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

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Pulmonary Veins: Development and Physiology

• J. USHA RAJ, MD

ANJULI S. NAYAK PROFESSOR OF PEDIATRICS UNIVERSITY OF ILLINOIS AT CHICAGO

I have no financial interest or other relationship with any manufacturer/s

• f any commercial product/s which

may be discussed at this activity.

Disclosure Statement

Development of Lung Arteries and Veins: Serial reconstruction in a 34-day human embryo

Hislop AA, J Anat 2002

Ephrin B2 specific for arteries: Ephrin B4 for veins

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Endothelial Ephrin B2 and B4 regulate guided migration and control arterio-venous positioning

Fuller T, et al J Cell Sc 2003

Presence of Arteries and Veins in 6 wk human embryo

Development of Airways and Vessels in 17 wk human embryo

Bronchial Smooth Muscle migrates into arterial vessel wall

Bronchial SMC do NOT migrate into

• veins. Fibroblasts

migrate into Veins.

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Large Rat Intrapulmonary Veins have Cardiac Smooth Muscle

Townsley M., Comp Physiol 2013

Comparison of Smooth Muscle Coat Thickness in Arteries and Veins Arterial, Microvascular and Venous Resistances in the Lung Veins Impose Significant Resistance in the Developing Lung

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Effect of Blood Flow on Pulmonary Artery Pressure when Venous Resistance is High

Both Arteries and Veins Constrict During Hypoxia in Newborn Lambs Increased Fluid Filtration During Hypoxia in Newborn Lambs

Bressack and Bland, Circ Res 1980

Fluid Filtration is Unchanged in Hypoxia in Adult Sheep

Bland et al, Circ Res 1977

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Vasoactive Mediators acting on Arteries and Veins

Smooth muscle cell Endothelial Cells

RELAXATION cGMP cAMP

Arachidonic Acid

eNOS

MEMBRANE PHOSPHOLIPIDS Nitric Oxide PGI2, PGE2

Pre Pro - ET ET1

ET-B ET-A

CONTRACTION

Thromboxane PAF

Greater contraction to Endothelin in Pulmonary Veins Compared to Arteries in Piglets Decreases with Age

Schindler et al, Am J Physiol, 2007

Veins Have Strong Relaxation Responses

Gao et al, Circ Res, 1995

Is there Venous Remodeling In the Lung?

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Arterial Remodeling in PPHN

Chronic Hypoxia in Fetal Lambs induces Arterial remodeling Only

Female lambs % wall thickness

5 10 15 20 25 30 35 40 Bronchiolus TB RB AD Vein % wall thickness Normoxia Hypoxia

Hypoxia-Induced Pulmonary Venous Remodeling in Piglets

Schindler et al, Am J Physiol, 2007

Pulmonary Venous Remodeling in Adults with Atrial Fibrillation and Cardiac Disease

Yoshida K, et al, Am J Cardio 2017

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Narrowing of Venous Lumen due to Discrete Thickening of Muscle Coat in Preterm babies

Pogoriler et al, Ped Dev Path, 2016

Vascular Pathology in Pulmonary Vein Stenosis

Pogoriler et al, Ped 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.