Activation of connective tissue cells in vital pericardium, relevance to the behavior of vital autologous pericardial implants in cardiovascular surgeries

The use of vital autologous pericardium as a cardiovascular repair biomaterial has produced mixed results. Autologous pericardium was found to behave favorably as a patch for left ventricle repair and atrial septal defect closure and as a conduit for pulmonary artery and right ventricular outflow-tract reconstruction. In contrast, fresh autologous pericardium became fibrotic when used for mitral valve chordae and leaflet repair. Our laboratory investigated healing reactions of vital autologous pericardium implanted as a flap in the descending aorta of sheep (a model that simulated a heart valve leaflet, Cheung et al., 1999). In this in vivo model the pericardium became fibrotic and was characterized by cellular accumulation and tissue retraction. Histological analysis of recovered implants indicated that activation of cells endogenous to the pericardium contributed to the detrimental healing outcome.; Here we report an in vitro model of pericardial tissue healing using living pericardium. In this in vitro model, pericardial tissue contracted and the cells in situ expressed the proliferative marker PCNA and procollagen. These physical and cellular changes of cultured pericardium were stimulated by blood serum in a dose dependent manner and could be modulated by chemical inhibition of protein synthesis and protein function. In these studies, serum-stimulated pericardial tissue contraction was dependent upon the synthesis and deposition of Type I collagen. The mechanism of tissue contraction through the deposition of collagen is unknown. In addition, serum-stimulated cellular proliferation was independent of both tissue contraction and collagen synthesis. These data suggest that fibrosis of vital autologous pericardium in vivo may occur in response to the activation of cells in situ to the implant. One mechanism of cellular activation was through the exposure to blood serum. Data acquired from this in vitro study indicated that the microenvironment associated with cells and tissues is unique to those tissues and changes in tissue microenvironment may result in cellular activation and possible detrimental healing reactions.