Circulation , Cardiac Catheterization/instrumentation , Child , Child, Preschool , Follow-Up Studies , Heart Defects, Congenital/therapy , Humans , Infant , Infant, Newborn , Methods , Palliative Care , Pulmonary Heart Disease/congenital , Pulmonary Heart Disease/mortality , Transposition of Great Vessels/mortality , Tricuspid Valve Stenosis/congenital , Tricuspid Valve Stenosis/mortalityABSTRACT
This article discusses structural congenital heart disease in the newborn. Emphasis is given to the clinical and laboratory diagnosis including the indication for cardiac catheterization and angiography. The discussion includes the group of cyanotic, noncyanotic and other structural congenital heart diseases, as well as the group of neonatal cardiopulmonary distress without structural heart disease. An outline of the general management of these entities is included in the presentation.