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Updated: Jan 18, 2026
Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment
Published on: May 10, 2022
Terminal Harvest Procedure of a Large Animal Model of Chronic Myocardial Ischemia with Hemodynamic Characterization
Kelsey C Muir1, Christopher Stone2, Dwight D Harris2
1Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert Medical School, Brown University; Cardiovascular Research Center, Rhode Island Hospital; kelsey_muir@brown.edu.
Insights
This study details a refined swine model for investigating chronic myocardial ischemia, crucial for advancing cardiovascular disease research. The protocol enables robust analysis of cardiac function and blood flow, aiding therapeutic development.
Area of Science:
- Cardiovascular Research
- Animal Models
- Translational Science
Background:
- Cardiovascular disease (CVD) presents a significant global health burden.
- Robust and validated animal models are essential for CVD research and therapeutic development.
- Reproducibility and research integrity are critical for scientific discovery.
Purpose of the Study:
- To detail a comprehensive cardiac analysis protocol in a swine model of chronic myocardial ischemia.
- To provide a validated methodology for researchers investigating cardiovascular disease (CVD).
- To improve and cultivate protocols for therapeutic investigation aimed at eliminating CVD.
Main Methods:
- A two-surgery protocol in a swine model, refined over 20 years.
- Induction of chronic myocardial ischemia via ameroid constrictor placement, mimicking human coronary artery disease (CAD).
- Comprehensive collection of cardiac hemodynamic parameters using left ventricular pressure-volume (PV) loop catheterization and isotope-labeled microspheres for myocardial blood flow analysis.
Main Results:
- The protocol allows for detailed assessment of cardiac hemodynamics and regional coronary perfusion.
- Isotope-labeled microspheres quantify collateralization in the ischemic area.
- Left ventricular pressure-volume (PV) loop catheterization provides a broad range of hemodynamic measurements.
Conclusions:
- The described swine model offers a robust platform for studying chronic myocardial ischemia.
- Detailed cardiac analysis, including hemodynamic parameters and myocardial blood flow, is crucial for therapeutic evaluation.
- Sharing this protocol can advance research and therapy development for cardiovascular disease.
Abstract:
Reproducibility and research integrity are foundational tenets to scientific discovery, which are produced utilizing well-established, proven principles and protocols. Furthermore, with the ever-increasing prevalence and burden cardiovascular disease (CVD) places on individuals and society at large, it deems essential to cultivate robust and validated model for investigation. Our group utilizes a two-surgery protocol in a swine model that has been progressively refined over the last twenty years, in which we first induce chronic myocardial ischemia by placement of an ameroid constrictor mimicking the pathophysiology of coronary artery disease (CAD) in humans. The second and terminal procedure is a comprehensive and thoughtful collection of cardiac hemodynamic parameters as well as regional coronary perfusion, followed by beating heart euthanasia and detailed sectioning of the heart. Our lab uses isotope-labeled microspheres to analyze myocardial blood flow to the ischemic area as a powerful method to quantify collateralization due to experimental therapeutic agents. Furthermore, and likely the most important measurable cardiovascular outcome, we utilize left ventricular pressure-volume (PV) loop catheterization to measure a broad range of hemodynamic parameters. We hope by detailing the comprehensive cardiac analysis of our swine model of chronic myocardial ischemia, other researchers may improve and cultivate their own protocols and therapy investigation for the elimination of cardiovascular disease.
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