Background
Mechanisms involved in cardiac remodelling by aortic regurgitation (AR) and the moment
when cardiac dysfunction begins are largely unknown. This study aimed to investigate
cardiac morphology and function after 1, 4, 8, and 12 weeks of experimental AR in
Wistar rats. Extracellular matrix was also investigated as the potential mechanism
that underlies the AR remodelling process.
Methods
Male Wistar rats underwent surgical acute AR (AR group, n=51) or a sham surgery (sham
group, n=32). After the procedure, serial transthoracic echocardiograms were performed
at 1, 4, 8, and 12 weeks. Morphometry of cardiac tissue and the activities of metalloproteinase
2 (MMP-2) and tissue metalloproteinase inhibitor-1 (TIMP-1) were analysed. Statistical
analysis was performed by two-way ANOVA. Significance level was 5%.
Results
The AR group presented an increase in the sphericity index (week 1); an increase in
the left atrium, left ventricular mass index, TIMP-1 and MMP-2 activities, and collagen
fraction (week 4); an increase in myocyte area (week 8); and a reduction in fraction
shortening (week 12). First, the chamber became more spherical; second, MMP-2 and
TIMP-1 were activated and this may have contributed to hypertrophy and atrial enlargement,
until systolic dysfunction occurred.
Conclusions
This study showed a sequence of abnormalities that preceded myocardial dysfunction
in an experimental model of AR. First, haemodynamic volume overload led to a more
spherical left ventricle chamber. Second, MMP-2 and TIMP-1 transitorily increased
and may have contributed to atrial enlargement, eccentric hypertrophy, and systolic
dysfunction.
Keywords
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Article info
Publication history
Published online: January 13, 2022
Accepted:
November 22,
2021
Received in revised form:
November 8,
2021
Received:
August 10,
2021
Identification
Copyright
© 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
