The aim of this project is to find a safer, simpler and cheaper preservation method for cardiac valve allografts. This requires the answer to two specific questions:-
Are living cells required in a tissue valve at the time of implantation?
Can the safety of tissue valves be improved by more aggressive antimicrobial treatment without reducing their effectiveness as grafts?
Replacement of valves is now a standard surgical procedure. Mechanical and bioprosthetic valves are most commonly employed but in certain situations tissue allografts are preferred - in children, in women of child-bearing age and in the presence of endocarditis. For obvious practical reasons some method of preservation of the valve during the time between procurement and implantation is essential. This proposal seeks to address two urgent and interrelated questions: Is it necessary to maintain viable cells in the tissue graft? What steps can be taken to reduce the risk of transmission of diseases, especially viral diseases, via human tissue grafts? The questions are interrelated because disinfection methods that allow tissue cells to survive are imperfect against bacteria and ineffective against viruses: if cellular viability were unnecessary, then much more reliable sterilisation methods would be available. Current practice assumes that cellular viability is required, but the supporting evidence for this view is poor. Three methods of processing and storing valves, plus freshly isolated control valves, will be studied. Valves cryopreserved with dimethyl sulphoxide contain living cells but this method does not permit aggressive disinfection. Valves that have been snap frozen without cryoprotectant contain few if any living cells and can therefore be subjected to aggressive antimicrobial treatment. However, ice forms within the tissue and this may reduce their durability. Valves that have been vitrified with 2,3-butanediol do not contain living cells either and can therefore receive aggressive disinfection, and since no ice is formed they are expected to be more durable. The most effective preservation methods will be defined in sheep. Valves that have been deliberately contaminated with bacteria and viruses will be subjected to a range of physical and chemical antimicrobial treatments and then tested for sterility, the survival of living cells, and morphological damage. The most effective disinfection methods will then be combined with preservation and in vitro and in vivo studies carried out.
Funding SchemeCSC - Cost-sharing contracts
2795 Carnaxide Oeiras
3508 TD Utrecht