COMPLEMENT ACTIVATION IS INVOLVED IN THE STRUCTURAL DETERIORATION OF BOVINE PERICARDIAL BIOPROSTHETIC HEART-VALVES

Disintegrated collagen fibers surrounded with protein deposits are a m orphologic feature in torn, folded, and disrupted cusps of pericardial prostheses explanted for clinical dysfunction. New technologies for v alve bioprostheses with improved durability require further investigat ion of molecular mechanisms initiating the deterioration of bioprosthe tic valves. The authors' aim was to obtain experimental evidence of bi ologic factors contributing to the degradation of the bioprosthetic ma trix. Clinically failed Mitroflow (22), Hancock (3), Ionescu-Shiley (2 ), and Sorin (1) valves were explanted after 69-170 months. Non calcif ic deterioration of the prosthetic matrix was studied with labeled ant ibodies to plasma proteins and cells. IgG, and complement proteins C1q , C3, and C4 were accumulated close to dissociated collagen bundles (2 6/28) throughout the prostheses. Fibrin was identified on the cuspal s urface and in the deep disrupted areas. The fibrin peptides and proteo lytic breakdown products of the complement components, the latter cons istent with complement activation and chemotaxis for monocytes, were s hown by immunoenzymic assay on Western blots from the valve extracts. The complement activation triggered by the IgG aggregates generates bi oactive peptide signals that can activate macrophages (22/28) and neut rophil granulocyte elastase (22/24) able to cooperate with the mechani cal stress in the breakdown of the chemically processed, non hemocompa tible, and non-self macromolecular matrix.