A Cryoinjury Model to Study Myocardial Infarction in the Mouse

Summary

This article demonstrates a model to study cardiac remodeling after myocardial cryoinjury in mice.

Abstract

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we demonstrate a murine cryoinjury infarct model that generates precise infarct sizes with high reproducibility and replicability. In brief, after intubation and sternotomy of the animal, the heart is lifted from the thorax. The probe of a handheld liquid nitrogen delivery system is applied onto the myocardial wall to induce cryoinjury. Impaired ventricular function and electrical conduction can be monitored with echocardiography or optical mapping. Transmural myocardial remodeling of the infarcted area is characterized by collagen deposition and loss of cardiomyocytes. Compared to other models (e.g., LAD-ligation), this model utilizes a handheld liquid nitrogen delivery system to generate more uniform infarct sizes.

Introduction

Acute coronary syndrome (ACS) is the leading causes of death in the Western world^1,2. Acute occlusion of the coronary arteries leads to activation of ischemic cascade and necrosis of the affected cardiac tissue³. Damaged myocardium is gradually replaced by non-contractile scar tissue, which manifestz clinically as a heart failure^4,5. Despite recent advances in the treatment of ACS, the prevalence of ACS and ACS-related heart failure is rising, and therapeutic options are limited^6,

Protocol

Animals received humane care in compliance with the Guide for the Principles of Laboratory Animals, prepared by the Institute of Laboratory Animal Resources, and published by the National Institutes of Health. All animal protocols were approved by the responsible local authority (the University of California San Francisco (UCSF) Institutional Animal Care and Use Committee).

1. Animal care

1. Obtain mice at the age of 14 weeks weighing approximately 27 g (e.g., from the Institute of Laboratory Animals).
   NOTE: BALB/c mice are used for this article.
2. Keep mice under conventional conditions in ventilated cabinets, feedi....

Results

The cryoinjury infarct model is suitable to study ACS and its complications. Low mortality rates and efficient postsurgical recovery is seen in this model. Cryoinjury induced myocardial damage leads to reduced cardiac function, electrical uncoupling, and transmural remodeling.

Echocardiography can be used to monitor cardiac function noninvasively in vivo. In cryo-injured hearts, echocardiography demonstrates significantly reduced ejection fraction and fractional area change (

Discussion

This article describes a mouse cryoinjury model to investigate ACS and related pharmacological and therapeutic options.

The most crucial step is the application of the cryoprobe on the cardiac tissue. Contact duration must be tightly controlled in order to obtain the optimal infarct size and to guarantee reproducible results. Prolonged cooling of the myocardium will lead to oversized infarcts or ventricular perforation. In contrast, shortened cooling time generates limited epicardial lesions a.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
10 ml Syringe	Thermo Scientific	03-377-23
5-0 prolene suture	Ethicon	EH7229H
6-0 prolene suture	Ethicon	8706H
8-0 Ethilon suture	Ethicon	2808G
Absorption Spears	Fine Science Tools	18105-01
BALB/c	The Jackson Laboratory	Stock number 000651
Bepanthen Eye and Nose ointment	Bayer	1578675	Eye ointment
Betadine Solution	Betadine Purdue Pharma	NDC:67618-152
Blunt Forceps	Fine Science Tools	18025-10
Buprenex	Reckitt Benckiser	NDC Codes: 12496-0757-1, 12496-0757-5	Buprenorphine
Cryoprobe 3mm	Brymill Cryogenic Systems	Cry-AC-3 B-800
Ethanol 70%	Th. Geyer	2270
Forceps curved	S&T	00284
Forceps fine	Fine Science Tools	11251-20
Forceps standard	Fine Science Tools	11023-10
Gross Anatomy Probe	Fine Science Tools	10088-15
Hair clipper	WAHL	8786-451A ARCO SE
High temperature cautery kit	Bovie	18010-00
ISOFLURANE	Henry Schein Animal Health	029405
IV Catheter 20G	B. Braun	603028
Mini-Goldstein Retractor	Fine Science Tools	17002-02
NaCl 0.9%	B.Braun	PZN 06063042          Art. Nr.: 3570160	saline
Needle holder	Fine Science Tools	12075-14
Needle Holder, Curved	Harvard Apparatus	72-0146
Novaminsulfon	Ratiopharm	PZN 03530402	Metamizole
Operating Board	Braintree Scientific	39OP
Replaceable Fine Tip	Bovie	H101
Scissors	Fine Science Tools	14028-10
Small Animal Ventilator	Kent Scientific	RV-01
Spring Scissors - Angled to Side	Fine Science Tools	15006-09
Surgical microscope	Leica	M651
Transpore Surgical Tape	3M	1527-1
Vannas Spring Scissors	Fine Science Tools	15400-12
Vaporizer	Kent Scientific	VetFlo-1205S