Bosentan and improved pulmonary endothelial function in pulmonary arterial hypertension: Figure 1–

Abstract

To the Editors: Pulmonary arterial hypertension (PAH) is characterised by pulmonary endothelial dysfunction and smooth muscle cell proliferation 1. Miniaturised catheter-based technology has recently enabled in vivo assessment of both endothelial dysfunction and pulmonary artery thickening in vivo 2, 3. Bosentan, an oral dual endothelin-1 receptor antagonist, has been shown to improve clinical outcomes in PAH 4. In vitro , bosentan has been shown to improve human endothelial cell function 5 and reduce neointimal and smooth muscle proliferation. In pigs in vivo , bosentan has been shown to partially restore hypoxia-induced reductions in nitric oxide 6. The effect of bosentan on human pulmonary artery structure and function in vivo , however, has not been studied. We hypothesised that bosentan therapy might improve pulmonary microvascular endothelial function and pulmonary artery remodelling in patients with established PAH. Therefore, we assessed the effect of 6 months of clinically indicated bosentan therapy in patients with advanced PAH on: 1) pulmonary microvascular function, assessed by Doppler-derived pulmonary blood flow responses to vasoactive agents; and 2) segmental pulmonary artery structure, measured by pulmonary intravascular ultrasound (IVUS). Eight bosentan-naive subjects (three males and five females; five subjects with idiopathic and three with scleroderma-related PAH; mean±sem age 66±4 yrs; weight 79±5 kg) were studied. The institutional review board (Royal Prince Alfred Hospital, Sydney, NSW, Australia) approved the study protocol and informed consent was obtained from all subjects. All patients were in New York Heart Association (NYHA) functional class III, had mean pulmonary arterial pressure ( P pa) >25 mmHg at rest (without demonstrable reversibility) and had pulmonary capillary wedge pressure ≤15 mmHg. Clinically indicated right heart catheterisation, assessing suitability for bosentan prescription, was performed. Thereafter, pulmonary artery IVUS assessment was performed in a distal segmental pulmonary artery of both upper and lower lobes …