The Effects of Vasodilators in Pulmonary Hypertension
Pulmonary Vascular or Peripheral Vascular?
When primary pulmonary hypertension (PPH) was first described in the medical literature, it was characterized from a cardiac catheterization on a young woman who had an elevated pulmonary arterial pressure of unknown origin which, after the intravenous administration of acetylcholine, promptly fell.1 The sentinel description of this phenomenon led to the acceptance of PPH as a medical entity in which inappropriate pulmonary vasoconstriction was a central feature.2 Since then many series of patients with PPH (now referred to as idiopathic pulmonary arterial hypertension [IPAH]) have been published which document a variable ability to respond to acute vasodilator challenge. Although, the approach to therapy has emphasized the initial classification of responder or nonresponder, most patients demonstrate only a small decrease in pulmonary pressure (PAP) in response to vasodilators.3 However, vasodilators are widely prescribed in patients who are nonresponders, based on clinical trials that established the response to a 6-minute walk (6 MW) test as the primary end point.4 The consistent improvement in 6 MW reflects the complexity of exercise intolerance, which may be strongly influenced not only by cardiopulmonary factors, but by peripheral factors such as the muscle ergoreflex.5
Who is a Responder?
In the current era, patients with PAH6 who undergo acute vasoreactivity testing at the time of diagnosis are classified as responders or nonresponders based on the change in PAP from select agents.7 The definition of a responder has changed many times, the most recent being a fall in the mean PAP of at least 10 mmHg to a level below 40 mmHg without any fall in cardiac output.4 However, the response is in reality a continuum, and not an all or none phenomenon. It is notable that in 2 large series of patients who were deemed acute responders, the characteristic of those who had …