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 The operating field is disinfected with 75% isopropyl alcohol. 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. Surgical tools are sterilized in a hot bead sterilizer before surgery. For this proc…

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

Material Name	Tipo	Company	Catalogue Number	Comment
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	RS-5980
Angled spring scissors		Roboz	RS-5668
Chest retractor		Fine Science Tools	17002-02
Course curved forceps		Roboz	RS-5138
Dumont fine 45° angled forceps		Fine Science Tools	11253-25
Needle holder		Fine Science Tools	12565-14
Electric shaver		General Electric		For shaving mouse fur
PE 90 tubing		BD	427420	For intubation
MiniVent (ventilator)		Harvard Apparatus	Type 845
Betadine		Fisher	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	305109
6-0 prolene suture		Mckesson	3286
Buprenorphine		Institutional Animal Facility