Document Detail

Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat.
MedLine Citation:
PMID:  23001837     Owner:  NLM     Status:  Publisher    
The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodelling. Corresponding changes in 3D organization of cardiac extracellular matrix (ECM) have not previously been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls were studied at 3, 12, 18 and 24 months. Hemodynamic and morphologic data, BNP levels and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure and decompensated HF. Passive left ventricular (LV) pressure-volume relations were determined in vitro. Transmural specimens from the anterior LV freewall were imaged using extended-volume confocal microscopy and 3D myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 months and increased progressively thereafter. However, it was less than control for filling pressures <10 mmHg and not significantly different above this. Myocyte cross-section was enlarged with increased variability from 12 months, while collagen fraction increased progressively. Perimysial collagen fraction remained unchanged with age, although endomysial collagen increased from 12 months. Perimysial collagen between adjacent muscle layers fused at 12 months and continued to thicken subsequently, while muscle layers became more dispersed and disordered. We conclude that LV dilatation which accompanies decompensated HF in this model of HHD is not due to LV "softening". While perimysial (and endomysial) collagen networks are substantially remodeled, they are not dissolved as has been proposed. We argue that progressive disruption of the laminar organization of LV myocardium may contribute to impaired systolic function in HHD.
Ian John Legrice; Adèle J Pope; Gregory B Sands; Gillian Whalley; Robert Neil Doughty; Bruce H Smaill
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-21
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Auckland University.
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