Pulmonary Veins: Development and I have no financial interest or - PowerPoint PPT Presentation

3/10/2017 Disclosure Statement Pulmonary Veins: Development and I have no financial interest or other relationship with any manufacturer/s Physiology of any commercial product/s which may be discussed at this activity . J. USHA RAJ, MD ANJULI S. NAYAK PROFESSOR OF PEDIATRICS UNIVERSITY OF ILLINOIS AT CHICAGO Development of Lung Arteries and Veins: Serial reconstruction in a 34-day human embryo Ephrin B2 specific for arteries: Ephrin B4 for veins Hislop AA, J Anat 2002 1

3/10/2017 Endothelial Ephrin B2 and B4 regulate guided Presence of Arteries and Veins in 6 wk migration and control arterio-venous positioning human embryo Fuller T, et al J Cell Sc 2003 Development of Airways and Vessels in 17 wk Bronchial Smooth Muscle migrates into human embryo arterial vessel wall Bronchial SMC do NOT migrate into veins. Fibroblasts migrate into Veins. 2

3/10/2017 Large Rat Intrapulmonary Veins have Cardiac Comparison of Smooth Muscle Coat Smooth Muscle Thickness in Arteries and Veins Townsley M., Comp Physiol 2013 Veins Impose Significant Resistance in the Arterial, Microvascular and Venous Developing Lung Resistances in the Lung 3

3/10/2017 Both Arteries and Veins Constrict During Effect of Blood Flow on Pulmonary Artery Hypoxia in Newborn Lambs Pressure when Venous Resistance is High Increased Fluid Filtration During Hypoxia in Fluid Filtration is Unchanged in Hypoxia in Newborn Lambs Adult Sheep Bressack and Bland et al, Bland, Circ Circ Res 1977 Res 1980 4

3/10/2017 Greater contraction to Endothelin in Pulmonary Veins Compared to Vasoactive Mediators acting on Arteries and Veins Arteries in Piglets Decreases with Age Endothelial Cells eNOS MEMBRANE PHOSPHOLIPIDS Schindler et al, Am J Pre Pro - ET ET1 Physiol, 2007 Thromboxane Arachidonic Acid ET-B ET-A PAF CONTRACTION Nitric Oxide PGI 2 , PGE 2 Smooth muscle cell RELAXATION cGMP cAMP Veins Have Strong Relaxation Responses Is there Venous Remodeling In the Lung? Gao et al, Circ Res, 1995 5

3/10/2017 Arterial Remodeling in PPHN Chronic Hypoxia in Fetal Lambs induces Arterial remodeling Only Female lambs % wall thickness 40 35 30 % wall thickness 25 Normoxia 20 Hypoxia 15 10 5 0 Bronchiolus TB RB AD Vein Hypoxia-Induced Pulmonary Venous Remodeling in Piglets Pulmonary Venous Remodeling in Adults with Atrial Fibrillation and Cardiac Disease Schindler et al, Am J Yoshida K, Physiol, 2007 et al, Am J Cardio 2017 6

3/10/2017 Vascular Pathology in Pulmonary Vein Stenosis Narrowing of Venous Lumen due to Discrete Thickening of Muscle Coat in Preterm babies Pogoriler et al, Ped Pogoriler et al, Ped Dev Path, 2016 Dev Path, 2016 58% of PV stenosis had vessel wall thickening Both Pulmonary Arterial and Venous Pathology plays a Role in Pulmonary Hypertension • Venous disease is increasingly being recognized as an important entity in PH • Pulmonary Veins when remodeled are “arterialized” making identification of venous pathology difficult • Necessary to have a high index of suspicion for presence of Pulmonary Venous Pathology. 7