Purdue University Veterinary Medical
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VOLUME 15, NUMBER 2
May 1990
Current Collaborative Research
SA Surgery and Hillenbrand Biomedical Engineering Center
The academic veterinary clinician has
the opportunity and obligation to channel a
portion of his or her creative energies into
clinical disease problem identification and
problem solving. This may involve direct
application of various treatments to a series
of clinical patients affected by a particular
disease or may require that a problem be
deferred to a laboratory setting for initial
investigation followed by application of
these findings to the clinical patient. Investigation of a clinical problem in a laboratory setting requires collaboration with the
basic scientists who work in the specialty
areas that are key to answering a particular
clinical question. Only when expertise
from all involved areas is present can significant progress toward an answer to a
problem be made.
The abilities of the clinician may also be
used to create and treat animal models or to
study naturally occurring animal diseases
that mimic human diseases to help in the
advancement of human health care. In this
situation, veterinary medicine also benefits, because knowledge is gained by working with the animal model. We would like
to briefly describe our current collaborative
efforts in the investigation of some clinical
problems identified in veterinary and human
medicine.
Canine gastric dilatation-volvulus
A major problem of canine gastric dilatation-volvulus (GDV), which affects up to
60,000 dogs annually, is the unacceptable
mortality rate of 40%. Small animal surgeons, in conjunction with veterinary physiologists, have performed several studies at
Purdue using a dog model to better understand the pathophysiology of GDV. We
have concentrated in the areas of visceral
blood flow alterations and endotoxemia.
Investigators in biomedical engineering
have performed studies to investigate a
paradoxical phenomenon known as reper-
fusion injury. Reperfusion injury is a
complex biochemical reaction that occurs
when transient ischemia is followed by
reperfusion of these ischemic tissues with
normally oxygenated blood, and the result
is the formation of toxic oxygen radicals
which directly cause cell death. Reperfusion injury may be a daily finding to every
practicing veterinarian. The necessary treatment goal of every animal in shock is the
improvement of tissue perfusion by intensive shock therapy. Thus, by striving to
save the life of a patient, the clinician is also
creating a potentially serious condition that
may result in the patient's death. GDV is an
excellent example of shock, and we have
merged the results of our earlier work and
performed two studies of reperfusion injury in a dog model of GDV. We have
proved the presence of reperfusion injury
and have reduced the mortality rate in the
affected dogs by 67% due to specific pharmacologic intervention administered by
intravenous injection to block reperfusion
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injury. The next step in our investigation
process is the application of these findings
to the clinical setting by combining the
experimental treatment with currently used
intensive shock therapy. Funding has just
been obtained to begin a large study of
treatment for reperfusion injury in naturally occurring GDV cases that will be done
with the collaborative efforts of 10 schools
of veterinary medicine. If our laboratory
findings are supported by similar clinical
findings, then an additional 17,000 dogs
annually may survive GDV. On a larger
scale, positive findings will encourage the
application and evaluation of this treatment
for shock from all causes. This clinical
study may also be the very first large scale
clinical trial for reperfusion injury prevention in the medical sciences; therefore,
human medicine may also benefit. Our
collaborating Purdue epidemiologist will
also obtain a large amount of information
from the clinical study that may help in
finding the cause of GDV, as well as predicting its recurrence.
Cardiac assist by skeletal muscle
Congestive heart failure,
secondary to various myocardial diseases, is a major
problem in veterinary and
human medicine. The use
of  repositioned   autogenous skeletal muscle
as a contractile supplement to aid the failing heart is an attractive N&txes
peutic possibility and
is  being
investigated at
wrapped  around  the  heart  (cardiomy-
oplasty). In each configuration, the muscle
is "trained" by a low grade electrical stimulus to convert the more fatigue-sensitive
type of skeletal muscle fibers to fatigue-
resistant type of muscle fibers so that fatigue does not interfer with the muscle's
new function of cardiac assist. After a six-
week training period of electrical stimulation, the muscle is then paced in synchrony
with the heart.   The SMV is contracted
during diastole to move blood out of the
reservoir pouch, around which the muscle
is placed. The cardiomyoplasty muscle is
contracted during systole to help the heart
eject blood. Specialists in pathology, electrical engineering, mechanical engineering, physiology, and veterinary and human
cardiovascular surgeons are consulted in
all these related studies.  We realize that
these procedures will not cure a patient
with congestive heart failure but may allow
for an extension of a good quality of life.
Only cardiomyoplasty has been used clinically in man, and this experience
is very limited. We are currently seeking funding to
study  skeletal  muscle
cardiac  assist  in  a
clinical study using
naturally  occurring heart failure in the dog.
In  addition
to the con-
sultants
listed
above, the
clinical
study will
also require a
biostatistician
and   expertise
from the
Heart
r
Skeletal
muscle
ventricle
several medical   centers
around      the
world. We have
been working in
this area for several
years and are investigating the use of the rectus abdominis muscle configured
as a skeletal muscle ventricle (SMV), as illustrated in Figure 1, and
the use of the latissimus dorsi muscle
4MS
tf -01
veterinary faculty in medical cardiology,
imaging modalities, epidemiology, and continued input from small animal surgery.
The end result of many heart diseases in the
dog and man is global heart dilation and
congestive heart failure which are very
similar between these species; therefore,
we anticipate that our findings will be
relevent to both species. We believe our
laboratory and clinical studies will greatly
benefit both veterinary and human medicine.
Vascular grafts of intestinal submucosa
Vascular surgery, with implantation of
arterial vascular grafts, is very common in
human medicine. However, patency rates
for grafts under 5mm in diameter may be as
low as 49% within four years and infection
of any graft, although infrequent, can have
a devastating outcome with a 75% mortality rate with aortic graft infections and a
50% amputation rate for graft infections
involving the extremities. There is no good
graft material for venous reconstruction.
Patency rates for grafts placed in the low
flow and low pressure venous system are
very poor. We have developed a unique
biological tissue graft material to help
overcome these problems. Our studies, in
a dog model, have shown this material to be
infection resistant, to have a 94% patency
rate for small diameter grafts (femoral and
caratid arteries), a 93% patency for aortic
grafts, and a 100% patency for cranial vena
cava grafts. Current follow-up is from 18 to
30 months after graft surgery. This material is the submucosa of the small and large
intestine. Fresh intestine is harvested, all
layers are removed, and the submucosa can
be directly implanted as a graft or can be
stored for up to one month and then implanted. At the time of implantation the
material is fashioned into a tube the diameter of the recipient vessel. Autografts,
allografts, and heterografts arc being investigated. Intestine submucosa from the dog,
cat, and pig works the best. We are also
collaborating with veterinary immunology,
imaging, mechanical cngineeringand platelet function specialists in the School of
Pharmacy as other studies of this material
as a blood interface are pursued.
All the above projects require extensive
cooperation between many energetic and
talented specialists to accomplish set research goals. However, the new knowledge must then be disseminated in order to
be applied in clinical practice. We rely on
the PUS VM medical illustrators, photographers, and computer and video technicians
to help us do this important job effectively.
Research in the clinical sciences can be
viewed as very boring and time-consuming, or it can be viewed as we have tried to
illustrate from our collaborative studies in
the PUS VM; that is, a very exciting opportunity to contribute to one's profession. It
all depends on perspective. It is certain that
every clinician depends on the results of
today's research/investigative studies to do
their job effectively tomorrow.
Gary C. Lantz, DVM
Stephen F. Badylak, DVM, PhD, MD