Coronary Angiography During Ex-Situ Heart Perfusion in a Porcine Model
July 12th, 2024
Screening for coronary artery disease could increase the procurement of donor hearts with extended criteria. A protocol for performing reproducible coronary angiography during ex-situ heart perfusion is described herein in a porcine model.
Screening for coronary artery disease is recommended before heart procurement in marginal donors, but is often lacking. Performing a coronary angiographic imaging ex situ heart perfusion could be an alternative. This video provides a detailed description of this method.
Nonconventional views are needed for coronary imaging since the heart is inverted in the perfusion module. Second, the components of the module can create artifacts for inadequate imaging. And last, the toxicity of contrast agent remains questionable since it's not eliminated from the perfusion module.
Performing coronary angiographic imaging ex situ heart perfusion is easily reproducible and can exclude stenosis of the main coronary vessels. Coronary angiography on an insulated perfusion is not a common procedure for interventional cardiologist. Providing a detailed protocol of reproducible views can help to reduce exposure to contrast agent, which can be harmful.
A better assessment of coronary artery disease will increase the location of marginal grafts and could therefore reduce the organ shortage. To begin, use a scalpel to cut open the skin along the midline of an anesthetized pig. Open the subcutaneous tissue with a monopolar cautery.
Then use a semilunar sternal saw to open the sternum. Dissect and open the thymus. With a pair of Metzenbaum scissors, expose the pericardium.
Use 4/0 polypropylene sutures to perform purse string sutures on the right atrium and aortic root. Cannulate the right atrium with a 32 French 2 stage venous cannula. Now connect a previously heparinized sterilized bag to the right atrium cannula.
Collect 1, 500 milliliters of blood. Clamp the aorta, then infuse 1000 milliliters of cold cardioplegia solution. Next, remove the aortic and venous cannulas.
Section the left azygos vein, the two vena cavi, the distal ascending aorta, the pulmonary artery trunk, and the four pulmonary veins to excise the heart. Place the heart in cold saline solution. Check the aortic valve to confirm normal coaptation.
Place four pledgeted sutures around the distal section of the ascending aorta. Then insert the appropriate aortic cannula and fix it with a hose clamp. Next, insert a 30 French pulmonary artery cannula.
Secure it with a 4/0 purse string suture. Finally, place an intracardiac sump through the mitral orifice to vent the left ventricle. Elevate a perfusion machine by 25 centimeters with a platform.
Rotate it 90 degrees to the left. Prime the perfusion machine with 500 milliliters of priming solution. Then add 1, 500 milliliters of the collected porcine blood.
Oxygenate the blood with a membrane oxygenator. Then warm the blood to 34 degrees Celsius with a heater cooler. Collect an initial blood sample for blood gas analysis ionagram and lactate level.
Reduce the pump flow of the perfusion machine to 1000 milliliters per minute. Then remove the shunt between the aortic and venous lines. Now de air the aorta.
Connect the aortic cannula to the aortic line. Massage the heart gently until it is warmed. Place the heart for optimal normal thermic XC to perfusion.
Use an external pacemaker to pace the heart at 80 beats per minute. Slowly increase the pump flow to an aortic pressure of 65 milliliters of mercury. Close the inferior vena cava with a 4/0 polypropylene running suture.
Purge and connect the pulmonary artery cannula to the venous line to continuously assess coronary flow. Next, flush the 5 French introducer and the 5 French judkins right 3.5 coronary angiography catheter with serum. Insert a 5 French introducer through the valve orifice of the machine.
Advance the guide wire into the coronary angiography catheter up to the distal orifice. Then perform a coronary angiography. Catheterize the right coronary artery using the given views.
Then capture the images of the right coronary artery, proximal right coronary artery, and distal right coronary artery networks. Similarly, catheterize the left coronary artery and capture the images of the left anterior descending artery, spider view, and marginal coronary artery networks.
Overview
This article discusses a protocol for performing coronary angiography during ex-situ heart perfusion in a porcine model. The method aims to improve the screening for coronary artery disease in marginal heart donors, potentially increasing the availability of donor hearts.
