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1 From the Department of Thoracic Medicine, Royal Brompton Hospital, London, UK
2 From the Pulmonary and Critical Care Division, Norwalk Hospital, Norwalk, Conn.
Study objectives: Obliterative pulmonary vascular disease manifested clinically as pulmonary hypertension (PHT) may complicate systemic sclerosis (SSc). The aim of this study was to investigate possible endothelial dysfunction in patients with SSC complicated by PHT.
Design: Prospective, randomized trial.
Setting: Postgraduate teaching hospital.
Patients: Patients having SSc with PHT (SSc-PHT) and SSc without PHT (SSc), confirmed using Doppler echocardiography, and normal individuals (control subjects).
Interventions: IV infusion of the endothelially dependent 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 blood flow (cardiac output minus right-to-left shunt) was measured in inert gas rebreathing, and calculated stroke index (SI) was used to reflect changes in pulmonary vascular resistance. During adenosine infusion, 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 years) or control (n=5; 35±5 years) groups. During infusion of substance P, SI rose by 32±18% in the control group at the maximum dose (p<0.05), but 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 absent in patients with systemic sclerosis, suggesting that endothelial dysfunction occurs early in the course of the illness, but some responsiveness to adenosine remains.
Key Words: pulmonary vasodilation • systemic sclerosis
Submitted on May 20, 1997
Accepted on December 15, 1997
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