Abstract 16373: Pyridoxamine (Vitamin B6) Mitigation of Protein Glycation and Deleterious Platelet-Material Interactions in Bioprosthetic Heart Valve Leaflets

Introduction: Though bioprosthetic heart valves (BHV) most often do not require anticoagulation, it has been reported that 12% of BHVs have significant leaflet thrombosis. We identified Vitamin B6 (pyridoxamine, abbr. PYR) as a pretreatment agent to reduce advanced glycation end-product (AGE) accumulation within bovine pericardial (BP) BHVs. AGEs contribute to valvular degeneration through collagen crosslinking and immune signaling. PYR is also known to inhibit platelet aggregation.

Hypothesis: PYR pretreatment and supplementation mitigate BHV thrombosis.

Methods: Glutaraldehyde fixed collagen coated (GFC) PVC tubing was used as a leaflet surface model and methylglyoxal (MGO) pretreatment to simulate glycation. PYR pretreated collagen surfaces and perfusate PYR supplementation were compared to untreated controls. These studies were repeated with glycated GFC. Fresh citrated human whole blood from healthy donors was perfused over the surfaces for 4 hours at 37 °C and arterial shear using the Chandler loop apparatus. Post perfusion platelet activation (CD62P expression via flow cytometry) and nitric oxide synthase (NOS) activity were measured. Platelets adhered to the tubing sections were visualized and quantitated via scanning electron microscopy.

Results: PYR pretreatment of GFC surfaces reduced platelet activation after perfusion compared to the control (Fig1a). Surface glycation with MGO resulted in increased platelet activation, but PYR pretreatment of the glycated surface mitigated the effect of glycation on platelet activation (Fig1b). NOS activity was impaired by surface glycation and PYR treatment appears to rescue function in glycated environments (Fig1c). Platelet adhesion to GFC was increased by glycation (Fig1d-f).

Conclusions: Glycated surfaces, even in euglycemia, are prothrombotic when compared to non-glycated surfaces. Vitamin B6 reduces platelet activation and adhesion in both glycated and non-glycated environments.