The association of bound aldehyde content with bioprosthetic tissue calcification.

The rapid progression of mineralization seen in glutaraldehyde-treated valves has prompted a wide variety of secondary treatments aimed at mitigating dystrophic calcification. We tested the hypothesis that aldehyde residuals bound to bioprosthetic tissue is a significant promoter of calcification. We developed a novel assay to measure residual aldehyde functional groups and assessed aldehyde content in three different groups: glutaraldehyde-fixed tissue (Glut-only), Edwards ThermaFix™ treated tissue and Edwards RESILIA™ tissue. The amount of tissue calcification in these same groups was assessed in vivo using a well-established rabbit model, in which tissue samples were implanted intramuscularly for 60 days. The aldehyde content of the Glut-only, ThermaFix™ treated and RESILIA™ tissues were 225.7 ± 31.5, 101.9 ± 79.7 and 32.5 ± 48.4 nmol/g, respectively. The differences among all three groups were highly significant (p < 0.001, Student's unpaired t test). The median (interquartile range) calcium content of the Glut-only, ThermaFix™ treated and RESILIA™ tissues were 227.4 (221.8-243.6), 101.0 (23.05-169.6), and 10.1 (0.28-51.7) µg/mg. The differences among all three groups were highly significant (p < 0.001, Mann-Whitney U test). The results indicated that our novel assay was able to reliably measure aldehyde content in bovine pericardial tissue. Furthermore, there appeared to be a close association between aldehyde content and tissue calcium content. The processing of bioprosthetic valves to reduce their aldehyde content may offer a significant advantage in terms of reducing the potential for long-term calcification in human implants.

Influence of Tissue Technology on Pannus Formation on Bioprosthetic Heart Valves.

PURPOSE: Bioprosthetic heart valves have several modes of failure. Tissue degeneration and calcification are the major modes of failure with the highest focus of attention, however pannus formation can also be problematic. We studied the effect of a new tissue technology with the absence of any glutaraldehyde-based storage solution and a stable aldehyde capping process on pannus formation. METHODS: Using a juvenile sheep model of mitral valve replacement, valves with the new tissue technology were compared to control valves with contemporary bovine pericardial tissue, regarding pannus formation. Valves were implanted for either a 5- or 8-month period. Explanted valves were examined macroscopically and histologically. Histological observations were made by an independent pathologist, blinded to group identity. RESULTS: Pannus area measured macroscopically on the test valves was significantly lower than the pannus on the control tissue. This was confirmed on the histological samples, where the total pannus overgrowth was significantly lower in the test group compared to the control. CONCLUSION: The new tissue technology leads to less pannus formation. This may beneficially influence both short- and long-term valve behavior of bioprosthetic valves.

The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.

AIMS: To test whether the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand rosiglitazone (Ro) has therapeutic activity in the IL-10(-/-) mouse model of inflammatory bowel disease (IBD), and to identify the cellular targets and molecular mechanisms of Ro action. METHODS: The progression of spontaneous chronic colitis in IL-10(-/-) mice was compared in 5-week-old mice fed a standard diet with or without Ro for 12 weeks. The possible therapeutic effect of Ro was also tested over a 6-week interval in older IL-10(-/-) mice with established IBD. RESULTS: Treatment with Ro slowed the onset of spontaneous IBD in IL-10(-/-) mice. Crypt hyperplasia, caused by increased mitotic activity of crypt epithelial cells, was also delayed by Ro. Treatment with Ro significantly decreased expression of interferon gamma (IFNgamma), interleukin 17 (IL-17), tumor necrosis factor alpha, and the inducible nitric oxide synthase mRNA in the colon, whereas expression of IL-12p40 was unchanged. PPARgamma was detected in epithelial cells throughout the crypts and surface. Ro increased expression of PPARgamma protein in these cells, suggesting the existence of a positive feedback loop that would potentiate its action in these cells. Ro also specifically increased expression of a novel PPAR target, aquaporin-8 (AQP8), in differentiated colonic epithelial surface cells, demonstrating that PPARgamma is not only present but also regulates gene expression in these cells in vivo. Finally, Ro was ineffective in improving disease activity in older IL-10(-/-) mice with established IBD. CONCLUSIONS: PPARgamma is expressed, and the PPARgamma ligand Ro regulates gene expression in colonic epithelial cells. As a single agent, Ro works best for disease prevention in the IL-10(-/-) mouse model for IBD.