Cardiovascular Journal of Africa: Vol 27 No 3 (May/June 2016)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016 134 AFRICA
Changes in cardiac structure and function in a modified
rat model of myocardial hypertrophy
Wenjun Dai, Qi Dong, Minsheng Chen, Luning Zhao, Ailan Chen, Zhenci Li, Shiming Liu
Abstract
Aim: In this study we designed a modified method of abdomi-
nal aortic constriction (AAC) in order to establish a stable
animal model of left ventricular hypertrophy (LVH). We also
evaluated cardiac structure and function in rats with myocar-
dial hypertrophy using echocardiography, and provide a theo-
ry and experimental basis for the application of drug interven-
tions using the LVH animal model. We hope this model will
provide insight into novel clinical therapies for LVH.
Methods: The abdominal aorta of male Wistar rats (80–100
g) was constricted between the branches of the coeliac
and anterior mesenteric arteries, to a diameter of 0.55
mm. Echocardiography, using a linear phase array probe,
combined with histology and plasma BNP concentration, was
performed at three, four and six weeks post AAC.
Results: The acute (24-hour) mortality rate was lower (8%)
than in previous reports (15%) using this modified rat model.
Compared with shams, animals who underwent AAC demon-
strated significantly increased interventricular septal (IVS),
LV posterior wall (LVPWd), LV mass index (LVMI), cross-
sectional area (CSA) of myocytes, and perivascular fibrosis;
while the ejection fraction (EF), fractional shortening (FS)
and cardiac output (CO) were consistently lower at each time
interval. Notably, differences in these parameters between
the AAC and sham groups were significant by three weeks
and reached a peak at four weeks. Following AAC, plasma
B-type natriuretic peptide (BNP) level was gradually elevated,
compared with the sham group, between three and six weeks.
Conclusion: This modified AAC model induced LVH both
stably and safely by week four post surgery. Echocardiography
was accurately able to assess changes in chamber dimensions
and systolic properties in the rats with LVH.
Keywords: AAC, myocardial hypertrophy, echocardiography, rat
Submitted 20/1/13, accepted 2/7/15
Cardiovasc J Afr 2016; 27: 134–142
DOI: 10.5830/CVJA-2015-053
The development of left ventricular hypertrophy (LVH) is an
adaptive response to pressure overload. Clinically, sustained
hypertrophy is correlated with an increase in incidence of
cardiovascular disease (CVD)-mediatedmortality, and is often the
initial step in the progression to congestive heart failure. Cardiac
hypertrophy is also a risk factor for arrhythmia and sudden
cardiac death. In order to develop therapeutic approaches to
prevent LVH, it is important to elucidate the precise mechanisms
and time course of the development of LVH.
Animal models of hypertrophy are critically important for
studies on the pathogenesis of LVH, its pathological processes
and therapeutic strategies for treatment and/or prevention
of LVH. Abdominal aortic constriction (AAC) is the most
widely used strategy to induce pressure overload leading to
compensatory myocardial hypertrophy.
Several important factors may affect the time course and
progression of myocardial hypertrophy caused by pressure
overload, such as species and age of animals, anatomical sites of
constriction, overload duration, and the degree of stenosis. 1,2 In
previous studies, most investigators constricted the abdominal
aorta above the left renal artery in adult rats. Based on the
anatomy of the abdominal aorta in rats, there are two large
arterial branches anterior to the left renal artery, the coeliac
and anterior mesenteric arteries. The constriction site relative
to these arterial branches may affect progression to myocardial
hypertrophy.3-6 Recent reports have noted that younger animals
fare better than adults following the AAC procedure,2 since
younger animals may have a narrower abdominal aorta, leading
to suboptimal restriction and less myocardial hypertrophy and
AAC-mediated surgical mortality.
In this study, we modified the traditional methods of AAC to
evaluate banding severity, banding location, age and time course.
We also explored an optimal method to induce myocardial
hypertrophy in rats. To date, most studies have used small-
animal echocardiographic systems or clinical echocardiography
instruments coupled with miniature transducers to detect
ventricular structural and functional changes in rats. This
specialised equipment increases the cost of experiments.2-4,7
In order to reduce these costs, we evaluated the possibility of
using a standard human ultrasound probe, which is commonly
Department of Cardiology, The Second Affiliated Hospital
of Guangzhou Medical University, Guangzhou, China
Wenjun Dai, MD
Shiming Liu, MD
Department of Physiology, Guangzhou Medical University,
Guangzhou, China
Qi Dong, MD
Guangzhou Institute of Cardiovascular Disease,
Guangzhou, China
Minsheng Chen, MM,
Wenjun Dai, MD
Shiming Liu, MD
Department of Medical Experimental Centre, Guangzhou
Medical University, Guangzhou, China
Luning Zhao, MB BS
Department of Cardiology, The First Affiliated Hospital of
Guangzhou Medical University, Guangzhou, China
Ailan Chen, MD
Department of Cardiology, The First Municipal People’s
Hospital of Guangzhou affiliated to Guangzhou Medical
College, Guangzhou, China
Zhenci Li, MD