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Interventional Cardiovascular Procedures
M. Michael Swindle, DVM, Professor and Chairman, Department of Comparative Medicine,
Medical University of South Carolina, Charleston, SC 29425
Swine have been one of the primary animal
models for preclinical testing of catheter
introduced devices into the cardiovascular
system.1 This publication reviews the models and
technical procedures that are commonly
employed in these techniques and is
complementary to other publications on this
website.2
Anatomy and Physiology
The gross anatomy of the heart is similar to other
mammals with the exception of left azygous
(hemiazygous) vein which drains the intercostal
vessels into the coronary sinus. Because of this
variation, the coronary sinus is larger than other
species and the blood flow through it is mixed
myocardial and systemic blood. The pig usually
has only two pulmonary veins entering the
atrium. The coronary anatomy is more similar to
the human than most mammals. There is little
preexisting collateral blood supply, consequently,
prolonged occlusion of the coronaries during
interventional procedures will result in a
myocardial infarct. The internal cardiac anatomy
is analogous to that of humans. Sexually mature
Hanford minipigs have the closest heart size and
chamber size to humans of all of the miniature
breeds.1
The peripheral vasculature is similar to most
other animals and humans. The main variation is
the anatomy and size of the external jugular vein.
It is located medial to a line drawn from the angle
of the mandible to the point of the shoulder, at
the same depth as the common carotid artery
and internal jugular vein. The internal and
external vessel depth can be located by
palpation of the ventral surface of the cervical
vertebrae. All three vessels are located at that
depth. It is large in comparison to other veins
and typically has a diameter of 1.5 cm in 50 kg
pigs. The cephalic vein is quite prominent and
superficial as it crosses the neck at the level of
thoracic inlet. Valves are present in the
peripheral veins.
The pig is very prone to vasospasm which can
be prevented by gentle surgical technique and
the use of elastic vessel loops instead of suture
free ties for occlusion of the vessels during
surgery. The veins and arteries in the neck and
the hindlimb can be catheterized using the
Seldinger technique (Figure 1).3
Growth of the pig in projects involving
implantation of devices is a major consideration.
A 35 kg farm pig will grow to >120 kg in six
months with a 35-40 % increase in vessel
diameter and a 25-30 % increase in vessel
length. Unless growth is part of the study then
minipigs should be used for projects >3-6 weeks
in duration. There is a substantial variation in the
growth rates of the minipigs breeds and the
growth charts for the various breeds should be
consulted before selecting the breed, age and
weight of the pig at the start of the study.
Size of the Heart and Blood Vessels
It is frequently necessary to estimate the size of
the heart and blood vessels when planning an
experiment with interventional devices. In
sinclair research
Interventional Cardiovascular Procedures
M. Michael Swindle, DVM, Professor and Chairman, Department of Comparative Medicine,
Medical University of South Carolina, Charleston, SC 29425
general, all pigs of the same weight have similar
vessel sizes. The smaller miniature pigs tend to
have slightly smaller (5%) vessels than farm pigs
of the same weight. Some of the measurements
in the chart were made at necropsy. It should be
expected that in vivo measurements will be
larger by approximately 5-10%. The charts below
provide some guidance:
Technical Considerations
The surgical anatomy and guidelines for
performing vascular surgery, including
intravascular catheter implantation, have been
published on the Sinclair Research Website.2
However, there are some specific considerations
involving the use of interventional devices.
The vessels of the hindlimb and the neck can all
be accessed using the percutaneous Seldinger
technique. Because of the vasospasm that can
be associated with repeated tries at vascular
access using this method, we generally
recommend that if the vessel cannot be
successfully catheterized in three attempts, a
vascular cutdown procedure is performed.
Table 1. Heart Rate to Body Weight (%) of Various Pig
Breeds.
Any procedure involving the implantation of
biomaterials and devices must be performed
using meticulous aseptic technique. The surgical
prep procedures used by our laboratories have
been described.1,2 A key issue is the use of
iodine impregnated sticky drapes as the final skin
site preparation. Antibiotics are not a substitute
for aseptic technique but may be indicated at the
time of surgery if contamination is suspected.
Anesthetics and Adjunct Drugs
1In
vivo measurement using fluoroscopy and contrast
material
2In vitro necropsy measurement
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General anesthetic and analgesic techniques
have been described in detail elsewhere.1,2 As a
general rule, isoflurane should be the default
agent unless it is contraindicated by the protocol.
When procedures involve the heart and great
vessels, caution should be taken to avoid
anesthetic agents that are proarrhythmic or
cardiodepressant. Agents that have been
PO Box 658, Columbia, MO 65205
Tel: (573) 387 4400
sinclair research
Interventional Cardiovascular Procedures
M. Michael Swindle, DVM, Professor and Chairman, Department of Comparative Medicine,
Medical University of South Carolina, Charleston, SC 29425
associated with adverse cardiac events in these
procedures include halothane, xylazine,
tiletamine-zolazepam and propofol.
