A transmural gradient of myocardial remodeling in early-stage heart failure with preserved ejection fraction in the pig.


Journal

Journal of anatomy
ISSN: 1469-7580
Titre abrégé: J Anat
Pays: England
ID NLM: 0137162

Informations de publication

Date de publication:
03 2020
Historique:
accepted: 15 10 2019
pubmed: 22 11 2019
medline: 11 3 2021
entrez: 22 11 2019
Statut: ppublish

Résumé

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction. This study aimed to analyze whether early HFpEF is already associated with ultrastructural alterations and whether they differ quantitatively among the layers of the left ventricular wall. HFpEF was induced in pigs by deoxy-corticosterone acetate (DOCA) treatment along with a high-salt/high lipid diet over 3 months and compared with weight-matched normal pigs (n = 5 each). Samples of the left ventricle were taken and processed for light and electron microscopy. Interstitial fibrosis, subcellular composition of cardiomyocytes and mean cardiomyocyte diameter were evaluated by stereology in subendocardial, midmyocardial and subepicardial regions. DOCA enhanced the mean cardiomyocyte diameter in all locations of the ventricle wall to the same degree. The subcellular composition did not differ between the locations and was not altered by DOCA. The volume fraction of interstitium was smaller in the subendocardium of DOCA group than of control group. Within the interstitium, the volume fraction of collagen fibrils (between cardiomyocytes) was increased in the subendocardial and midmyocardial wall layers of the DOCA group but not in the subepicardial layer. Although the capillary length density and average supply area were not altered in response to DOCA in any of the wall layers, the volume fraction of blood vessels related to the interstitial space was enhanced in the subendocardium of the DOCA group but not in the other wall layers. In conclusion, cardiomyocyte changes due to DOCA were similar in subepicardial, midmyocardial and subendocardial regions but DOCA-induced changes in the interstitium appeared to be more pronounced in the subendocardial ventricular wall layers. This suggests a pivotal role of the subendocardial interstitium in the pathogenesis of HFpEF.

Identifiants

pubmed: 31749243
doi: 10.1111/joa.13117
pmc: PMC7018631
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

531-539

Informations de copyright

© 2019 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

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Auteurs

Christian Mühlfeld (C)

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany.
German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.

Alexandra Rajces (A)

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Martin Manninger (M)

Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria.

Alessio Alogna (A)

Department of Cardiology, Charité University Medicine, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.

Marie-Christin Wierich (MC)

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Daniel Scherr (D)

Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria.
Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.

Heiner Post (H)

Department of Cardiology, Contilia Heart and Vessel Centre, St. Marien-Hospital Mülheim, Mülheim, Germany.

Julia Schipke (J)

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany.
German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.

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