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PMID: 9327735 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Pulmonary hemodynamics modify the rat pulmonary artery response to injury. A neointimal model of pulmonary hypertension.

The American journal of pathology ·Vol. 151 ·No. 4 ·1997-10-00 ·Pages 1019-25

Okada K, Tanaka Y, Bernstein M, Zhang W, Patterson GA, Botney MD

Abstract

Hemodynamic factors have profound influences on blood vessels. To test the hypothesis that hemodynamic conditions modify the pattern of remodeling in response to injury, monocrotaline (MCT) injury in Sprague-Dawley rats was followed 1 week later by left pneumonectomy to increase blood flow to the right lung. Right pulmonary artery remodeling in these MCT plus pneumonectomy animals was compared with animals receiving MCT or pneumonectomy alone. Neointimal changes developed in more than 90% of all right lung intra-acinar vessels 5 weeks after MCT injury (4 weeks after pneumonectomy). Neointimal lesions did not develop in untreated animals or in animals receiving MCT or pneumonectomy only. Animals with a neointimal pattern of remodeling developed severe right ventricular hypertrophy (RVH) whereas animals with a medial hypertrophy pattern of remodeling (MCT only) developed moderate RVH compared with control animals. Neointimal lesions and RVH were similar whether injury preceded pneumonectomy or vice versa. To exclude the possibility that neointimal lesions resulted from injury plus post-pneumonectomy compensatory lung growth, rather than injury plus increased flow, a left subclavian-pulmonary artery anastomosis was substituted for pneumonectomy. Neointimal lesions and severe RVH developed in these animals but were not seen in animals receiving either MCT or anastomosis only. These studies demonstrate an important role for hemodynamics in determining the pattern of pulmonary vascular remodeling after injury.

MeSH Terms
Actins/metabolism Animals Disease Models, Animal Hemodynamics/physiology Hyperplasia Hypertension, Pulmonary/chemically induced,pathology,physiopathology Hypertrophy, Right Ventricular/pathology Immunohistochemistry Lung/blood supply,pathology,surgery Male Monocrotaline Pneumonectomy Pulmonary Artery/pathology,physiopathology Pulmonary Circulation/physiology Rats Rats, Sprague-Dawley Specific Pathogen-Free Organisms Tunica Intima/metabolism,pathology,physiopathology
Chemicals
Actins Monocrotaline
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Okada K
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Tanaka Y
Bernstein M
Zhang W
Patterson G A
Botney M D
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1997-10-00
Pages
1019-25
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1858047
Subset
IM
Grants
NHLBI NIH HHS · HL29594 · United States
NHLBI NIH HHS · HL41281 · United States
External Links
PubMed source PMC Full Text View journal details
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