Pulmonary Vascular Endothelial Dysfunction Is Induced by Nonpulsatile Pulmonary Blood Flow in an Ovine Classic Glenn...

Area of Science:

• Cardiovascular Research
• Pediatric Cardiology
• Vascular Biology

Background:

• Pulmonary vascular disease (PVD) is a major complication in single ventricle heart disease (SVHD) patients post-Glenn procedure.
• Endothelial cell (EC) dysfunction is an early step in PVD development, but its causes in this context are unclear.
• Potential factors include altered hemodynamics, hypoxemia, and polycythemia.

Purpose of the Study:

• To investigate if nonpulsatile pulmonary blood flow (PBF) causes EC dysfunction in an ovine Glenn model.
• To determine if this dysfunction is independent of hypoxemia or polycythemia.

Main Methods:

• Seven lambs underwent a Glenn procedure, with studies conducted 8 weeks later.
• Pulmonary artery responses to acetylcholine (Ach) were assessed.
• Nitric oxide (NO) and endothelin-1 (ET-1) signaling, EC proliferation, angiogenesis, and apoptosis were analyzed in lung tissue and pulmonary artery endothelial cells (PAECs).

Main Results:

• Glenn lambs showed impaired vasodilation to Ach and altered NO/ET-1 signaling.
• Increased PA pressure and altered lung blood flow distribution were observed in Glenn lambs.
• PAECs from Glenn lambs exhibited increased proliferation and angiogenesis, with decreased apoptosis.

Conclusions:

• Nonpulsatile PBF post-Glenn procedure initiates early pulmonary vascular EC dysfunction.
• This dysfunction occurs independently of hypoxemia and polycythemia.
• Findings suggest nonpulsatile flow is a key factor in developing PVD after the Glenn procedure.