Heart Failure Models

Driving Innovation in Heart Failure Drug Discovery

Back to Pharmacology and Toxicology Assessment top page

Solutions for Heart Failure Drug Discovery

Heart failure is a complex and life-threatening syndrome characterized by the heart’s reduced ability to pump or fill with blood, leading to inadequate circulation. Affecting over 64 million people globally, heart failure remains a significant under met medical need and imposes a significant strain on health care systems. Its prevalence continues to rise due to aging and lack of fully effective therapies. Addressing this global challenge requires innovative solutions. As a preclinical discovery research organization, Inotiv offers translationally relevant rodent and large animal models coupled with flexible research services and consultation to accelerate heart failure drug discovery and the development of effective therapies. Our comprehensive in vivo pharmacology services are designed to deliver clinically relevant insights by providing robust data on therapeutic mechanisms and efficacy. Through consultation and close collaboration with clients, we generate customized experimental designs tailored to capitalize on the unique features of your target and related mechanisms.

In Vivo Models of Heart Failure

DILATED CARDIOMYOPATHY MODELS

Dilated cardiomyopathy is a disease of the heart muscle that leads to the progressive enlargement of the left ventricle, resulting in cardiac insufficiency and compromised cardiac output. In simple terms, Heart Failure with Reduced Ejection Fraction (HFrEF) is a condition where the heart is unable to pump blood effectively because of its compromised ability to contract and deliver adequate cardiac output. This condition typically develops gradually, often preceded by pathophysiological dysfunction of the heart before symptoms appear, presenting an opportunity for early intervention. Chronic heart failure can develop as the condition worsens, leading to a severe reduction in overall cardiac function. The 5-year survival rate for patients with untreated dilated cardiomyopathy is approximately 50%.

Key Models:

Myocardial Infarction Mouse and Rat Model
Myocardial Ischemia/Reperfusion Rat Model
Doxorubicin-Induced Dilated Cardiomyopathy Mouse Model
Norepinephrine-Induced Cardiac Dysfunction Mouse Model
Lipopolysaccharide (LPS)-Induced Dilated Cardiomyopathy Rat Model

DIABETIC CARDIOMYOPATHY MODELS

Diabetic cardiomyopathy refers to the association of diabetes mellitus with myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. As the occurrence of metabolic syndrome, and thus diabetes mellitus, increases, so does the incidence of diabetic cardiomyopathy. Diabetic cardiomyopathy can often lead to Heart Failure with preserved Ejection Fraction or HFpEF. It is initially characterized by myocardial fibrosis and dysfunctional remodeling, which manifests as diastolic dysfunction.

Key Models

ZSF1 Rat Model of Diabetic Cardiomyopathy
db/db AAV-Renin Mouse Model of Diabetic Cardiomyopathy

HYPERTROPHIC CARDIOMYOPATHY MODELS

Hypertrophic Cardiomyopathy (HCM) is a heart condition characterized by abnormal cardiomyocyte hypertrophy resulting in thickening of the ventricular wall. This is often due to genetic factors or conditions such as pressure overload hypertrophy from hypertension or aortic stenosis. This cardiac hypertrophy can obstruct blood flow and impair the heart's ability to pump efficiently. HCM is often associated with HFpEF, a condition in which the heart maintains its pumping ability but struggles to fill with an adequate amount of blood.

Key Models

DOCA-Salt Hypertrophic Cardiomyopathy Rat Model
Dahl-Salt Sensitive (DSS) Hypertrophic Cardiomyopathy Rat Model
Angiotensin II-Infused Mouse and Rat Model
Transverse Aortic Constriction (TAC) Mouse Model
Isoproterenol-Induced Hypertrophic Cardiomyopathy Mouse Model

Experimental Autoimmune Myocarditis Models

Experimental Autoimmune Myocarditis (EAM) is a heart condition characterized by an inflammation of the myocardium resulting from an autoimmune response with cardiac myosin as the autoantigen. EAM progresses from inflammation to the development of cardiac fibrosis and hypertrophy, ultimately leading to dilated cardiomyopathy and decompensated heart failure.

Key Models

βMHC-Induced EAM Mouse Model

Not seeing the model you need? Browse our comprehensive selection of in vivo models for Cardiovascular Disease drug discovery or reach out to discuss developing a custom model tailored to your needs. Our commitment to innovation drives the advancement of new models and the optimization of existing ones, ensuring sophisticated solutions that align with your research objectives.

Selected Study Endpoints

For preclinical drug discovery in heart failure, we offer a broad set of key endpoints to comprehensively assess therapeutic efficacy. Our models are designed to replicate clinically relevant aspects of heart failure, enabling in-depth evaluation of drug candidates. While the list below highlights some of our capabilities, we offer a wider range of services and work closely with clients to create customized study designs that align with specific research goals.

Systolic and diastolic cardiac ultrasound
Direct ventricular hemodynamic measurement
Systemic and renal hemodynamics
Comprehensive panel of cardiac biomarkers
Ex vivo myograph aortic ring assay

Comprehensive Services for Drug Development

At Inotiv, we provide comprehensive research services to support drug development from early discovery through IND filing. Our integrated approach enhances efficiency, ensuring a seamless progression from preclinical studies to regulatory submission. By combining scientific expertise with cutting-edge technology, we generate high-quality, translational data that informs critical decisions. Each program benefits from customized solutions tailored to its specific needs, helping to drive successful therapeutic advancements.