Defective endothelially mediated pulmonary vasodilation in systemic sclerosis

Area of Science:

• Cardiovascular Medicine
• Rheumatology
• Pulmonary Medicine

Background:

• Systemic sclerosis (SSc) can lead to obliterative pulmonary vascular disease, clinically presenting as pulmonary hypertension (PHT).
• Endothelial dysfunction is a suspected contributor to the development of PHT in SSc.

Purpose of the Study:

• To investigate endothelial dysfunction in patients with SSc complicated by PHT.
• To assess the pulmonary vascular response to an endothelium-dependent vasodilator (substance P) and an independent vasodilator (adenosine) in SSc patients with and without PHT.

Main Methods:

• Prospective, randomized trial conducted at a postgraduate teaching hospital.
• Participants included patients with SSc and PHT (SSc-PHT), SSc without PHT (SSc), and healthy controls.
• Intravenous infusions of substance P and adenosine were administered to assess pulmonary vascular resistance changes via stroke index (SI).

Main Results:

• Patients with SSc-PHT showed a significant increase in SI during adenosine infusion, unlike SSc or control groups.
• Control subjects exhibited increased SI with substance P, while SSc patients showed no change.
• SSc-PHT patients demonstrated a significant fall in SI during substance P infusion, indicating impaired vasodilation.

Conclusions:

• The absence of substance P-mediated pulmonary vasodilation in SSc patients suggests early endothelial dysfunction.
• Some degree of pulmonary vascular responsiveness to adenosine persists in SSc-PHT.
• These findings highlight potential early endothelial alterations in SSc-related pulmonary hypertension.