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Published on: March 12, 2018
Insights into coronary collateral formation from a novel porcine semiacute infarction model
Florian Krackhardt1, Jonathan M Harnoss1,2, Matthias W Waliszewski1
1Department of Internal Medicine and Cardiology.
Insights
This study confirms pre-existing coronary anastomoses in a porcine model, offering a new preclinical approach for arteriogenetic research in ischemic heart disease patients.
Area of Science:
- Cardiovascular Research
- Medical Imaging
- Animal Models
Background:
- Severe ischemic heart disease often results in incomplete revascularization and persistent angina.
- Therapeutic arteriogenesis is a promising strategy for improving blood supply to ischemic myocardium.
- The origin of collateral formation in hypoperfused myocardium (angiogenetic vs. preformed anastomoses) is debated.
Purpose of the Study:
- Develop a reliable animal model for studying semiacute myocardial infarction with low mortality.
- Investigate whether collateral revascularization follows a pre-existing anatomical 'blueprint'.
Main Methods:
- Utilized a porcine model with stepwise occlusion of the left anterior descending artery via stent implantation.
- Performed serial coronary angiography and cardiac MRI for in vivo monitoring of vessel occlusion and collateral development up to 56 days.
- Evaluated collateral growth post-mortem using microcomputer tomography.
Main Results:
- Confirmed the existence of preformed coronary anastomoses (natural bypasses) in the porcine model.
- Demonstrated proliferation of functional vessels in hypoperfused myocardium.
- Cardiac MRI revealed the functional impact of developing collaterals.
Conclusions:
- Preformed coronary anastomoses play a role in collateralization of hypoperfused myocardium.
- This finding provides a preclinical basis for developing arteriogenetic therapies for ischemic heart disease.
- The study validates a novel animal model for investigating therapeutic arteriogenesis.
Background:
For patients with severe ischemic heart disease, complete revascularization by a percutaneous coronary intervention or coronary artery bypass grafting is often not achieved and may still cause residual angina. In case of progressive coronary artery occlusions, therapeutic arteriogenesis constitutes a promising strategy for increasing blood supply to the ischemic myocardium. Whether the formation of collaterals in the hypofused myocardium is angiogenetic in nature or based on preformed coronary artery anastomoses remains debatable. The objectives of this research were (i) the development of an appropriate research methodology to study a humanoid animal semiacute infarction model with low mortality and (ii) to answer the question of whether collateral revascularization follows a pre-existing 'blueprint'.
Materials And Methods:
A porcine model was chosen in which a step-wise vessel occlusion was performed by implantation of a copper stent into the distal left anterior descending artery. Vessel occlusion and collateral development were confirmed in vivo every 14 days up to day 56 by repeated coronary angiography and myocardial perfusion measurement using cardiac MRI. After the completion of the in-vivo imaging studies, animals were euthanized and collateral growth was evaluated using microcomputer tomography.
Results:
Our porcine model of semiacute noninvasive coronary artery occlusion confirmed the existence of preformed coronary anastomoses and the proliferation of functional vessels in hypoperfused myocardium. Repetitive intra-animal MRIs showed the functional impact of these growing collaterals.
Conclusion:
The confirmation of preformed coronary anastomoses during the process of collateralization (natural bypasses) offers a preclinical avenue to carry out arteriogenetic pharmaceutical research in patients with ischemic heart disease.
