Anticalcification effect of a combination of decellularization, organic solvents and amino acid detoxification on glutaraldehyde-fixed xenopericardial heart valves in a large-animal long-term circulatory model.

Abstract

We aimed to investigate the effect of a combination of anticalcification treatments, which were effective for preventing calcification in a small animal experiment, on glutaraldehyde-fixed xenopericardial valves using a large-animal long-term circulatory model. Valved conduits were made of porcine pericardium as a leaflet and bovine pericardium as a conduit and were implanted into the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were divided into study (glutaraldehyde + combined anticalcification treatment, n = 6) and control (glutaraldehyde alone, n = 9) groups. Upon euthanization at 1 year, echocardiography and cardiac catheterization were performed. Explanted tissues were microscopically examined and analysed for measuring the calcium content. Haemodynamic data were obtained from 3 and 2 goats in the study and control groups, respectively. All valves, except 1, which was limited in motion, were functioning well on echocardiography; pressure gradients across the right ventricular outflow tract were lower in the study group on cardiac catheterization. On gross inspection, all leaflets remained mobile without calcific deposits in the study group, while most leaflets were heavily calcified in the control group. The calcium content in the leaflets remained low (≤4 µg/mg) in the study group. Among the leaflets explanted from goats that survived longer (>3 months), the calcium concentration was higher in the control group than in the study group [15.1 µg/mg (n = 5) vs 2.7 µg/mg (n = 5), respectively; P = 0.008). Porcine pericardial leaflets treated with our anticalcification protocol showed better function and less calcification than those treated with glutaraldehyde alone in the pulmonary position.