Bioprosthetic cardiac valve degeneration: role of inflammatory and immune reactions.

: Inflammatory and immune reactions are thought to mediate both calcification and biodegradation of bioprosthetic cardiac valve implants. To investigate the mechanisms of implant degeneration, we evaluated the role of inflammatory and immune reactions and the effects of tissue preservative treatment in three series of experiments. In the first experiment, three kinds of implants, i.e. glutaraldehyde-treated autograft Sprague-Dawley (SD) rat skin, xenograft Swiss-Webster (SW) mouse skin, and saline-treated autograft (control) were subcutaneously implanted in ten weanling SD rats, and retrieved after 70 days. There was no significant difference in the level of calcification in the autograft (113.13 +/- 27.09 micrograms/mg dry weight) and xenograft (78.27 +/- 31.53 micrograms/mg dry weight) (p > 0.05), but both differed significantly from the control specimens (1.55 +/- 0.87 micrograms/mg dry weight). In the second experiment, the immunological response to glutaraldehyde-treated bovine pericardium (glut tBP) and glycerol treated bovine pericardium (glyc tBP) implants were tested in vivo and in vitro. A Gore-Tex implant was used as a control. Sections of these materials were implanted to the abdominal muscle wall of Lewis rats, with each group composed of twelve animals. Lymphocytes and sera from the animals were isolated, and histological examination was performed at two or four weeks post-implantation. Collagen type 1 (calf skin) was used as antigen. Tritiated thymidine incorporation was used to measure lymphocyte response to antigen collagen type 1 (calf skin), and an Enzyme Linked Immunosorbent Assay (ELISA) was used to test antibodies. The results showed that lymphocytes from both the glut tBP and the glyc tBP groups responded to collagen type 1. The ELISA results showed that the glyc tBP group produced more antibodies than did the glut tBP group, with the difference being significant at a level of p < 0.02. Histology revealed that the glyc tBP had greater inflammatory changes and collagen degeneration than did the glut tBP. In the third experiment, sections of glut tBP and glyc tBP were implanted subcutaneously in two groups of ten weanling SD rats, and retrieved after 70 days. The results showed that glut tBP caused more calcification (197.04 +/- 83.56 micrograms/mg dry weight) than did the glyc tBP (6.74 +/- 0.55 microgram/mg dry weight), with the difference being significant at a level of p < 0.05. From these investigations it is concluded that tissue treatment prior to implantation was very important in determining the tendency of tissue to calcify, and that there was no obvious relationship between bioprosthetic calcification and immunogenicity.