Vasodilators in the treatment of primary pulmonary hypertension.

Abstract

be identified? There is nothing in the duration of their symptoms, clinical presentation or baseline haemodynamics to indicate which patients will respond. In a paper in this issue of the European Respiratory Journal, SITBON et al. [14] report a comparison of the acute haemodynamic responses to inhaled nitric oxide and to high-dose oral CCB (nifedipine or diltiazem) in 33 consecutive PPH patients. Of these patients, ten showed a fall in both mean pulmonary artery pressure and total pulmonary resistance of >20% after inhaled nitric oxide. Nine of the 10 patients also responded acutely to CCB. The other 23 patients failed to respond to either nitric oxide or CCB. Consequently in this series, there were no patients who responded to CCB who did not also respond to nitric oxide. If this is confirmed in a larger series, nitric oxide will be the agent of choice to determine which patients would be candidates for long-term CCB treatment. The administration of nitric oxide (10 parts per million (ppm)) is fast and relatively inexpensive compared to prostacyclin. The same group has reported that the acute responses of pulmonary artery pressure and resistance to nitric oxide and prostacyclin are closely correlated [15]. In that study of 35 PPH patients, 13 patients (37%) had a fall in total pulmonary resistance >30% in response to both drugs, while 22 were nonresponders to both. Although occasional patients who respond to prostacyclin may fail to respond to nitric oxide, the key conclusion from the present paper [14] is that nitric oxide testing identifies most, or possibly all, of those who might benefit from long-term oral CCB. If nitric oxide can be relied upon to do this, then an acute trial with high-dose oral CCB, which carries the greatest risk of side-effects in nonresponders, will not be necessary. It is interesting that 38% of the nonresponders suffered serious side-effects from the acute trial of CCB (shock, prolonged hypotension or severe vomiting), compared to 6% in an earlier study [10]. It is possible that the preceding trial of nitric oxide initiated some longer-lasting changes in vascular smooth muscle physiology, which rendered the patients more susceptible to CCB-induced hypotension. The problem with CCB is that they are not selective for the voltage-gated, L-type calcium channels in pulmonary vascular smooth muscle and consequently can precipitate systemic hypotension. Potassium channels are largely responsible for the control of vascular smooth muscle membrane potential and thus can determine the gating of the L-type calcium channel. Given the greater number of potassium channels and the diversity of their expression in different blood vessels [16, 17], it may be possible to develop potassium channel agonists that cause only pulmonary vasodilatation. Other new approaches to the treatment of PPH include nebulizing prostacyclin or its stable analogue iloprost [18]. This mode of delivery may be more convenient, induce