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Updated: Aug 1, 2026

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Pulmonary Vascular Endothelial Dysfunction is Induced by Non-Pulsatile Pulmonary Blood Flow in an Ovine Classic Glenn
Jonathan Hyde1, Michael A Smith1, Naveen Swami2
1Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, USA.
Background:
Pulmonary vascular disease (PVD) in patients with single ventricular heart disease following the partial cavalpulmonary connection (Glenn) is a significant source of morbidity. However, the etiology of pulmonary vascular endothelial cell (EC) dysfunction, an established precursor to PVD, is incompletely understood but may involve abnormal blood flow patterns, hypoxemia, and polycythemia.
Hypothesis:
Utilizing an ovine Glenn model, we hypothesized that non-pulsatile pulmonary blood flow (PBF) induces pulmonary vascular EC dysfunction, independent of hypoxemia or polycythemia.
Methods:
Seven lambs (6-8 weeks old) underwent a Glenn procedure. Eight weeks later, Glenn and age-matched controls were studied. The response to the endothelium-dependent vasodilator acetylcholine (Ach) was determined in isolated pulmonary arteries (PA). Nitric oxide (NO) and endothelin-1 (ET-1) signaling was determined in right lung tissues. Indices of cell proliferation, angiogenesis, and apoptosis were determined in PA endothelial cells (PAECs). Comparisons were made by unpaired t-test and ANOVA.
Results:
There were no differences in age, hemoglobin, or oxygen saturation between groups. Mean PA pressure and left PA flow were higher, and right lung blood flow was lower in Glenn lambs compared to controls (p<0.05). All other baseline hemodynamics were similar. Glenn PAs had impaired relaxation to Ach. Glenn lung NO metabolite levels (NOx) and eNOS protein were lower, and ET-1 levels and prepro-ET-1 protein were higher than controls (p<0.05). Glenn PAECs had higher rates of proliferation and angiogenesis, and decreased apoptosis (p < 0.05).
Conclusions:
The initiation of non-pulsatile PBF following the Glenn induces early EC dysfunction independent of hypoxemia and polycythemia.
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