To the Editor:—
We read with interest the comprehensive series presented by Bonnin et al. 1Their report of the treatment of severe pulmonary hypertension (PHTN) during pregnancy in their institution from 1992 to 2002 is a timely reminder of the high maternal and fetal mortality from this condition. We would like to draw the readers’ attention to the emerging role of phosphodiesterase inhibitors (PDEs), such as sildenafil, in the treatment of PHTN. Clinical trials have demonstrated that oral sildenafil is effective in the treatment of both acute and chronic PHTN2–4of a variety of etiologies.5,6In addition, several recent reports exist of its successful use in pregnant patients with this devastating disease process.7,8
Phosphodiesterase inhibition has been demonstrated to treat PHTN by reducing cyclic guanosine monophosphate breakdown, making pulmonary vascular smooth muscle more sensitive to endogenous and administered nitric oxide.9This reduces ventilation perfusion mismatch and hypoxia.3,10Of the PDE5 inhibitors studied, sildenafil has the greatest selectivity for the pulmonary circulation and arterial oxygenation.11The use of PDE inhibitors seems safe in both ischemic heart disease12and heart failure.13The effect of PDEs on pulmonary vasculature and pulmonary artery pressure has been studied in comparison to and in combination with inhaled iloprost and inhaled nitric oxide,14–16and it augments their vasodilatory effects.17,18In fact, sildenafil is at least as effective as inhaled nitric oxide in relaxing the pulmonary vasculature and may have fewer side effects.19Coadministration of sildenafil with nitric oxide also leads to less rebound PHTN, a major problem with nitric oxide administration, caused by down-regulation of nitric oxide synthetase.15
Sildenafil has other potentially beneficial effects in this context. It causes uterine artery vasodilation and has been shown to improve uterine muscle wall thickness in in vitro fertilization patients with previous poor endometrial response.20In addition, sildenafil and nitric oxide are being used successfully to treat preterm and term neonatal and childhood PHTN.21,22
The therapeutic potential of sildenafil in the treatment of PHTN during pregnancy awaits definitive demonstration in the form of a clinical trial. However, its proven effectiveness and safety in other forms of pulmonary hypertension, coupled with ease of oral administration and its apparent lack of teratogenicity, mean that it is a highly promising therapy for severe pulmonary hypertension in pregnant patients.
*University College Hospital Galway, Galway, Ireland. firstname.lastname@example.org