Antagonizing interleukine-8 improves the durability of biological aortic valves: Translation of fundamental results using a model of subcutaneous aortic valve implantation in rats into clinical application such as cardiac surgery
Résumé
Introduction
Aortic valvle stenosis is a common disease, only surgical therapy is recommended.
Objective
Using the model of subcutaneous aortic valve implantation in rats described first time by Fishbein et al. in 1982, we test the hypothesis that antagonizing Interleukine-8 (IL-8) receptors reduces calcification of the pig aortic valves.
Method
Pigs Hearts were explanted directly from the slaughter house. Aortic valvular leaflets were then implanted subcutaneously within 4 hours on the back of Sprague Dawley young rats. Every day for a total period of 14 days, rats received either local subcutaneous injection either intra-peritoneal injection of drug, either none drug. The drug was SCH527123, which is an antagonist of CXCR-1 and CXCR-2, receptors of IL-8. The 3 groups were sacrificed at the end of 14 days after a blood sampling and the aortic valvular leaflets were explanted to be analyzed. The analysis consisted of immuno-histochemistry coloration, calcium dosage and western-blot analysis.
Results
GA increases calcification. Inflammation is present highly concomitant with calcification. Macroscopical findings confirm the part of red blood cells in the mechanism of calcification.
Conclusion
Parallel with clinical results can be made as the age of patient.
The use of antagonist of CXCR-1 or CXCR-2 in the treatment of pre-incubation of bioprosthesis or oral prescriptions concomitant of the aortic valve replacement may be a lead for improving the durability of aortic bioprosthesis.