A Minimal-Invasive Approach for Standardized Induction of Myocardial Infarction in Mice

Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment of cardiac function, including either systolic dysfunction, diastolic dysfunction, or both. Several factors chronically lead to HF, including cardiac volume and pressure overload that may result from hypertension, valvular lesions, acute, or chronic ischemic injuries. Major forms of HF include hypertrophic, dilated, and restrictive cardiomyopathy. The severity of cardiomyopathy can be impacted by other comorbidities such as diabetes or obesity and external stress factors. Age is another major contributor, and the number of patients with HF is rising worldwide in part due to an increase in the aged population. HF can occur with reduced ejection fraction (HF with reduced ejection fraction), that is, the overall cardiac function is compromised, and typically the left ventricular ejection fraction is lower than 40%. In some cases of HF, the ejection fraction is preserved (HF with preserved ejection fraction). Animal models play a critical role in facilitating the understanding of molecular mechanisms of how hearts fail. This review aims to summarize and describe the strengths, limitations, and outcomes of both small and large animal models of HF with reduced ejection fraction that are currently used in basic and translational research. The driving defect is a failure of the heart to adequately supply the tissues with blood due to impaired filling or pumping. An accurate model of HF with reduced ejection fraction would encompass the symptoms (fatigue, dyspnea, exercise intolerance, and edema) along with the pathology (collagen fibrosis, ventricular hypertrophy) and ultimately exhibit a decrease in cardiac output. Although countless experimental studies have been published, no model completely recapitulates the full human disease. Therefore, it is critical to evaluate the strength and weakness of each animal model to allow better selection of what animal models to use to address the scientific question proposed.

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“…This technique reduces mortality due to shorter surgery time and guarantees higher reproducibility. 49…”

Section: Animal Models Of Hfrefmentioning

confidence: 99%

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Pilz

Chang

Kiss

et al. 2022

Circulation Research

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“…Using non-invasive models such as the recently described echocardiography-assisted technique for MI induction in mice might be preferable. 70 Moreover, it might be interesting to study their function in other models of cardiac disease, e.g. using a Cre-inducible diphtheria toxin receptor mouse model for targeted necrosis of cardiomyocytes or angiotensin II infusion-induced remodelling.…”

Section: Innate and Adaptive Immunity In Ischaemic Cardiac Diseasementioning

confidence: 99%

Immune cells in cardiac homeostasis and disease: emerging insights from novel technologies

Steffens

Nahrendorf

Madonna

2021

European Heart Journal

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The increasing use of single-cell immune profiling and advanced microscopic imaging technologies has deepened our understanding of the cardiac immune system, confirming that the heart contains a broad repertoire of innate and adaptive immune cells. Leucocytes found in the healthy heart participate in essential functions to preserve cardiac homeostasis, not only by defending against pathogens but also by maintaining normal organ function. In pathophysiological conditions, cardiac inflammation is implicated in healing responses after ischaemic or non-ischaemic cardiac injury. The aim of this review is to provide a concise overview of novel methodological advancements to the non-expert readership and summarize novel findings on immune cell heterogeneity and functions in cardiac disease with a focus on myocardial infarction as a prototypic example. In addition, we will briefly discuss how biological sex modulate the cardiac immune response. Finally, we will highlight emerging concepts for novel therapeutic applications, such as targeting immunometabolism and nanomedicine.

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“…Thus, this model allows investigation of the cellular and molecular mechanisms following tissue injury and wound healing. With increased haemodynamic load following sudden cardiomyocyte necrosis, contractile dysfunction and thinning of the LV posterior wall can be observed as early as 1 day after MI (Fattah et al, 2016; Sicklinger et al, 2020). Activation of multiple intracellular signalling cascades (Prabhu & Frangogiannis, 2016) and adverse cardiac remodelling leads to the initiation of asymmetrical LV remodelling that includes the key hallmarks of human MI including thinning of the LV free wall, thickening of the septal non‐ischaemic LV wall (Lindsey, Kassiri, et al, 2018), increased wall stress leading to progressive dilation, expansion of the scar and deterioration of cardiac function.…”

Section: In Vivo Models Of MImentioning

confidence: 99%

“…This results in precise borders between the IZ and RZ, rather than having a BZ with damaged yet viable and variably oxygenated cardiomyocytes, as in the LAD method (Ciulla et al, 2004; van den Bos et al, 2005). Recently, a minimally invasive method of electrical ablation describes ultrasound‐guided, coronary artery coagulation, using precise micromanipulator‐controlled high‐frequency electricity (Sicklinger et al, 2020). Requiring expertise in imaging, this closed‐chest approach (no thoracotomy or intubation required) allows immediate assessment of cardiac function after injury and reports similar LV dysfunction and infarct size as LAD ligation, but with lower welfare concerns and higher survival rates (Sicklinger et al, 2020).…”

Section: In Vivo Models Of MImentioning

confidence: 99%

“…Cardiac troponin I (cTnI) and T (cTnT) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are the most common biomarkers used to confirm experimental MI (Sicklinger et al, 2020; Sun et al, 2018). cTnI and cTnT are regulatory proteins that control the Ca 2+ ‐mediated contraction of cardiomyocytes, with predominant expression in the myocardium (Park et al, 2017).…”

Section: Cardiac Phenotyping After MImentioning

confidence: 99%

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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 Minimal-Invasive Approach for Standardized Induction of Myocardial Infarction in Mice

Cited by 9 publications

References 1 publication

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Immune cells in cardiac homeostasis and disease: emerging insights from novel technologies

Preclinical models of myocardial infarction: from mechanism to translation

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