Document Detail


Persistent vascular collagen accumulation alters hemodynamic recovery from chronic hypoxia.
MedLine Citation:
PMID:  22183202     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z(0)), characteristic impedance (Z(C)), pulse wave velocity (PWV) and index of global wave reflections (P(b)/P(f)), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1(R/R)) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1(+/+)) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z(0) (mPAP/CO) increased by ~100% in both genotypes (p<0.05). Contrary to our expectations, Z(C), PWV and P(b)/P(f) did not change. However, with recovery, Z(C) and PWV decreased in the Col1a1(+/+) mice and remained unchanged in the Col1a1(R/R) mice. Z(0) decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function.
Authors:
Diana M Tabima; Alejandro Roldan-Alzate; Zhijie Wang; Timothy A Hacker; Robert C Molthen; Naomi C Chesler
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-17
Journal Detail:
Title:  Journal of biomechanics     Volume:  45     ISSN:  1873-2380     ISO Abbreviation:  J Biomech     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-05     Completed Date:  2012-09-11     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0157375     Medline TA:  J Biomech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  799-804     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biomedical Engineering, University of Wisconsin-Madison, WI 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / metabolism*,  pathology
Blood Flow Velocity / physiology
Cardiac Output / physiology
Collagen Type I / metabolism*
Female
Hemodynamics
Hypertension, Pulmonary / metabolism*,  pathology
Lung / blood supply,  metabolism,  pathology
Male
Mice
Pulmonary Artery / metabolism,  pathology
Pulmonary Circulation / physiology
Vascular Resistance
Ventricular Function, Right / physiology
Grant Support
ID/Acronym/Agency:
R01 HL086939/HL/NHLBI NIH HHS; R01 HL086939-03/HL/NHLBI NIH HHS; R01 HL086939-04/HL/NHLBI NIH HHS; R01 HL086939-05/HL/NHLBI NIH HHS; R01HL086939/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Collagen Type I
Comments/Corrections

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