BACKGROUND: The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues. However, the effectiveness of antimineralization treatment can be overestimated in subcutaneous implants, since specimens using this model are not subjected to mechanical and dynamic stress or blood-surface contact. The purpose of this study was to evaluate the influence of blood contact on the calcification of bioprosthetic valves. METHODS: Glutaraldehyde-pretreated porcine aortic valves were prepared. Aortic wall and cusp discs were implanted subcutaneously in six rats for 8 weeks and were implanted within the jugular vein wall in six sheep for 3 and 6 months (blood contact model). Tissue discs were analyzed by gross inspection, radiography and light microscopy. Calcium content was determined by atomic absorption spectrometry. RESULTS: X-ray and light microscopic examination showed calcification in the cusps to be higher than that in the aortic wall in the rat subcutaneous model. On the other hand, in the blood contact model, the cusps were slightly calcified and calcification in the aortic wall was more pronounced. Calcium analysis in rats revealed more calcium in the cusp than in the aortic wall (71.5+/-9.7 g/mg dry tissue vs. 53.7+/-2.6, p=0.09). Tests for calcium content of the jugular vein samples in sheep showed significantly more calcium in the aortic wall than in the cusp (3 months, 7.9+/-1.5 vs. 0.3+/-0.1, p<0.0001; 6 months, 77.2+/-6.1 vs. 27.2+/-10.2, p=0.0002). In addition, aortic wall and cusp calcification significantly increased with time. CONCLUSIONS: These data suggest that the results from the rat subcutaneous model were completely opposite to those for the blood contact model. This study confirms the need to include blood contact as a factor in in vivo pre-clinical valve testing.
BACKGROUND: The rat subcutaneous model reproduces clinically observed mineralization of bioprosthetic tissues. However, the effectiveness of antimineralization treatment can be overestimated in subcutaneous implants, since specimens using this model are not subjected to mechanical and dynamic stress or blood-surface contact. The purpose of this study was to evaluate the influence of blood contact on the calcification of bioprosthetic valves. METHODS:Glutaraldehyde-pretreated porcine aortic valves were prepared. Aortic wall and cusp discs were implanted subcutaneously in six rats for 8 weeks and were implanted within the jugular vein wall in six sheep for 3 and 6 months (blood contact model). Tissue discs were analyzed by gross inspection, radiography and light microscopy. Calcium content was determined by atomic absorption spectrometry. RESULTS: X-ray and light microscopic examination showed calcification in the cusps to be higher than that in the aortic wall in the rat subcutaneous model. On the other hand, in the blood contact model, the cusps were slightly calcified and calcification in the aortic wall was more pronounced. Calcium analysis in rats revealed more calcium in the cusp than in the aortic wall (71.5+/-9.7 g/mg dry tissue vs. 53.7+/-2.6, p=0.09). Tests for calcium content of the jugular vein samples in sheep showed significantly more calcium in the aortic wall than in the cusp (3 months, 7.9+/-1.5 vs. 0.3+/-0.1, p<0.0001; 6 months, 77.2+/-6.1 vs. 27.2+/-10.2, p=0.0002). In addition, aortic wall and cusp calcification significantly increased with time. CONCLUSIONS: These data suggest that the results from the rat subcutaneous model were completely opposite to those for the blood contact model. This study confirms the need to include blood contact as a factor in in vivo pre-clinical valve testing.