Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts

Glutaraldehyde-treated porcine aortic valve xenografts frequently fail due to calcification. Calcification in the prostheses begins Intracellularly, I n a previous study, various types of cell injury to canine valvular fibrobl asts, including glutaraldehyde treatment, led to calcification, An Influx o f extracellular Ca2+ into the phosphate-rich cytosol was theorized to be th e mechanism of calcification. To test the Ca2+ influx theory, cytosolic Ca2 + and P-i concentrations were assessed in glutalaldehyde-treated porcine ao rtic valve fibroblasts, and their relationship to a subsequent calcificatio n was studied. Glutaraldehyde caused an immediate and sustained massive cyt osolic Ca2+ increase that was dose dependent and a severalfold increase in P-i. Calcification of cells followed within a week. The earliest calcificat ion was observed in blebs formed on glutaraldehyde-treated cells. Live cont rol cells or cells fixed with glutaraldehyde in Ca2+-free solution did not calcify under the same conditions. Concomitant increases In Ca2+ and P-i In glutaraldehyde-ttreated cells appear to underlie the mechanism of calcific ation, and the presence of extracellular Ca2+ during glutaraldehyde fixatio n promotes calcification.