DEFECTIVE ENDOTHELIALLY MEDIATED PULMONARY VASODILATION IN SYSTEMIC-SCLEROSIS

Study objectives: Obliterative pulmonary vascular disease manifested c linically as pulmonary hypertension (PHT) may complicate systemic scle rosis (SSc). The aim of this study was to investigate possible endothe lial dysfunction in patients with SSC complicated by PHT. Design: Pros pective, randomized trial. Setting: Postgraduate teaching hospital. Pa tients: Patients having SSc with PHT (SSc-PHT) and SSc without PHT (SS c), confirmed using Doppler echocardiography, and normal individuals ( control subjects). Interventions: IV infusion of the endothelially dep endent vasodilator, substance P (maximum dose, 100 pmol/min), and the nonendothelially dependent vasodilator, adenosine (maximum dose, 0.05 mg/kg/min). Measurements and results: Effective pulmonary capillary bl ood flow (cardiac output minus right-to-left shunt) was measured in in ert gas rebreathing, and calculated stroke index (SI) was used to refl ect changes in pulmonary vascular resistance. During adenosine infusio n, patients with SSc-PHT (n = 5; mean age, 53 +/- 18 years) displayed a 25 +/- 16% increase in SI (p < 0.05 compared with baseline), but no significant changes in SI were detected in the SSc (n = 7; 54 +/- 6 ye ars) or control (n = 5; 35 +/- 5 years) groups. During infusion of sub stance P, SI rose by 32 +/- 18% in the control group at the maximum do se (p < 0.05), hut no change was observed in the SSc group. However, a fall in SI of -6 +/- 7% was detected in patients with SSc-PHT (p < 0. 05). Conclusions: Substance P-mediated pulmonary vasodilation is absen t in patients with systemic sclerosis, suggesting that endothelial dys function occurs early in the course of the illness, but some responsiv eness to adenosine remains.