Animal models

Various acute and chronic heart failure pig models are available in our laboratory. These models are useful to evaluate therapeutic efficacy and safety of new drug, cell, and device therapies before testing in humans.


Myocardial infarction

Myocardial infarction (MI) models are the most frequently used model in our laboratory. Fine-tuned control of MI induction procedure developed over the years offer acute survival rate > 90% even with proximal LAD (left anterior descending artery) occlusion. The animals exhibit significant reduction in systolic function with cardiac remodeling.

MI is induced in a catheter-based closed-chest manner. Size of infarction can be controlled by occluding different location of the coronary arteries.

See refs for detailed characteristics.

Chronic ischemia with hibernating myocardium

Gradual occlusion of the coronary arteries are common in clinical patients and the heart exhibits different characteristics compared to acute MI. The ischemic tissue does not contract normally because of ischemia, but are still viable. We developed a model that has similar myocardial characteristics.

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Mitral regurgitation (Volume overload)

Mitral valve regurgitation (MR) is one of the most frequent valve diseases in clinics. MR causes volume overload of the heart and induces left ventricular dilation. Systolic function is initially maintained, but eventually deteriorates. Our model shows significant left ventricular and left atrial dilation. Right ventricular failure  and pulmonary hypertension is commonly found in when MR is severe.

The model induction procedure is a catheter-based approach. This model is useful for studies in non-ischemic heart failure and testing devices for mitral valve repair.

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Aortic Banding (Pressure overload)

Hypertension is closely associated with cardiac diseases. Hypertension increases the pressure afterload of the heart and can lead to cardiac remodeling, such as hypertrophy and fibrosis. The aortic banding model shows significant hypertrophy of the heart including hypertrophy of individual cardiomyocytes, with mildly increased cardiac fibrosis. The model shows increased cardiac stiffness.

This is a surgical model, but we use left tracheotomy and surgery is very short (around 1 hour procedure) .

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Myocardial infarction + Aortic banding (Exaggerated cardiac remodeling)

Animal models generally have less cardiac remodeling in the non-ischemic tissue compared to patients with advanced heart failure, mainly due to the use of young animals without any comorbidities and short period of experimental studies. To create a large animal model of advanced heart failure, we combined MI and aortic banding. The model exhibited increased hypertrophy and remodeling in the non-ischemic myocardium compared to MI or aortic banding alone.

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Ischemic mitral regurgitation

MR is frequently found in patients after MI and is one of the predictors of worse clinical outcomes. It is well characterized that left circumflex MI in sheep commonly accompanies MR, but we did not find significant MR in pigs after left circumflex MI. Ischemic MR model was developed by occluding two coronary artery branches simultaneously.

This modes is created by catheter-based approach. Left circumflex artery and diagonal artery branch is occluded using two coronary balloons. The model exhibits significant MR and left atrial dilation at chronic phase.

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Pulmonary hypertension

Pulmonary hypertension accompanies right ventricular failure, which is the major determinant of patients prognosis. Injection of monochrotaline in rats and hypoxia in rodents are models commonly employed in basic research. However, there are few large animal models of pulmonary hypertension. In our lab, we developed and characterized pig models of pulmonary hypertension by pulmonary vein banding and pulmonary embolism. These models were useful in testing our new gene therapy effects and to translate it toward clinical.

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