Biomedical Engineering Reference
In-Depth Information
and animal age (Flameng et al., 2006). While juvenile sheep have an aggressive
calcification response, their rapid growth during the 150 day study results in
hemodynamic complications due to valve±annulus mismatch. Flameng corre-
lated results in juvenile sheep to results in adolescent sheep, where sheep are 8±
11 months old. At this age, the growth rate of the animal has slowed, so it will
not outgrow the valve during the study duration, greatly reducing the com-
plications associated with valve±annulus mismatch. The calcification response
of the adolescent animal is reduced compared with a juvenile animal, but it will
still calcify, and the relative level of calcification between common valves is
still evident. This also provides a more representative assessment of the
hemodynamic performance of the valve (Flameng et al., 2006).
While large animal models enable evaluation of the finished valve in the
orthotopic position, it is expensive and not amenable for research purposes.
Towards that end, Drs Schoen and Levy have popularized the application of the
rat subcutaneous implant model, which has become the most commonly used
small animal model (Levy et al., 1983). Briefly, young rats are used, 21±28 days
old, and strips or coupons of processed tissue are implanted subcutaneously in
the abdomen or across the back, with multiple samples implanted in each
animal. This enables a direct comparison of test and control materials in the
same animal, an important feature, as there can be significant between-animal
variability in calcification levels.
5.6.2 Baseline calcification levels
Baseline levels of calcification were determined from clinical explants, which
were analyzed in much the same way as the animal study explants. Evaluating
valves which were explanted due to dystrophic calcification, Schoen et al.
(1987) report that as little as 67 and 34g calcium/mg dry tissue weight were
sufficient
to result
in clinical
failure in the aortic and mitral positions,
respectively.
To date, evaluation of materials and processes in various models have
revealed that the initiating sites of calcification are associated with cell mem-
branes, which come from endogenous degenerated cells and infiltrating cells
once implanted in the host (Harasaki et al., 1986). Additional sites of calcifica-
tion include insudated proteins (sometimes called the sponge phenomenon),
collagen and elastic fibers (Schoen and Levy, 1986), and bacterial remnants
(Levy et al., 1977; Rumisek et al., 1985). Calcification begins very quickly upon
implantation, within 48 hours (Schoen et al., 1986). These deposits are visible
only ultra-microscopically at first, but the calcium deposits grow in size and
number with time (Schoen et al., 1994). Porcine aortic leaflets and bovine
pericardial tissues calcify similarly. An in-depth protocol for explants analysis
has been published (Schoen, 1995).
