A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep

作者： Rei Ukita1, John W. Stokes1, W. Kelly Wu1, Jennifer Talackine1, Nancy Cardwell1, Yatrik Patel1, Clayne Benson5, Caitlin T. Demarest1, Erika B. Rosenzweig3, Keith Cook2, Emily J. Tsai4, Matthew Bacchetta1,6 1Department of Thoracic Surgery,Vanderbilt University Medical Center, 2Department of Biomedical Engineering,Carnegie Mellon University, 3Department of Pediatrics,Columbia University Medical Center, Columbia University Irving Medical Center, 4Department of Medicine,Columbia University Medical Center, Columbia University Irving Medical Center, 5Department of Anesthesiology,Vanderbilt University Medical Center, 6Department of Biomedical Engineering,Vanderbilt University

简介：

Overview

This manuscript describes a large animal model for studying right ventricular adaptation and failure, which is crucial for developing RV-targeted therapeutics for pulmonary hypertension. The model allows for controlled increases in right ventricular afterload, providing a unique approach to titrate RV adaptation.

Key Study Components

Area of Science

• Cardiovascular physiology
• Animal models
• Pulmonary hypertension

Background

• Right ventricular pressure overload is a significant factor in pulmonary hypertension.
• Understanding RV adaptation and failure is essential for therapeutic development.
• Previous models lacked control over RV phenotype adaptation.
• This study introduces a novel surgical technique for this purpose.

Purpose of Study

• To develop a model that simulates severe right ventricular pressure overload.
• To investigate adaptive and maladaptive phenotypes of the right ventricle.
• To facilitate the development of targeted therapies for pulmonary hypertension.

Methods Used

• Surgical procedure for pulmonary artery banding demonstrated by Dr. Matthew Bacchetta and surgical fellows.
• Progressive increase of right ventricular afterload to assess adaptation.
• Large animal model to ensure relevance to human physiology.
• Controlled experimental design to evaluate RV responses.

Main Results

• Successful implementation of the pulmonary artery banding technique.
• Establishment of a model that allows for titration of RV adaptation.
• Demonstration of the model's potential for studying RV failure.
• Insights into the adaptive and maladaptive responses of the right ventricle.

Conclusions

• The developed model provides a novel approach to studying right ventricular adaptation.
• This research is vital for advancing therapies for pulmonary hypertension.
• Future studies can leverage this model to explore RV-targeted interventions.

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