Transverse Aortic Constriction in Mice

Summary

Transverse aortic constriction (TAC) in the mouse is a commonly used experimental model to study mechanisms underlying cardiac hypertrophy and heart failure development. Here, we describe procedures to constrict the aorta to create a reproducible degree of cardiac hypertrophy in mice.

Abstract

Transverse aortic constriction (TAC) in the mouse is a commonly used experimental model for pressure overload-induced cardiac hypertrophy and heart failure.¹ TAC initially leads to compensated hypertrophy of the heart, which often is associated with a temporary enhancement of cardiac contractility. Over time, however, the response to the chronic hemodynamic overload becomes maladaptive, resulting in cardiac dilatation and heart failure.² The murine TAC model was first validated by Rockman et al.¹, and has since been extensively used as a valuable tool to mimic human cardiovascular diseases and elucidate fundamental signaling processes involved in the cardiac hypertrophic response and heart failure development. When compared to other experimental models of heart failure, such as complete occlusion of the left anterior descending (LAD) coronary artery, TAC provides a more reproducible model of cardiac hypertrophy and a more gradual time course in the development of heart failure. Here, we describe a step-by-step procedure to perform surgical TAC in mice. To determine the level of pressure overload produced by the aortic ligation, a high frequency Doppler probe is used to measure the ratio between blood flow velocities in the right and left carotid arteries.^{3, 4} With surgical survival rates of 80-90%, transverse aortic banding is an effective technique of inducing left ventricular hypertrophy and heart failure in mice.

Protocol

Part 1: Preparation of Operating Field

1. The operating field is disinfected with 75% isopropyl alcohol.
2. Make sure the heating pad is on and at the right temperature. A recommended system is a Gaymar circulating water pump connected to a therapy pad that is maintained at 37 °C ± 1 °C. It is important to maintain normal body temperature during surgery as to avoid a rapid decrease in heart rate.
3. Surgical tools are sterilized in a hot bead sterilizer before surgery. For this procedure, you will need the following surgical instruments: blunt scissors, course curved forceps X 2, fine 45° angled forceps X 2, angled spring scissors, chest retrac....

Discussion

TAC, which mimics human aortic stenosis, is a common method to induce cardiac hypertrophy and heart failure in mice. Alternative sites for aortic constriction include the ascending and abdominal aorta. Ascending aortic constriction provides an extreme and more rapid overload on the left ventricle (LV). In contrast, abdominal aortic constriction leaves intact a larger portion of the circulation as a means of possible compensation.⁸ Therefore, TAC is often the preferred model as it provides for adequate LV overl.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Gaymar T/pump	Harvard Apparatus	Model TP-500	Circulating water pump
Temp. therapy pads	Harvard Apparatus	60-3414
Hot bead sterilizer	Fine Science Tools	18000-45
Blunt scissors	Roboz Surgical Instruments Co.	RS-5980
Angled spring scissors	Roboz Surgical Instruments Co.	RS-5668
Chest retractor	Fine Science Tools	17002-02
Course curved forceps	Roboz Surgical Instruments Co.	RS-5138
Dumont fine 45° angled forceps	Fine Science Tools	11253-25
Needle holder	Fine Science Tools	12565-14
Electric shaver	GE Healthcare		For shaving mouse fur
PE 90 tubing	BD Biosciences	427420	For intubation
MiniVent (ventilator)	Harvard Apparatus	Type 845
Betadine	Fisher Scientific	19-027132	May be purchased at medical supply store
Sterile gloves	Mckesson	20-1565
Stereo microscope	Unico	ZM186
6-0 silk suture	Fine Science Tools	18020-60
27 ½ gauge needle	BD Biosciences	305109
6-0 prolene suture	Mckesson	3286
Buprenorphine	Institutional Animal Facility