Document Detail


Impact of mechanical unloading on microvasculature and associated central remodeling features of the failing human heart.
MedLine Citation:
PMID:  20650360     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart.
BACKGROUND: Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among microvasculature, fibrosis, and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown, and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial.
METHODS: Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n = 15) and from normal donors (n = 8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size, and glycogen content. Ultrastructural assessment was done with electron microscopy.
RESULTS: Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p = 0.001) and a 36% decrease in microvascular lumen area (p = 0.028). We also identified, in agreement with these findings, ultrastructural and immunohistochemical evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural, or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration.
CONCLUSIONS: The LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features might guide future studies of unloading-induced reverse remodeling of the failing human heart.
Authors:
Stavros G Drakos; Abdallah G Kfoury; Elizabeth H Hammond; Bruce B Reid; Monica P Revelo; Brad Y Rasmusson; Kevin J Whitehead; Mohamed E Salama; Craig H Selzman; Josef Stehlik; Stephen E Clayson; Michael R Bristow; Dale G Renlund; Dean Y Li
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  56     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-09     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  382-91     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Cardiovascular Department and Utah Artificial Heart Program, Intermountain Medical Center, Salt Lake City, Utah, USA. stavros.drakos@u2m2.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cardiology / methods
Cardiomegaly / pathology
Endothelium / pathology
Female
Heart Failure / therapy*
Heart Ventricles / pathology
Heart-Assist Devices*
Humans
Hypertrophy
Male
Microcirculation*
Microscopy, Electron / methods
Middle Aged
Myocardium / pathology
Stress, Mechanical
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
C06-RR11234/RR/NCRR NIH HHS; R01 HL068873-08/HL/NHLBI NIH HHS; R01 HL077671-06/HL/NHLBI NIH HHS; R01 HL077671-07/HL/NHLBI NIH HHS; R01 HL084516-04/HL/NHLBI NIH HHS; R01 HL089592-03/HL/NHLBI NIH HHS; UL1-RR025764/RR/NCRR NIH HHS
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