Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B,, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B,, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications. Key Words: Calcification-Fibrinogen-Vitamins-Cellular involvement.Cardiac valve disease is frequently treated by prosthetic heart valve replacement. Calcification has limited the durability of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardiums (1-3). The determinants of mineralization include factors related to both the host metabolism and the implant structure and chemistry. Schoen et al.(3) postulate that calcification in bioprosthetic heart valves probably result from the inability of valvular cells to compartmentalize their low calcium content relative to the extracellular environment. Unfortunately, the exact mechanism of induction and propagation of this drawback is not well defined, and thus the method to prevent the calcification is not yet clear.Basically 2 types of approaches have been tried to ~~~ reduce pericardial calcification. Implant modification to prevent calcification includes the use of pretreatment of implant surfaces with various agents like diphosphonate, sodium dodecyl sulfate (SDS), protamine sulfate, aluminum, ferric ions, 2-amino oleic acid, etc. (43) and the local polymeric delivery of some of these agents (6). Recently, we reported the in vitro and in vivo efficacy of prolonged release chitosan matrices containing protamine sulfate and fe...