A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Summary

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

Abstract

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

Introduction

Heart failure is a complex clinical syndrome, the symptoms of which include fatigue, dyspnea, exercise intolerance, and fluid retention in peripheral tissues. It is the leading cause of death in developed countries¹. Aside from inherited cardiomyopathy caused by mutations in sarcomere proteins or ion channels², myocardial dysfunction can be caused by a variety of medical conditions, including hypertension, valvular heart diseases, obesity, and diabetes³. Changes in myocardial structure, electrical conduction, and energy metabolism lead to inadequate cardiac pumping capacity to meet circulatory demands, which ultimately results in heart....

Protocol

All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals, published by the US National Institutes of Health (NIH publication no. 85-23, revised 1996). This protocol was approved by and in accordance with the guidelines set forth by the Institutional Animal Care and Use Committee at National Taiwan University.

1. Animal Surgery

1. Prepare a 22 G syringe needle by blunting the tip of the needle on a honing stone. Using pliers, plicate the needle to a right angle.
2. Before surgery, prepare the required surgical instruments and materials, as well as a recovery cage. Autoclave....

Results

10 weeks after the abdominal aortic constriction surgery, the resulting cardiac pathology was analyzed. The cardiac histology was measured by calculating the ratio of the heart weight to the body weight and by detecting the amount of collagen in the heart. Cardiac injury was confirmed by measuring plasma cardiac troponin concentration.

As shown in Figure 1A, the cardiac size was enlarged after abdominal aortic c.......

Discussion

Hypertensive heart disease, a major health problem that contributes greatly to morbidity and mortality, can lead to cardiac hypertrophy and heart failure⁵. The pathogenesis and progression of hypertensive heart disease in humans is complex, so an appropriate animal model is critical to investigate the underlying mechanisms and to test novel therapeutics that aim to improve cardiac structure and function⁵. The abdominal aortic constriction model, which simulates chronic heart disease, is an effective.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
22 G syringe needle	BD Biosciences	309572
EDTA Blood Collection Tubes	BD Biosciences	REF365974
4-0 silk suture	Sharpoint™ Products	DC-2515N
6-0 silk suture	Sharpoint™ Products	DC-2150N
Pentobarbital	Sigma Aldrich	1507002
Paraformaldehyde	Sigma Aldrich	441244
Acetaminophen	Sigma Aldrich	A7085
Picrosirius red solution	Abcam	ab150681
Cardiac troponin kit	Abcam	ab200016
Imagequant	Molecular Dynamics
Langendorff	ADInstruments	ML870B2