Glutaraldehyde Treated Bovine Pericardium: Changes in Calcification Due to Vitamins and Platelet Inhibitors

Abstract

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...

Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative

“…Thus, the extraction of cellular components from BP tissues should minimize immunologically induced inflammatory processes and attenuate the calcification occurring as a late sequela of inflammatory [21,22]. Table 1 Calcium content, phosphorous content and Ca/P (molar ratio) of the different groups implanted 4 weeks, 6 The significant differences were found between the GFaBP group and the GFaBP-HA group after four, six and eight-week implantations. In fact, the calcium contents of GFaBP-HA group were about 10 times lower than those of the GFBP group after eight-week implantations (0.25±0.08 comparing to 2.44±0.55 ȝgCa/mg).…”

“…Despite the clinical importance of the problem, the pathogenesis of calcification is incompletely understood. According to present studies, there are several currently accepted reasons resulting in calcification: (i) immunogenicity resulted from cells, cellular components and soluble proteins of xenogenic tissue may be the major factor contributing to the calcification [1]; (ii) lipid-based cell debris, in particular the acid phospholipids of cell membranes could serve as the initial nuclei of calcification [2]; (iii) incomplete glutaraldehyde binding to collagen also yields cytotoxic aldehyde group residuals including loosely bound glutaraldehyde and unreacted aldehyde groups, which could also induce calcification [3,4]; (iv) voids and cavities in the tissue, which were created by the removal of cellular components and proteoglycans during processing, cellular degradation, or chemical treatment, afford a potential space for calcium phosphate depositing [5]; and (v) certain medicines such as steroid hormones, antibiotic drugs, vitamins, antiplatelet drugs, anticoagulants, etc., can alter protein surface attachment and modulate the calcium transport and subsequent tissue calcification [6,7].…”

Bovine pericardium retail preserved in glutaraldehyde and used as a vascular patch

“…According to Schoen et al [7,8], Chanda et al [21], Vasudev et al [22] and Pires et al [9] this calcification is a multifactorial phenomenon, but it is not well defined and varies in different animal models. The authors pointed out that calcification in bovine pericardium used as a vascular patch presented a different connotation of calcification than valvular prostheses, because it implied a reduction in leaflet mobility, resulting in dysfunction of the prosthesis, which was not observed in vascular grafts.…”

Cardiovascular calcification and bone: a comparison of the effects of dietary and serum antioxidants

“…where vitamin C intake in postmenopausal women was stratified by calcium intake, it was found that all the increase in BMd was clustered among those with calcium intake >500mg/d while there was no association between vitamin C intake and BMd where calcium intake was lower 58 . leveille et al found that food-derived vitamin C was not associated with BMd in postmenopausal women but supplements for women aged [55][56][57][58][59][60][61][62][63][64] , but not older, used for ≥10 years showed a significantly higher BMD 68 .…”

“…ascorbic acid may, often together with alpha-tocopherol, lower induced calcification in VSMCs 14,[60][61][62] , possibly by reducing transport of calcium ions 61 . In observational studies, however, intake of vitamin C was not associated with the CaC score in asymptomatic subjects 34 , while dietary and plasma vitamin C showed no association with cIMt or carotid plaque 35 .…”