The Anticalcific Effect of Glutaraldehyde Detoxification on Bioprosthetic Aortic Wall Tissue in the Sheep Model

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Abstract
Background: Increasing concentrations of glutaraldehyde (GA) lead to a decreased rather than increased calcification of bioprosthetic aortic wall tissue. This study determined to what extent the benefit of better cross‐linking is masked by the intrinsic propensity of GA towards calcification. Materials and Methods: Porcine aortic roots were immediately fixed at the abattoir at three different concentrations of GA (0.2%, 1.0%, and 3.0% for 1 week at 4°C). Subsequently, roots underwent a GA extraction process using high volumes of Urazole solution (acetic acid buffer, pH 4.5, 37°C, 1 week) followed by NaBH4 reduction (2 days, 37°C). Roots were implanted in the distal aortic arch of young sheep for 6 weeks and 6 months. Calcium analysis was quantitatively done by atomic absorption spectrophotometry and qualitatively assessed by light microscopy on Von Kossa stains. Results: There was a distinct anticalcification effect of GA detoxification after 6 weeks (56.8% to 97.9%; 95% confidence interval [CI]), which stabilized on a more moderate level after 6 months of implantation (19.1% to 31.6%; 95% CI). The most pronounced effect of GA extraction was seen in 0.2% fixed tissue, where aortic wall calcification was mitigated by 97% and 32% after 6 weeks and 6 months, respectively. Mitigation of aortic wall calcification was 71% (6 weeks) and 21% (6 months) in the 3.0% GA group. The combined effect of higher cross‐link density and detoxification achieved an 82% (6 weeks) and 48% (6 months) reduction of calcium levels in the 3.0% GA group. In long‐term implants (6 months), detoxification alone on top of standard 0.2% GA fixation was as effective (from 174.1 ± 11.9 μg/mg without detoxification to 119.3 ± 19.3 μg/mg with detoxification) as 3.0% fixation (114.8 ± 10.0 μg/mg without detoxification to 91.3 ± 11.5 μg/mg with detoxification). Conclusion: We were able to determine in the circulatory sheep model to what degree the intrinsic procalcific effect of GA counteracts the protective effect of higher cross‐link density. Our study also established that the effect of detoxification is particularly pronounced in commercial low‐grade fixation.