When performing intracardiac procedures or
catheterization of the coronary arteries,
prophylactic treatment for prevention of
arrhythmias and vasospasm should be utilized
(Table 3). A complete listing of cardiac
emergency drugs and procedures has been
published.1,2
Swine are very prone to development of
ventricular fibrillation when the myocardium is
irritated or coronary blood flow is restricted.
Bretylium (Class III) and amiodarone (Classes I
and III) are antiarrhythmics and either should be
administered IV prior to cardiac manipulation
until the procedure is completed. Amiodarone
has individual variation and the mean arterial
pressure should be monitored and the IV rate
titrated to prevent significant hypotension.
Diltiazem (Class IV) is an antiarrhythmic and Ca
channel blocker useful as prophylaxis prior to
performing intracoronary procedures. It is
generally administered orally the day before the
surgery. Lidocaine infusions are antiectopic and
help prevent vasospasm when the blood vessels
are invaded by catheters. Nitroglycerin may be
administered slowly as an IV infusion at the
aortic root to provide short term vasodilation for
catheterization of the coronaries.1
Anticoagulation is indicated during some
procedures and in the postoperative period when
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some intravascular devices or grafts are
implanted. Aspirin is relatively safe but may be
insufficient for some protocols. If the pig shows
signs of gastric upset, aspirin with Maalox or
separate administration of antacids may be used
to counter the condition. Heparin is generally
administered intraoperatively for short term
anticoagulation by increasing the activated
clotting time (ACT). It is generally not necessary
to administer protamine to reverse it because it
has a short term effect of approximately 45
minutes in swine. Low molecular weight heparin
injections or oral preparations (reviparin,
clopridogrel, hirudin, dalteparin) may be
administered long term for the acute phase of
healing of implanted devices or grafts. Pigs show
a wide individual variation in their sensitivity to
these agents. If a pig is sensitive to the injectable
preparations, bleeding from the injection site is a
frequent occurrence. Changes in the feces
indicative of intraintestinal bleeding should be
monitored for the oral preparations.
The exact dosages of these agents in swine
have not been determined. If a problem with
hemorrhage occurs halt the administration of the
agent and/or reduce the dosage.1 In our
laboratories the most common agents
administered for these effects are aspirin in
combination with clopidogrel and reviparin.
Indomethacin suppositories help prevent the
prostaglandin stimulating effects of some
procedures and help alleviate pulmonary platelet
clotting which can result in pulmonary
PO Box 658, Columbia, MO 65205
Tel: (573) 387 4400
sinclair research
Interventional Cardiovascular Procedures
M. Michael Swindle, DVM, Professor and Chairman, Department of Comparative Medicine,
Medical University of South Carolina, Charleston, SC 29425
hypertension. There can be severe toxic effects
with this agent if it is administered orally or as an
injection. Inserting a rectal suppository the night
before a procedure has been demonstrated to be
safe and effective.1
grafts are implanted in blood vessels. This
condition is similar to that which occurs in
humans, unlike the dog and primate, and more
predictive of the biological behavior of a clinical
implantation. In addition, the hemocoagulation
system pathway is similar to that of humans.
Selected References
1. Swindle MM: Surgery, Anesthesia and
Experimental Techniques in Swine, Ames, IO:
Iowa State University Press, 1998.
2. http://www.sinclairresearch.com/literature.htm
Link on both Fact Sheets and Bulletins for
compete information.
Table 3. Adjunct Agents for Interventional Procedure in
Swine.
Models
Swine have evolved as a primary preclinical
animal model for the testing of intravascular
devices, grafts and procedures. These
procedures have included vascular grafts (Figure
2), stents, angioplasty procedures (Figure 3),
intracardiac shunts, closure devices for
congenital shunts (Figure 3), conduction system
ablation and technical training.1,4 The use of
swine as a preclinical model has been based
upon anatomic, physiologic and practical
considerations.1,2,4 The species provides
relatively large cardiovascular structures and the
size of the heart and blood vessels can be
predicted by weight matching. Swine will develop
neointimal hyperplasia when stents and
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3. Gaymes CH, Swindle MM, Gillette PC, Harold
ME, Schumann RE: Percutaneous
serial catheterization in swine: a practical
approach. J Invest Surg, 8(2): 123-128, 1995.
4. Swindle MM (ed): Swine as Models in
Biomedical Research, Ames, IO: Iowa State
University Press, 1992.
5. Vessel sizes for some of the animals were
provided by personal communication: James A.
Goodrich, DVM, Medical University of SC and
Dagan Harris,MD, Mindguard, Israel.
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Tel: (573) 387 4400