Pulmonary Hypertension

Question 1

What are the three basic mechanisms that cause pulmonary hypertension?

Answer 1

1. Increased pulmonary blood flow (increased CO, left to right shunt)
2. Increased precapillary resistance (constriction, obliteration, obstruction)
3. Abnormal or increased postcapillary resistance (pulmonary vein obstruction, left atrial obstruction, mitral or aortic valve disease, LV dysfunction)

Question 2

What is Eisenmenger syndrome?

Answer 2

Triad of systemic-to-pulmonary congenital cardiac disease (left to right shunt), pulmonary arterial disease and cyanosis

Initially left to right shunt, resulting in increased pulmonary blood flow, remodeling, increased PVR and ultimately reversal of shunt flow

Question 3

True or False:

Pulmonary vasculature is designed for maximal compliance

Answer 3

True!
Pulmonary vasculature is designed for maximal compliance. It can accommodate the full cardiac output at 20% of the systemic pressure. The normal pulmonary circulation can accept 2.5x the usual cardiac output without an increase in PAP.

Plus, there is reserve vasculature that can be recruited when needed to further accommodate increased pulmonary blood flow.

Question 4

Principals of management of pulmonary hypertension:

First, do no harm. What are triggers of pulmonary hypertension that should be avoided?

Answer 4

Hypoxia (global hypoxia causes pulmonary vasoconstriction and systemic vasodilation -> results in increased pulmonary vascular resistance and decreased coronary perfusion pressure through decreased aortic diastolic pressure)
Acidosis
Elevated intra-thoracic pressure
Increased blood concentrations of vasoconstrictors or procoagulants

Question 5

What is milrinone and how does it work?

Answer 5

A phosphodiesterase III inhibitor
Decreases the breakdown of cAMP
Increases the concentration of intracellular calcium

Increases cardiac contractility
Decreases SVR
May decrease PVR

Question 6

What is nitric oxide and how does it work?

Answer 6

Produced by endothelial cells.
Acts via a cGMP mechanism to inhibit platelet aggregation, dilate vessels and inhibit vascular proliferation

When delivered by inhaled form, it vasodilates pulmonary vessels, is absorbed and inactivated by hemoglobin, resulting in little effect on the systemic vasculature

Question 7

The main pharmacologic mechanisms for pulmonary vasodilation are cAMP, cGMP, calcium channel blockade. Name a drug for each mechanism.

Answer 7

cAMP: Milrinone (PDE3 inhibitor), prostacyclin (esoprostenol)
cGMP: nitric oxide, sildenafil (PDE5 inhibitor)
Calcium channel blockade