Key Study Components
Area of Science
- Cardiology
- Transplantation
- Medical Imaging
Background
- Coronary artery disease screening is crucial for heart procurement.
- Marginal donors often lack adequate screening.
- Ex-situ heart perfusion offers a novel approach for imaging.
- Nonconventional views are necessary due to the heart's orientation in the perfusion module.
Purpose of Study
- To describe a reproducible method for coronary angiography.
- To assess the feasibility of this method in a porcine model.
- To address challenges related to imaging artifacts and contrast agent toxicity.
Methods Used
- Coronary angiographic imaging during ex-situ heart perfusion.
- Utilization of a porcine model for experimental validation.
- Evaluation of imaging artifacts caused by perfusion module components.
- Assessment of contrast agent toxicity in the perfusion environment.
Main Results
- The method provides detailed coronary imaging despite challenges.
- Artifacts were identified and addressed during the imaging process.
- Concerns regarding contrast agent toxicity were highlighted.
- The protocol shows promise for improving donor heart screening.
Conclusions
- Coronary angiography during ex-situ perfusion is feasible.
- This approach could enhance the procurement of donor hearts.
- Further studies are needed to optimize imaging techniques.
Frequently Asked Questions
Executive Industry Relevance
Coronary angiography during ex-situ heart perfusion in a porcine model addresses a critical gap in donor heart screening, particularly for extended criteria donors at risk for coronary artery disease. By enabling reproducible, quantitative coronary imaging outside the body, this protocol supports more confident graft selection and reduces the risk of primary graft failure. Integrating this approach at the procurement stage can enhance predictive confidence and optimize portfolio advancement decisions in transplantation research.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables direct interrogation of coronary artery patency in donor hearts prior to transplantation.
- Supports biological de-risking by identifying subclinical coronary lesions in marginal grafts.
- Facilitates functional validation of donor heart viability through quantitative imaging and lactate extraction metrics.
- Improves predictive confidence for downstream transplantation outcomes.
Screening & Assay Development
- Establishes standardized, reproducible imaging views for coronary assessment in ex-situ perfused hearts.
- Provides quantitative outputs such as contrast agent volume and lactate concentration for assay comparability.
- Enables reliable exclusion of significant coronary stenosis prior to graft acceptance.
- Supports scalability and platform reuse for broader donor screening initiatives.
Translational & Preclinical Research
- Aligns with disease-relevant models by simulating clinical donor heart evaluation workflows.
- Ensures continuity from preclinical imaging validation to translational transplantation protocols.
- Reduces biological risk in preclinical-to-clinical transition by standardizing viability assessment.
- Provides mechanistic de-risking for organ selection strategies.
Pipeline & Workflow Integration
This protocol integrates at the interface of donor heart procurement and preclinical transplantation validation, bridging early discovery with translational research.
- Discovery Biology: Supports hypothesis testing regarding coronary disease prevalence in marginal donors and clarifies viability thresholds.
- Screening: Delivers reproducible, quantitative coronary imaging outputs for standardized donor assessment.
- Analytics: Enables measurement of lactate extraction and contrast agent exposure to inform viability and safety decisions.
- Translational Research: Provides a workflow-aligned model for preclinical validation of donor heart selection criteria.
- Enterprise Reuse: Offers a reusable imaging and assessment protocol adaptable across donor models and research settings.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in donor heart selection and reduces mechanistic ambiguity in graft viability.
- Operational Value: Standardizes coronary imaging and viability assessment for reproducibility and scalability.
- Strategic Value: Enables more informed go/no-go decisions, improving capital efficiency and reducing late-stage biological risk in transplantation research.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of donor hearts for transplantation studies.
Implementation Considerations
- Requires expertise in interventional cardiology and ex-situ perfusion techniques.
- Demands access to specialized perfusion modules and imaging instrumentation.
- Necessitates cross-team standardization of imaging views and viability metrics.
- May require adaptation for different donor species or perfusion platforms.
- Contrast agent retention and imaging artifacts must be managed to ensure data quality.
