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A calcified chronic total occlusion preclinical model
Azriel B Osherov1,2, Beiping Qiang1, Jagdish Butany3,4
1Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Summary
This study developed a calcified chronic total occlusion (CTO) model in rabbits using diet and local injections. The model successfully created calcified CTOs, crucial for testing new treatments for heavily calcified artery blockages.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Preclinical Models
Background:
- Percutaneous revascularization of chronic total occlusions (CTOs) often fails in cases of severe calcification.
- A reliable preclinical model of calcified CTO is essential for developing novel treatment strategies.
Purpose of the Study:
- To establish an experimental model of chronic total occlusion (CTO) with significant calcification.
- To achieve calcification through dietary modifications and local pro-calcification factor injections.
Main Methods:
- Chronic total occlusions (CTOs) were induced in rabbit femoral arteries using a thrombin injection model.
- Dietary interventions included high cholesterol, calcium carbonate, and vitamin D supplementation.
- Local injections of bone morphogenetic protein-2 (BMP-2), dipotassium phosphate, and calcium chloride were administered in select animals.
Main Results:
- CTOs exhibited chronic inflammation and fibrosis.
- Mineralization (calcification/ossification) was observed in 78% of arteries with calcium/vitamin D supplementation, appearing as early as 2 weeks.
- Mineralization occurred in 85% of BMP-2 treated arteries and 60% of non-BMP-2 treated arteries.
Conclusions:
- Dietary supplementation with calcium and vitamin D, alongside cholesterol, effectively induces complex mineralization in preclinical CTO models.
- This model provides a valuable platform for evaluating new approaches to treat calcified CTOs.
