A Cryoinjury Model to Study Myocardial Infarction in the Mouse

Wang, Dong; Tediashvili, Grigol; Hu, Xiaomeng; Gravina, Alessia; Marcus, Sivan G.; Zhang, Hao; Olgin, Jeffrey E.; Deuse, T.; Schrepfer, Sonja

doi:10.3791/59958

Cited by 7 publications

(9 citation statements)

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“…In mice and rats, myocardial ischemia is induced surgically, either transiently by ischemia/reperfusion (I/R) injury 260,353 or complete occlusion by coronary artery ligation 261,354 or cryoinjury. 262,353,355 Unlike complete occlusion, I/R injury produces reversible ischemia that leads to significant myocardial dysfunction without widespread necrosis in the area at risk. Spontaneous ventricular arrhythmias are observed during the reperfusion phase.…”

Section: Animal Models Of Acquired Arrhythmia Disordersmentioning

confidence: 99%

Animal Models to Study Cardiac Arrhythmias

Blackwell

Schmeckpeper

Knollmann

2022

Circulation Research

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Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide, accounting for 10% to 15% of all deaths. Although most arrhythmias are due to acquired heart disease, inherited channelopathies and cardiomyopathies disproportionately affect children and young adults. Arrhythmogenesis is complex, involving anatomic structure, ion channels and regulatory proteins, and the interplay between cells in the conduction system, cardiomyocytes, fibroblasts, and the immune system. Animal models of arrhythmia are powerful tools for studying not only molecular and cellular mechanism of arrhythmogenesis but also more complex mechanisms at the whole heart level, and for testing therapeutic interventions. This review summarizes basic and clinical arrhythmia mechanisms followed by an in-depth review of published animal models of genetic and acquired arrhythmia disorders.

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Section: Animal Models Of Acquired Arrhythmia Disordersmentioning

confidence: 99%

Animal Models to Study Cardiac Arrhythmias

Blackwell

Schmeckpeper

Knollmann

2022

Circulation Research

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“…The cryo-injury model involves a thoracotomy, pericardiectomy and cryo-infarction performed using a cryoprobe (3 mm for mouse, 9 mm for rat) applied to the anterior LV free wall for 10s, using positioning of the left atrium and pulmonary artery for guidance 54 . This method initiates comparable decline in LV function as using the LAD ligation method, albeit with reduced cardiac remodelling, smaller and thicker scar formation and improved survival rates 55 . Interestingly, scar formation is not fully resolved after cryoinjury 56 and differences to the MI model may be instructive in understanding the pathophysiology of the scar region.…”

Section: Ablation Methodsmentioning

confidence: 98%

Preclinical models of myocardial infarction: from mechanism to translation

Martin

Macdonald

Elbassioni

et al. 2021

British J Pharmacology

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Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Pre-clinical animal models have significantly advanced our understanding of MI and enable the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in pre-clinical animal models. Despite this, pre-clinical models are limited in their ability to fully recapitulate the complexity of MI in humans. The pre-clinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action (MOA) and support translational medicine development.

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“…A recently developed cryoinjury model was used ( 55 ). Briefly, after induction of analgesia and anesthesia, the mice were intubated and a right thoracotomy was performed.…”

Section: Methodsmentioning

confidence: 99%

Hypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice

Deuse

Tediashvili

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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The emerging field of regenerative cell therapy is still limited by the few cell types that can reliably be differentiated from pluripotent stem cells and by the immune hurdle of commercially scalable allogeneic cell therapeutics. Here, we show that gene-edited, immune-evasive cell grafts can survive and successfully treat diseases in immunocompetent, fully allogeneic recipients. Transplanted endothelial cells improved perfusion and increased the likelihood of limb preservation in mice with critical limb ischemia. Endothelial cell grafts transduced to express a transgene for alpha1-antitrypsin (A1AT) successfully restored physiologic A1AT serum levels in mice with genetic A1AT deficiency. This cell therapy prevented both structural and functional changes of emphysematous lung disease. A mixture of endothelial cells and cardiomyocytes was injected into infarcted mouse hearts, and both cell types orthotopically engrafted in the ischemic areas. Cell therapy led to an improvement in invasive hemodynamic heart failure parameters. Our study supports the development of hypoimmune, universal regenerative cell therapeutics for cost-effective treatments of major diseases.

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A Cryoinjury Model to Study Myocardial Infarction in the Mouse

Cited by 7 publications

References 0 publications

Animal Models to Study Cardiac Arrhythmias

Animal Models to Study Cardiac Arrhythmias

Preclinical models of myocardial infarction: from mechanism to translation

Hypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice

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