Vitamin-B6 Pretreated Bovine Pericardial Bioprosthetic Heart Valve Leaflets Demonstrate Reduced Platelet Adhesion and Activation.

Abstract

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue such as glutaraldehyde fixed bovine pericardium (BP), while less thrombogenic than mechanical valve prostheses, nevertheless demonstrate a significant risk for platelet initiated thromboembolic events. We showed previously using in vitro and in vivo model systems that pyridoxamine (PYR), a Vitamin B6 vitamer, used as a BP pretreatment, mitigated advanced glycation end product (AGE) formation. PYR is also known to inhibit platelet aggregation. In the present studies, both BP and collagen-coated polyvinyl chloride tubing (PVC-collagen) were fixed with glutaraldehyde and were either untreated or pretreated with PYR; both the PYR content and binding stability were quantitated. PYR-BP binding stability was demonstrated in vitro over 28 days. Methylglyoxal (MGO), a representative AGE, was used to modify BP and PVC-collagen for use in platelet activation studies in an ex vivo flow loop with human whole blood. MGO modified collagen-coated PVC demonstrated both increased platelet activation, per P-selectin expression, and increased platelet adhesion compared to non-MGO modified samples. PYR pretreatment of either collagen-coated PVC or BP, with or without MGO exposure, significantly mitigated these effects. In conclusion, BP and collagen surfaces are susceptible to platelet activation and adhesion that is effectively mitigated by vitamin B6.