Jean-Marie Girardot

Calcification of porcine valves: A successful new method of antimineralization☆☆☆

Despite distinct advantages over mechanical cardiac valve prostheses, the use of bioprosthetic valves remains limited due to poor long-term durability, primarily as a result of tissue calcification. A novel anticalcification process, based on treatment of porcine bioprostheses with a derivative of oleic acid, has been developed by one of us (J.M.G.) (US Patent Number 4,976,733). This process employing 2-aminooleic acid (AOA) was tested in a juvenile sheep model. Terminal studies after a 20-week interval included hemodynamic, radiographic, morphologic, and quantitative tissue calcium analyses. All control valves (n = 4) had thickened, immobile, heavily calcified leaflets, whereas all AOA-treated valves (n = 8) were pliable and free of calcium deposits. Calculated valve orifice areas for controls (0.9 +/- 0.2 cm2) (mean +/- standard error of the mean) was less than for AOA-treated valves (2.0 +/- 0.3 cm2) (p less than 0.05). Radiographic calcification scores were greatly elevated in the control (25.5 +/- 5.6) versus AOA-treated valves (0.5 +/- 0.5) (p less than 0.002). In quantitative mineralization studies, the mean calcium content of the control leaflets was 129 +/- 21 milligrams per gram dry weight cusp tissue versus 7.7 +/- 5.8 mg/g for AOA-treated valves (p less than 0.001). Pathologic examination confirmed heavy calcification in the control leaflets, which was essentially absent in the AOA-treated leaflets. However, cuspal hematomas in areas of structural loosening and surface roughening were noted in AOA-treated valves. This anticalcification process dramatically reduced mineralization of porcine valve prostheses in this model.

Refinement of the Alpha Aminooleic Acid Bioprosthetic Valve Anticalcification Technique

BACKGROUND Aminooleic acid treatment has been demonstrated to prevent porcine valve calcification and to protect valvular hemodynamic function. Initial enthusiasm was tempered by histologic studies of these AOA valves, which showed cuspal hematomas, structural loosening, and surface roughening. This prompted a systematic review of the AOA treatment process. Unsolubilized particles of alpha aminooleic acid present in the treatment solution were identified as the cause of mechanical abrasion of valve cusps during processing. These particles were eliminated with a revamped protocol, which included filtration of the AOA solution before valve preparation. METHODS Porcine aortic valve cusps treated with this modified AOA protocol (AOA II) were studied in a rat subdermal implant model of mineralization. A juvenile sheep trial was then used to confirm the antimineralization effects of AOA II on glutaraldehyde-fixed porcine aortic roots in a circulatory model of accelerated calcification. RESULTS Retrieved AOA II-treated cusps from the subdermal model were markedly less calcified than control cusps (AOA II, 1 +/- 0, 17 +/- 4, 23 +/- 6, and 17 +/- 10 versus control, 189 +/- 14, 251 +/- 16, 250 +/- 14, and 265 +/- 10 mg calcium/mg sample at 4, 8, 12, and 16 weeks, respectively; p < 0.0001). Morphologic examination of the AOA II cusps of the valves retrieved from the sheep demonstrated freedom from the structural loosening, surface roughening, and hematoma formation that had limited the utility of the original AOA preparation technique. Cusps from AOA II-treated porcine roots had significantly less calcium than control cusps (AOA II, 5.5 +/- 3.0 mg/g; control, 91.2 +/- 19.5 mg/g; p = 0.0004). The aortic walls had similar levels of calcification (AOA II, 156 +/- 73 mg/g; control, 159 +/- 10 mg/g; p = not significant). CONCLUSIONS These data suggest that the modified AOA technique warrants further evaluation as an antimineralization treatment for glutaraldehyde-fixed porcine bioprostheses.