Biomedical Engineering Reference
In-Depth Information
(A)
(B)
(C)
(D)
FIGURE 16.3
(A) With the baboon lying supine, with the head turned slightly to the left (under the towel at the left of the figure), the right carotid artery
and internal jugular vein have been identified and isolated. The external jugular vein is isolated separately (not shown), and all three vessels are can-
nulated. (B) The three catheters are tunneled subcutaneously and brought out through the skin of the back, where they are attached to similar catheters
within the flexible metal tether (lower right in figure). The catheters are securely sutured to the skin to ensure they do not protrude below the jacket. (C)
When the baboon is returned to the cage, the tether is connected to the roof of the cage, and (D) the three catheters connected to pumps. (Courtesy of
Burcin Ekser, MD.)
(particularly gamma glutamyltransferase [GGT]) can be
helpful. In addition, ultrasound studies have been found
useful in determining whether the heart remains contract-
ing, or whether blood flow persists through the heart or
kidney. Liver function after xenoTx can be monitored by
frequent measurement of protein synthesis, detoxification,
and coagulation. (Pre-Tx liver failure in the nonhuman
primate can be induced by a variety of toxins [aflatoxins,
alcohol, D-galactosamine] or radiation, although native
hepatectomy often suffices for the needs of the experi-
ment.) In all cases, tissue biopsies are carried out at
intervals, either through an open operative procedure of
by percutaneous transvenous (heart) or percutaneous
fine needle (kidney or liver) techniques; these biopsy
procedures can all be associated with complications,
particularly bleeding.
When islet xenoTx is performed, which is usually into
the portal vein so that the islets reside in the liver, the
intravascular lines are frequently maintained in situ only
during the phase of initiation of diabetes by streptozotocin
until the islet graft is clearly functioning, at which time they
are removed (
van der Windt et al., 2009
). Monitoring of pig
islet function is by frequent measurement of blood glucose
and porcine C-peptide (which can be clearly differentiated
from monkey C-peptide); insulin levels can also be
measured. To measure blood glucose, monkeys can be
monitored by skin prick, and can be trained to cooperate in
this form of monitoring.
Immunosuppressive Therapy
Immunosuppressive therapy, directed against both the
humoral response, e.g., anticomplement agents, such as
cobra venom factor, and the cellular response, e.g., standard
pharmacologic immunosuppressive agents, such as tacro-
limus and mycophenolate mofetil, or the newer co-stimu-
latory blockade agents, such as anti-CD154mAb or
CTLA4-Ig, is usually initiated pre-Tx and continued
throughout the course of the experiment (
Kuwaki et al.,
2005; Tseng et al., 2005
).
Table 16.2
provides an example
of an immunosuppressive regimen with the supportive
therapy required. Increasingly, anticoagulant or antiplatelet
