Persistent Pulmonary

Hypertension (PPHN)
F. Hazel R. Villa, MD
PL1
 Objectives
to review the fetal,transitional and postnatal
circulation in relation to PPHN

To understand the pathophysiology of PPHN

as it applies to clinical manifestations and
management
 Pulmonary vessels
VASOCONSTRICTORS VASODILATORS
(Maintain high fetal PVR) (Decrease PVR during
transition)
Norepinephrine
A-adrenergic stimulation PGI2, PGD2, PGE2
Hypoxia Nitric oxide
Endothelin Cyclic GMP
Thromboxanes Cyclic AMP
Leukotrienes Oxygen
Platelet activating factor Adenosine
PGF2a Bradykinin
Fetal circulation
 Fetal circulation

pO2, PGI2, NO
ADMA -- competes with arginine
inhibit NOS

Vasoconstriction
Postnatal circulation
Transitional circulation
 Transitional to postnatal

At birth
increase in NO, NOS- cGMP
increase guanylate cyclase- cGMP
increase in PGI2 (effect of estrogen) cAMP
DDAH metabolizes ADMA

Vasodilatation
 Transitional to postnatal

At birth
ventilation
increase pulmonary blood flow

Oxygenation
 Transitional to postnatal
Oxygen- stimulates NOS, COX1
Pulmonary blood flow- release of NO, PGI2

Evidence: NO-cGMP pathway is a more potent

modulator of pulmonary vascular tone
 Increase in SVR
Removal of the placenta

Catecholamine associated with birth

Cold environment
 Postnatal decrease in PVR
Expansion of the lung

Adequate ventilation, oxygenation

Clearance of fetal lung fluid

 3 types of abnormalities
Maladaptation

Maldevelopment

Underdevelopment
 Maladaptation
Prototype: Meconium aspiration pneumonia
Pneumonia, RDS

Obstruction of the airways

Chemical pneumonitis
Release of endothelin,thromboxane
vasoconstrictors
 Maldevelopment
Prototype: Idiopathic PPHN
(black lung PPHN)
Vessel wall thickening
Smooth muscle hyperplasia
Cause intrauterine exposure to NSAID
constriction of ductus arteriosus
genetic
 Maldevelopment
Disruption of NO-cGMP pathway
Disruption of PGI2-cAMP pathway
Guanylate cyclase is less active
Increased ROS (reactive oxygen species)
vasoconstrictor
Increased thromboxane, endothelin
 Underdevelopment
Prototype: Congenital diaphragmatic hernia
Pulmonary hypoplasia
Decreased cross sectional area of pulmonary
vasculature
Decreased pulmonary blood flow
Abnormal muscular hypertrophy of the pulm
arterioles
 Clinical signs and symptoms
PE:
meconium staining
Prominent precordial impulse
Narrow split accentuated P2
Systolic murmur LLSB
 Labs
CXR: CDH, decreased vascular markings,
parenchymal disease
ECG: RV predominance, ST elevation
ABG: hyperoxic test (pO2 < 100 at 100% O2)
Pre and postductal ABG (R radial artery:
umbilical artery/lower extremity)
10-15% saturation and or 10-15mmHg pO2
 Labs
Echocardiography
Structural heart disease is determined
R-L shunting (Ductus or FO)
Pulmonary arterial pressure is measured
 Management
Oxygen 100% pO2 should be kept between
50-90mmHg (O2 saturation >90%)
Correct factors promoting vasoconstriction:
hypoglycemia, hypocalcemia, anemia, hypovolemia

Optimize cardiac function (inotropic agents, volume

expansion

Mechanical ventilation
Surfactant
 Management
Inhaled Nitric oxide- an ideal selective
pulmonary vasodilator
OI of >25
OI=(MAP x FiO2)/pO2 x 100
Contraindications: CHD which are PDA dependent
(aortic stenosis, interrupted aortic arch, hypolastic heart
syndrome)
May worsen pulmonary edema in obstructed TAPVR

Used to transport patient for ECMO

 Management
ECMO
Goal of this treatment:
maintain adequate tissue oxygenation and
avoid irreversible lung injury, while PVR
decreases and correcting pulm HTN
ECMO if OI is >40
 Other Pulmonary Vasodilators
Sildenafil- PDE5 inhibitor increased cGMP
Milrinone- PDE3 inhibitor increased cAMP
Inhaled PGI2
Superoxide dismutase-superoxide scavenger
Dilates pulm vessels, and increase endogenous NO
 References
http://neoreviews.aappublications.org/cgi/content/full/8/1/e14
http://www.utdol.com/utd/content/topic.do?topicKey=neonatol
/1427&view=print
www.emedicine.com/ped/topic2530.htm
www.emedicine.com/PED/topic2530.htm
phassociation.org/medical/.../Summer_2006/persisten
t_ph_newborn.pdf
Thank you!