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Thorac Cardiovasc Surg 2001; 49(2): 78-83
DOI: 10.1055/s-2001-11711
Original Cardiovascular
© Georg Thieme Verlag Stuttgart · New York

Primary Tissue Failure of Bioprostheses: New Evidence from In Vitro Tests[*]

M. Deiwick1 , B. Glasmacher3 , E. Pettenazzo4 , D. Hammel1 , W. Castellón2 , G. Thiene4 , H. Reul3 , E. Berendes5 , H. H. Scheld1
  • 1Klinik und Poliklinik für Thorax, Herz- und Gefäßchirurgie, Münster, Germany
  • 2Labor für Biophysik, Institut für Experimentelle Audiologie, Münster, Germany
  • 3Helmholtz-Institut für Biomedizinische Technik, Aachen, Germany
  • 4Department of Pathology, University of Padua, Italy
  • 5KIinik für Anästhesiologie und Operative Intensivmedizin, Münster, Germany
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Publication History

Publication Date:
31 December 2001 (online)

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Background: Primary tissue failure, which is mainly caused by calcification, is still the limiting factor in the long-term outcome of heart valve bioprostheses. Even though the precise nature of this process is not fully understood, in vitro tests have been developed to reproduce and predict calcification for individual bioprostheses. Methods: In vitro calcification testing was performed by using an accelerated pulsatile valve tester which was adapted for testing stented as well as stentless bioprostheses with physiological fluid dynamics. A total of 84 bioprostheses (porcine, pericardial and stentless porcine of different manufacturers) were cyclically loaded at a test rate of 300/min at 37° C within a rapid calcification fluid with CaxP = 130 (mg/dl)2 at pH 7.4. Calcification was assessed by microradiography after 12 × 106 cycles. In a previous step, holographic interferometry was performed to identify irregularities of valve leaflets in order to predict later calcification. Selected specimens of calcified bioprostheses underwent histology, transmission (TEM) and scanning (SEM) electron microscopy. Tissue mineralization was investigated by coupling SEM, electron microprobe analysis (EMPA) and X-ray powder diffraction (XRPD) methods. Results: For all tested bioprostheses, a significant calcification was achieved within 4 to 6 weeks of ongoing testing, and the degree of calcification increased with time. A significant correlation between calcification and leaflet irregularities (detected by holographic interferometry) was found (r = 0.80, p = 0.001). Calcification varied between individual bioprostheses, and significant differences were detected for different groups (calculated as percentage of total leaflet area, mean ± SD): porcine stented (37.3 ± 12.0 %), bovine stented (23.0 ± 8.9 %), porcine stentless (16.2 ± 7.6 %). Histological and ultrastructural investigation showed intrinsic calcification involving both the spongiosa and fibrosa with collagen fibrils, interfibrillar spaces and cells as early sites of calcification. There was clear evidence of apatite crystallization, and observations made with in vitro calcification were quite similar to those occurring with in vivo implanted bioprostheses. Conclusion: In vitro tests can reproduce intrinsic calcification of bioprostheses even in the absence of viable biologic host factors. Moreover, degree and sites of calcification have become predictable. This enables the development and evaluation of bioprostheses with reduction of animal experiments. From our results obtained with a broad range of available bioprostheses, stented bovine and stentless porcine valves seem to be superior to conventional stented porcine bioprostheses with regard to leaflet calcification.<

Key words:

Bioprostheses - Calcification - Hologram interferometry - Quality control - Pathology

1 Presented at the D-A-CH Congress, February 10 - 13, 2000, Lucerne, Switzerland

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1 Presented at the D-A-CH Congress, February 10 - 13, 2000, Lucerne, Switzerland

PD Dr. med. Michael Deiwick

Klinik und Poliklinik für Thorax-, Herz- und Gefäßchirurgie
Westfälische Wilhelms-Universität

Albert-Schweitzer-Straße 33

48129 Münster

Germany

Phone: ++49/251/ 834 7401

Fax: ++49/251 / 834 8316

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