HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Eugene V. Vitvitsky Thomas L. Spray J. William Gaynor Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vitvitsky, E. V. Articles by Gaynor, J. W. Search for Related Content PubMed PubMed Citation Articles by Vitvitsky, E. V. Articles by Gaynor, J. W.

Ann Thorac Surg 1998;66:1372-1377
© 1998 The Society of Thoracic Surgeons

---

Original articles: cardiovascular

Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine

^a Pediatric Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
^b Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Address reprint requests to Dr Gaynor, Pediatric Cardiothoracic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104
e-mail: (gaynor{at}email.chop.edu)

Presented at the Poster Session of the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

Background. The mechanisms by which increased pulmonary blood flow results in pulmonary hypertension have not been determined.

Methods. To determine if increased pulmonary blood flow produces endothelial dysfunction that precedes vascular remodeling and smooth muscle proliferation, neonatal swine (n = 12) (age, 6.1 ± 0.5 days) underwent ligation of the left pulmonary artery (LPA) to increase blood flow to the right lung. At 12 weeks of age, endothelium-dependent vasodilatation was assessed by acetylcholine infusion and endothelium-independent vasodilatation by inhaled nitric oxide (NO) in the LPA group and age-matched controls (CON) (n = 11).

Results. Mean pulmonary artery pressure was 24.1 ± 3.0 mm Hg in the LPA group and 20.8 ± 1.9 mm Hg in the CON group (p < 0.1). Pulmonary vascular resistance was 13.2 ± 2.2 Wood units in the LPA group and 5.8 ± 0.8 Wood units in the CON group (p = 0.001). Acute occlusion of the left pulmonary artery in the CON group increased pulmonary vascular resistance to 6.9 ± 3.9 Wood units (p = 0.04). Administration of acetylcholine in the CON group after preconstriction with the thromboxane A₂ analogue U46619 resulted in a 30.6% ± 5.4% decrease in pulmonary vascular resistance. In the LPA group, acetylcholine produced paradoxical vasoconstriction and a 15.4% ± 4.1% increase in pulmonary vascular resistance (p < 0.001 versus CON) indicating loss of endothelium-dependent vasodilatation. Nitric oxide decreased pulmonary vascular resistance by 41.9% ± 3.3% in the CON group and 30.8% ± 2.7% in the LPA group (p = 0.04 versus CON), indicating preserved endothelium-independent vasodilatation in both groups. Morphometric analysis was performed in 4 animals from each group. Medial wall thickness as percent of external diameter of small arteries (<100 µm) was the same in both groups (6.4% ± 0.4% in the LPA group versus 6.6% ± 0.4% in the CON animals; p > 0.1).

Conclusions. Increased pulmonary blood flow in immature animals produces endothelial cell dysfunction with loss of endothelium-dependent vasodilatation before the onset of pulmonary vascular remodeling. Subsequent smooth muscle proliferation may be mediated by endothelium-derived factors.

This article has been cited by other articles:

				T.-F. Chou, M.-S. Wu, C.-T. Chien, C.-C. Yu, and C.-F. Chen Enhanced expression of nitric oxide synthase in the early stage after increased pulmonary blood flow in rats Eur. J. Cardiothorac. Surg., February 1, 2002; 21(2): 331 - 336. [Abstract] [Full Text] [PDF]

				M. Medhora, M. Bousamra II, D. Zhu, L. Somberg, and E. R. Jacobs Upregulation of collagens detected by gene array in a model of flow-induced pulmonary vascular remodeling Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H414 - H422. [Abstract] [Full Text] [PDF]