The performance of ice-free cryopreserved heart valve allografts in an orthotopic pulmonary sheep model.
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.
Lisy
Milan
M
Dept. Thoracic, Cardiac and Vascular Surgery, University Hospital Tuebingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany.
Pennecke
Juliane
J
Brockbank
Kelvin G M
KG
Fritze
Olaf
O
Schleicher
Martina
M
Schenke-Layland
Katja
K
Kaulitz
Renate
R
Riemann
Iris
I
Weber
Corinna N
CN
Braun
Josephine
J
Mueller
Kerstin E
KE
Fend
Falko
F
Scheunert
Torsten
T
Gruber
Achim D
AD
Albes
Johannes M
JM
Huber
Agnes J
AJ
Stock
Ulrich A
UA
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
D007053:Ice