Stentless bioprosthetic heart valve research: sheep versus primate model

The mild inflammatory response against stented bioprosthetic heart valves in the sheep model is often opposed by a more distinct response in failing human implants. With the emergence of stentless root prostheses with their significantly larger proportion of tissue interacting with the immune system of the host, a more relevant animal model than the sheep may be needed.

Valved, porcine aortic roots of 5 cm length were fixed in 0.2% glutaraldehyde and implanted in the upper descending aorta of Merino sheep (n = 5; 43+/-3 kg) and Chacma baboons (n = 5; 17+/-3 kg). After 6 weeks of tissue calcification, pannus outgrowth and inflammation were assessed by atomic absorption spectrophotometry, histologic damage scoring (0 to 3), image analysis, and transmission electron microscopy.

The main difference between the two animal models was in aortic wall calcification (64.8+/-39.8 microg/mg in the sheep model versus 4.1+/-5.9 microg/mg in the primate model; p > 0.005). In both models, leaflet calcification was negligible (2.6+/-2.4 microg/mg in the sheep versus 2.5+/-1.9 microg/mg in the primate), and the overall extent of inflammation was comparable (1.2+/-0.8 versus 0.98+/-0.7; p = 0.18 in the sheep and the primate, respectively). Qualitatively, the sheep demonstrated a macrophage-dominated reaction whereas the inflammatory demarcation often resembled a granulocyte-dominated xenograft response in the primate. Pannus outgrowth was comparable in length (8.4+/-2.3 mm versus 9.1+/-4.3 mm proximally and 7.1+/-3.4 mm versus 7.4+/-5.1 mm distally, in the sheep and baboon, respectively; p > 0.05).

Our results confirm the sheep as a significantly stronger calcification model for stentless aortic heart valves than the primate. Remaining antigenicity of porcine tissue as a result of incomplete cross-linking, however, elicits a distinctly stronger xenograft-type reaction in the primate model.