Xenotransplantation - Nonhuman Primates in Biomedical Research - page 387

and heart rate. Easy access to arterial blood also facilitates
monitoring of blood gases and electrolytes.
The administration of fluids and/or drugs through each
catheter is controlled by a pump, which can be pro-
grammed to administer fluids and agents either continu-
ously or intermittently. Up to four different infusions can
be administered through each pump. Therefore, if two
venous catheters are present, up to eight different infu-
sates can be administered simultaneously, if required
(which is quite often necessary in baboons with organ
xenografts). This ensures that the animal is neither over-
loaded with fluid nor dehydrated, and enables drugs to be
administered at intervals without the need for personnel to
be present on all occasions. In our experience, these
pumps have proved reliable and have required little
maintenance.
Occasionally, indwelling gastric catheters have been
used to allow oral medications to be administered and to
facilitate treatment of postoperative anorexia. Anorexia is
relatively common in these animals, often associated with
immunosuppressive agents (or radiation), graft inflam-
mation and/or cytokine release, or, more rarely, pain.
Although providing significant advantages in the
management of the primate, the tether system can be
associated with complications, which include catheter
erosion through a vein wall, infection (particularly as the
animal is immunosuppressed), and hemorrhage following
disconnection of the lines.
Some drugs are available in soluble forms, and can
sometimes be administered orally, particularly to cyn-
omolgus monkeys, though we have found this approach
less successful in baboons. Most drugs and supportive
medications (fluids, electrolytes, glucose) must be given
intravenously in the postoperative period. Indeed, in many
respects care of these animals, following a complex
protocol, is comparable to that of a patient in an intensive
care unit. (More details of critical care of laboratory
animals are included in Volume 1, Chapter 17.)
As rejection can occur rapidly, monitoring of graft
function is necessarily intensive, requiring frequent blood
draws for measurement of complete blood count, metabolic
functions, and immunosuppressive drug levels; monitoring
for infection or sepsis also has to be meticulous. Immu-
nological monitoring includes lymphocyte subset counts
(e.g., T and B cells), anti-pig antibody levels, complement-
dependent cytotoxicity assays, and mixed lymphocyte
reactions.
Following heterotopic heart xenoTx, cardiac function is
monitored by palpation of the graft (2 e 3 times weekly)
through the abdominal wall, electrocardiographic moni-
toring, and measurement of troponin levels at intervals.
Following kidney xenoTx, changes in serum creatinine and
blood urea nitrogen provide most information on renal
function, though urine analysis and urine enzyme assay

FIGURE 16.2 Drawing showing jacket and tether system allowing
continuous or intermittent hemodynamic monitoring, drug and fluid
infusion, and blood sampling in a nonhuman primate without the need for
sedation. Neck or femoral venous and/or arterial cannulae are inserted,
tunneled subcutaneously to the middle of the back, and brought out
through a protective flexible metal tube (held in place by a strong jacket).
The tether system is flexible, allowing the animal free movement within
the cage. (Reproduced with permission from Handbook of Animal Models
in Transplantation Research, Cramer DV, Podesta L, Makowka L (eds).
CRC Press, Boca Raton, 1994.)

( Figure 16.3 A) (or branches of the femoral artery and vein).
They are tunneled under the skin and brought out in the
back, where they are connected to similar catheters within
a flexible metal tether ( Figure 16.3 B). The flexible tether is
connected to the roof of the animal's cage ( Figure 16.3 C),
allowing the catheters to be connected to pumps
( Figure 16.3 D). This allows blood withdrawal and drug
infusion without the need to sedate the animal. A very low
dose of heparin is infused continuously through each
catheter to ensure that they remain patent. (Heparin is also
believed to be beneficial in inhibiting the coagulation
dysfunction that develops after xenoTx.)
During surgical procedures and in the early post-
operative period (e.g., 24 hours), the intravascular catheters
allow monitoring of arterial and central venous pressures