Effect of Dynamic Hyperinflation on Pulmonary Hemodynamics and Right Ventricular function in Chronic Obstructive Pulmonary Disease

Lung hyperinflation is defined as increased air volume at the end of a normal,
spontaneous expiration, called the End-Expiratory Lung Volume (EELV), and
develops in COPD because of a decrease in lung compliance due to irreversible
destructive changes of emphysema.
During exercise the rate and depth of inspiration normally increase. In COPD,
airflow limitation due to the airway obstruction together with lowered
expiration time during exercise will lead to an insufficient emptying of the
lung at expiration, resulting in a progressive increase of EELV This *dynamic*
hyperinflation (DH), which is dependent of expiratory airflow and expiratory
time [1] leads to a disproportional increase in the work of breathing and
dyspnoea sensation. [2] Recently it was found that dynamic hyperinflation is
present even during daily activities in COPD patients.[3] A direct consequence
of dynamic hyperinflation is increased intrathoracic pressure at end of
expiration. Although the effects of increased intrathoracic pressure on
pulmonary hemodynamics are well studied in healthy subjects in the so called
Valsalva manoeuvre, where they lead to an increase in pulmonary artery pressure
and a drop in cardiac output. However, the effects on right ventricular
function are unknown and in addition to that, the situation in dynamic
hyperinflation is different from the Valsalva manoeuvre since increased
expiratory pressures are followed within seconds by a decreased pressure at
inspiration. The effects of these pressure swings between in- and expiration on
the hemodynamics and right ventricular function are unknown. Our central
hypothesis is that dynamic hyperinflation induces an afterload increase for the
right ventricle and impairs stroke volume augmentation in exercise.

Questions/aims
To study the effects of dynamic hyperinflation on pulmonary hemodynamics and
right and left ventricular function we formulated the following questions.

Do COPD patients with dynamic hyperinflation have a more impaired response of
stroke volume and cardiac output at exercise than COPD patients with a similar
GOLD classification without dynamic hyperinflation?

What is the effect of dynamic hyperinflation on right and left ventricular
function in COPD?

What is the effect of dynamic hyperinflation on systemic oxygen delivery and
extraction?

Does the reduction of dynamic hyperinflation in COPD by Heliox (Helium-Oxygen)
inhalation lead to afterload reduction of the right ventricle and by that to
improvement of the cardiac output augmentation during exercise?

What is the influence of dynamic hyperinflation and stroke volume impairment on
the outcomes of the rehabilitation program.

Observational study.


RHC at rest, maximal exercise test and a submaximal exercise while breathing
Heliox
cardiac MRI at rest and during submaximal exercise.

Patients will be hospitalized for 2 days. The main burden for the patients will
be the RHC together with an esophageal balloon and arterial canula. Apart from
that, there is one moment of blood sampling. During the 2 days, patients have
to perform 1 maximal exercise test and 2 submaximal exercise test.
The risks are the same as the known risks for RHC and arterial cannulation.