Name: a cryoinjury model to study myocardial infarction in the mouse
Uploaded: 2019-09-19T14:30:00
Description: Watch this Scientific Journal Video about A Cryoinjury Model to Study Myocardial Infarction in the Mouse at JoVE.com

We thank Christiane Pahrmann for her technical assistance. D.W. was supported by the Max Kade Foundation. T.D. received grants from the Else Kro&#776;ner Fondation (2012_EKES.04) and the Deutsche Forschungsgemeinschaft (DE2133/2-1_. S. S. received research grants from the Deutsche Forschungsgemeinschaft (DFG; SCHR992/3- 1, SCHR992/4-1).

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
<ol>
	<li>Obtain mice at the age of 14 weeks weighing approximately 27 g (e.g., from the Institute of La...

<ol>
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C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+murine+closed-chest+model+of+myocardial+ischemia+and+reperfusion.">A murine closed-chest model of myocardial ischemia and reperfusion.</a> Journal of Visualized Experiments : JoVE. (65), e3896 (2012).</li><li>Antonio, E. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Left+ventricle+radio-frequency+ablation+in+the+rat:+a+new+model+of+heart+failure+due+to+myocardial+infarction+homogeneous+in+size+and+low+in+mortality.">Left ventricle radio-frequency ablation in the rat: a new model of heart failure due to myocardial infarction homogeneous in size and low in mortality.</a> J Card Fail. 15 (6), 540-548 (2009).</li><li>Ovsepyan, A. 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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...

Acute coronary syndrome (ACS) is the leading causes of death in the Western world1,2. 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 failure4,5. Despite recent advances in the treatment of ACS, the prevalence of ACS and ACS-related heart failure is rising, and therapeutic options are limited6,7. Therefore, developing animal models to study ACS and its complications are of immense interest.
To date, the most widely used animal model to study ACS and ACS-induced myocardial remodeling is the ligation of the left descending coronary artery (LAD). Ligation of the LAD leads to acute ischemia of the myocardium, similar to human myocardial tissue during ACS.&#160; However, inconsistent infarct sizes remain the Achilles&#39;&#160;heel of LAD ligation. Surgical variation and anatomical variability of the LAD lead to inconsistent infarct sizes and hinder the reproducibility and replicability of this procedure8,9,10. In addition, LAD ligation has a high intra- and postsurgical mortality. Despite recent endeavors to improve reproducibility and reduce mortality11,12, large numbers of animals are still needed to properly evaluate anti-remodeling therapies.
Alternative models of ACS have been proposed and studied over the recent years, including radio-frequency13, thermal14 or cryogenic injuries15,16,17,18. Current cryoinjury methods apply a metal rod pre-cooled in liquid nitrogen to damage the subject&#39;s cardiac tissue15,16. However, this procedure needs to be repeated several times to generate a sufficient infarct size. Due to the high conductivity and low heat capacity of the rod compared to the tissue, the probe warms quickly, and the tissue is cooled (and thus infarcted) heterogeneously. To overcome these limitations, we describe herein a cryoinfarction model utilizing a hand-held liquid nitrogen delivery system. This model is reproducible, easy to perform and can be established fast and reliably. A reproducible transmural infarct lesion independent of coronary anatomy is generated, which eventually leads to cardiac failure. This method is especially suitable to study the remodeling process for the evaluation of novel therapeutic pharmacological and tissue engineering-based strategies.

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a cryoinjury model to study myocardial infarction in the mouse

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.

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 (<strong class="xfi...

Watch this Scientific Journal Video about A Cryoinjury Model to Study Myocardial Infarction in the Mouse at JoVE.com

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

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

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we ...

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