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Published on: July 29, 2020
Blood flow to the heart from noncoronary arteries: an intriguing but challenging research field
Marco Picichè1, Elie Fadel, John G Kingma
1Cardiac Surgery Department, San Bortolo Hospital Vicenza, Italy. marco.piciche@libero.it
Insights
This study explored enhancing noncoronary collateral blood flow in dogs using internal thoracic artery ligature and growth factors, but the complex protocol led to high mortality and inconclusive results for ischemic heart disease therapy.
Area of Science:
- Cardiovascular Research
- Surgical Innovation
- Ischemic Heart Disease
Background:
- Noncoronary collateral circulation can supply blood to the heart.
- Augmenting this network is a potential therapy for ischemic patients.
- Research in this area is challenging.
Purpose of the Study:
- To investigate enhancing noncoronary collateral blood flow.
- To test the combined approach of left internal thoracic artery ligature and angiogenic growth factors.
- To assess feasibility in a canine model.
Main Methods:
- Eight dogs underwent three surgical procedures.
- Coronary artery constriction was induced.
- Left internal thoracic artery was ligated and vascular endothelial growth factor was delivered via micro-pump.
- Blood flow was measured using neutron-activated microspheres.
Main Results:
- High mortality rate (50%) after initial surgery.
- Only one dog survived the full protocol.
- Coronary angiography and microsphere analysis showed no evidence of neovascularization or increased blood flow.
Conclusions:
- The experimental protocol was too demanding for the canine subjects.
- Despite technical challenges, noncoronary collateral blood flow remains a promising area for ischemic heart disease research.
- Further investigation is warranted to explore this therapeutic potential.
Introduction:
It has been proven that blood supply to the heart can include blood from noncoronary collateral circulation. Whether this network can somehow be augmented to provide an alternative therapy for ischemic patients is an intriguing hypothesis with no clear answer yet due to the challenging nature of this research field. In an attempt to enhance noncoronary collateral blood flow, we experimented with left internal thoracic artery ligature and angiogenic growth factors in a canine model.
Materials And Methods:
Eight dogs weighing between 20 and 29 kg were scheduled for three operations each. Neutron-activated microspheres were used for blood flow measurement throughout the study. The first operation was a left thoracotomy for ameroid constrictor positioning at the proximal segment of the circumflex coronary artery. Three weeks later the left internal thoracic artery was ligatured distally. A micro-pump was positioned in the mediastinum, connected with a small catheter inserted in the proximal segment of the left internal thoracic artery for slow delivery of vascular endothelial growth factor. The protocol called for a coronary angiography 4 weeks later, sacrifice of the animals, and explantation of the heart for microsphere analysis.
Results:
Four of the dogs failed to tolerate ameroid constrictor positioning by thoracotomy and died after the first operation. The remaining four dogs underwent a second operation to ligate their left internal thoracic arteries and implant micro-pumps with catheters. The implant was a success, but only one dog survived in the postoperative period. When the last dog was voluntarily sacrificed after a third operation, coronary angiography showed no neovascularization, nor did heart slice analysis reveal microspheres.
Conclusions:
Despite the technical challenge of building research protocols to exactly quantify blood from noncoronary arteries, there are many historical, anatomical, physiopathological, clinical, radiological, and surgical indications suggesting that blood flow from extracardiac structures may play an important role in ischemic heart disease. Our preliminary investigation combining internal thoracic artery occlusion and angiogenic growth factors was unsuccessful for several reasons, the main one being it was too heavy a protocol for the dogs. Despite this, we think that noncoronary collateral blood flow represents an intriguing research field worthy of debate and further study.
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