Vasodilators in the treatment of primary pulmonary hypertension.

The use of vasodilators to reduce vascular resistance is over a hundred years old. BALFOUR [1] recommends the use of nitrites as vascular stimulants "which dilate the peripheral vessels (arterioles) and so promote the flow blood". In the case of primary pulmonary hypertension (PPH), vaso-constriction is one of three factors that combine to increase resistance to blood flow through the lungs. The other two being thrombosis in situ and intimal proliferation of the small pulmonary arteries. In the absence of contra-indications, anticoagulation is appropriate in PPH patients [2, 3]. Although intimal proliferation is probably the most important element in PPH, our ignorance of the pathophysiology has, to this point, prevented the development of an effective treatment directed against cellular proliferation. Any success that there has been in this regard has been secondary to the use of agents thought primarily to be vasodilators. Vasodilators have been tried in the management of PPH since the use of tolazoline in 1951 [4]. The recent resurgence of interest started with reports of the efficacy of dia-different vasodilators were reported to have been used acutely to try to determine how much vasoconstriction contributed to the pulmonary hyperten-sion [7]. Fortunately, the number of agents administered acutely as a trial of responsiveness has diminished considerably. In most centres the choice now is between adeno-sine (i.v.), prostacyclin (i.v.), calcium channel blockers (CCB; p.o.), and inhaled nitric oxide. At present, long-term "vasodilator" treatment options are CCB (p.o.) or constant infusion of prostacyclin (i.v.). Experience with CCB dates back to 1983 [8]. Subsequent work by RICH and coworkers [9, 10] indicates that rather less than one-third of PPH patients will have an acute response to CCB (>20% reduction in pulmonary artery pressure and resistance). The majority of these responders will maintain the haemodynamic improvement during long-term follow-up. Those who do not respond acutely are best treated with prostacyclin or lung transplantation. Pro-stacyclin treatment carries the risk of septicaemia and accidental interruption of infusion, but has been remarkably effective, even in patients who showed no initial, acute vasodilator response [11–13]. It seems likely that prosta-cyclin is having effects in addition to vasodilatation, possibly through inhibition of cellular proliferation or of platelet activation. Given the relative ease of treating those patients who respond acutely to vasodilators with CCB, how can they be identified? There is nothing in the duration of their symptoms, clinical presentation or baseline haemodyna-mics to indicate which patients will …