Role of pharmacologic tests in the treatment of primary pulmonary hypertension

Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology characterized by a constant progression toward right ventricular failure and death. Vasoconstriction is 1 of the pathophysiologic factors responsible for the increase of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) in patients with PPH. Thus vasodilator treatment is considered 1 of the logical approaches to medical therapy of such a condition. Acute drug challenge with a short-acting, titratable vasodilator during heart catheterization is recommended to select patients who are most likely to respond to long-term treatment. Accurate methodologic guidelines need to be followed to minimize the spontaneous variability of PAP and pulmonary arteriolar resistance. Pathophysiologic interpretation of pharmacologic trials requires analysis of the 2 components of the right ventricular hydraulic load, i.e., resistance and compliance of the pulmonary vascular bed. Reduction of the calculated PVR may be considered as a demonstration of pulmonary vasodilation only if PVR is assessed using the critical opening pressure or if it is associated with a simultaneous reduction of PAP. Only those patients in whom a reduction of PVR of > or = 20% is associated with a decrease in PAP of > or = 20% should be considered as "responders" to the acute tests. In clinical studies only 20-30% of the patients are short-term responders. The most intensively studied short-acting drug for short-term challenge is prostacyclin, but other agents such as acetylcholine, adenosine, and nitric oxide have been utilized. Prostacyclin has been shown to predict pulmonary vasodilator response to the administration of long-acting vasodilators, such as calcium channel antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)