title: The performance of ice-free cryopreserved heart valve allografts in an orthotopic pulmonary sheep model.
abstract: Transplantation of cryopreserved heart valves (allografts) is limited by immune responses, inflammation, subsequent structural deterioration and an expensive infrastructure. In previous studies we demonstrated that conventional frozen cryopreservation (FC) is accompanied by serious alterations of extracellular matrix (ECM) structures. As the main culprit of the observed damages ice crystal formation was identified. Objective of this study was the application principles of cryoprotection as observed in nature, occurring in animals or plants, for ice-free cryopreservation (IFC) of heart valves. Using IFC, valves were processed and stored above the glass transition temperature of the cryoprotectant formulation (-124 degrees C) at -80 degrees C to avoid any ice formation, tissue-glass cracking and preserving ECM. After implantation in the orthotopic pulmonary position in sheep, we demonstrate that IFC resulted in cell free matrices, while maintaining crucial ECM-components such as elastin and collagen, translating into superior hemodynamics. In contrast, we reveal that FC valves showed ECM damage that was not restored in vivo, and T-cell inflammation of the stroma with significant leaflet thickening. Compared to currently applied FC practice IFC also reduced infrastructural needs for preservation, storage and shipping. These results have important implications for clinical valve transplantation including the promise of better long-term function and lower costs.
authors.affiliation: Dept. Thoracic, Cardiac and Vascular Surgery, University Hospital Tuebingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany.
authors.forename: Milan
authors.initials: M
authors.lastname: Lisy
authors.forename: Juliane
authors.initials: J
authors.lastname: Pennecke
authors.forename: Kelvin G M
authors.initials: KG
authors.lastname: Brockbank
authors.forename: Olaf
authors.initials: O
authors.lastname: Fritze
authors.forename: Martina
authors.initials: M
authors.lastname: Schleicher
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
authors.forename: Renate
authors.initials: R
authors.lastname: Kaulitz
authors.forename: Iris
authors.initials: I
authors.lastname: Riemann
authors.forename: Corinna N
authors.initials: CN
authors.lastname: Weber
authors.forename: Josephine
authors.initials: J
authors.lastname: Braun
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Mueller
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Torsten
authors.initials: T
authors.lastname: Scheunert
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Albes
authors.forename: Agnes J
authors.initials: AJ
authors.lastname: Huber
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Stock
mesh_terms: D000818:Animals; D015925:Cryopreservation / Q000379:methods*; D003952:Diagnostic Imaging; D005260:Female; D005453:Fluorescence; D019918:Heart Valve Prosthesis Implantation; D006351:Heart Valves / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D007053:Ice; D008168:Lung / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D017785:Photons; D012756:Sheep; D019265:Spectroscopy, Near-Infrared; D014184:Transplantation, Homologous
chemical_list: D007053:Ice