Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling.

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.

Vasodilator Agents in Pediatric Cardiac Surgery with Cardiopulmonary Bypass

Surgical management of congenital heart disease has become regularly performed in tertiary hospitals worldwide. Although routinely needed, cardiopulmonary bypass (CPB) deleteriously affects physiological processes being among the main causes of increased morbidity in cardiac surgery, especially in neonates and children.Recent studies have shown that vasodilator agents’ use during CPB improved peripheral tissue perfusion while maintaining high flow during bypass. Hence, an improvement in perfusion and oxygenation of the skin, musculature and intestinal mucosa has been demonstrated, with favorable result throughout the postoperative period.These agents, by reducing systemic vascular resistance (SVR), lead to greater peripheral blood flow, improvement in peripheral perfusion, decreased base deficit and lactic acidosis and therefore improved respiratory and circulatory status.The present article reviews the main aspects of vasodilator agents most commonly used in pediatric cardiac surgery with CPB, including: chlorpromazine, phentolamine, phenoxybenzamine, sodium nitroprusside, volatile anesthetic agents, calcium channel blockers, angiotensin blockers and inodilators.

Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cbl-C type).

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.

Structural congenital heart disease in the newborn. Its differentiation from nonstructural cardiac or pulmonary disease.

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.

Congenital pulmonary atresia with tricuspid insufficiency: morphologic study.

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.