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Synergistic effect of released aspirin/heparin for preventing bovine pericardial calcification
S C Vasudev1, T Chandy, C P Sharma
1Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, India.
Insights
This study shows that combining aspirin and heparin in a novel drug-releasing matrix effectively inhibits calcification in bioprosthetic heart valves. This approach offers a promising strategy to improve the longevity and performance of these crucial medical devices.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Drug Delivery Systems
Background:
- Bioprosthetic heart valve calcification, often stemming from glutaraldehyde-treated bovine pericardium (GATBP), is a primary cause of clinical failure.
- Aspirin (antiplatelet) and heparin (anticoagulant) are standard treatments for post-implantation complications like thrombosis and thromboembolism.
Purpose of the Study:
- To investigate the efficacy of aspirin and heparin, delivered via a prolonged-release co-matrix, in preventing bioprosthetic calcification.
- To evaluate the synergistic effect of aspirin and heparin on inhibiting calcification in glutaraldehyde-treated bovine pericardium (GATBP).
Main Methods:
- Aspirin and heparin were embedded into a chitosan/polyethylene vinylacetate co-matrix for sustained release.
- In vitro and in vivo models were employed to assess the anti-calcification effects.
- Subcutaneous co-implantation of PEG-20,000 grafted bovine pericardium (PEG-GABP) with aspirin and heparin was performed.
Main Results:
- In vitro and in vivo studies indicated a synergistic effect of released aspirin/heparin in inhibiting GATBP calcification.
- Biochemical, histological, and scanning electron microscopy analyses of retrieved PEG-GABP samples showed significantly reduced calcium deposition and alkaline phosphatase activity compared to GATBP.
- The combination of aspirin and heparin demonstrated a synergistic inhibition of pericardial calcification.
Conclusions:
- The sustained release of aspirin and heparin from a co-matrix effectively inhibits bioprosthetic pericardial calcification.
- This combination therapy offers a dual benefit of anti-calcification and antithrombotic effects, potentially enhancing bioprosthetic heart valve durability.
- Further research into this synergistic approach could lead to improved long-term outcomes for patients with bioprosthetic heart valves.
Abstract:
Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). Aspirin, a potent antiplatelet drug, and heparin, an anticoagulant, are commonly used for postimplant complications such as thrombosis and thromboembolism. Aspirin and heparin were embedded in chitosan/polyethylene vinylacetate co-matrix to develop a prolonged release form. The effect of these drugs towards the bioprosthetic calcification was investigated by in vitro and in vivo models. In vitro and in vivo evaluation suggest that the released aspirin/heparin from the co-matrix had a synergistic effect in inhibiting GATBP calcification. In vivo subcutaneous co-implantation was performed with PEG-20,000 grafted bovine pericardium (PEG-GABP), aspirin, and heparin. Biochemical, histological, and scanning electron microscopic evaluation of retrieved samples demonstrated a significant reduction in calcium deposition and alkaline phosphatase activity on PEG-GABP compared to GATBP. It seems that the aspirin/heparin combination synergistically inhibits the pericardial calcification in addition to their antithrombotic function.