Large Animal Models of Heart Failure With Reduced Ejection Fraction (HFrEF)

Large Animal Models of Heart Failure: Reduced vs. Preserved Ejection Fraction

Animals ◽

10.3390/ani10101906 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1906 ◽

Cited By ~ 1

Author(s):

Christopher J. Charles ◽

Miriam T. Rademaker ◽

Nicola J. A. Scott ◽

A. Mark Richards

Keyword(s):

Heart Failure ◽

Clinical Trials ◽

Animal Models ◽

Ejection Fraction ◽

Treatment Options ◽

Large Animal ◽

Reduced Ejection Fraction ◽

Large Animal Models ◽

Sampling Protocols ◽

Underlying Mechanisms

Heart failure (HF) is the final common end point of multiple metabolic and cardiovascular diseases and imposes a significant health care burden worldwide. Despite significant improvements in clinical management and outcomes, morbidity and mortality remain high and there remains an indisputable need for improved treatment options. The pathophysiology of HF is complex and covers a spectrum of clinical presentations from HF with reduced ejection fraction (HFrEF) (≤40% EF) through to HF with preserved EF (HFpEF), with HFpEF patients demonstrating a reduced ability of the heart to relax despite an EF maintained above 50%. Prior to the last decade, the majority of clinical trials and animal models addressed HFrEF. Despite growing efforts recently to understand underlying mechanisms of HFpEF and find effective therapies for its treatment, clinical trials in patients with HFpEF have failed to demonstrate improvements in mortality. A significant obstacle to therapeutic innovation in HFpEF is the absence of preclinical models including large animal models which, unlike rodents, permit detailed instrumentation and extensive imaging and sampling protocols. Although several large animal models of HFpEF have been reported, none fulfil all the features present in human disease and few demonstrate progression to frank decompensated HF. This review summarizes well-established models of HFrEF in pigs, dogs and sheep and discusses attempts to date to model HFpEF in these species.

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Large animal models of heart failure with preserved ejection fraction

Heart Failure Reviews ◽

10.1007/s10741-021-10184-9 ◽

2021 ◽

Author(s):

Chihiro Miyagi ◽

Takuma Miyamoto ◽

Taiyo Kuroda ◽

Jamshid H. Karimov ◽

Randall C. Starling ◽

...

Keyword(s):

Heart Failure ◽

Animal Models ◽

Ejection Fraction ◽

Large Animal ◽

Preserved Ejection Fraction ◽

Large Animal Models

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Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53824 ◽

2011 ◽

Author(s):

Peter W. Walsh ◽

Craig S. McLachlan ◽

Leigh Ladd ◽

Arie Blitz ◽

R. Mark Gillies ◽

...

Keyword(s):

Heart Failure ◽

Animal Models ◽

Large Animal ◽

Failure Model ◽

Large Animal Models ◽

Surgical Model ◽

Coronary Ligation ◽

Rapid Ventricular Pacing ◽

Heart Failure Model ◽

Underlying Pathology

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

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