ANIMAL FOR STENTS OR STENTS FOR ANIMALS – AN AREA UNDER CONSTRUCTION (PART II)

Abstract

The stent used in clinics is broadly classified on the basis of a number of different parameters, however organ based classification is considered in the current part of review literature. A huge amount of literature related to the stenting using animal models available in PubMed has been reviewed over the last 10 years to draw the trend in development and usage of stent in various animal models. This shows that the rate of development in biomedical models is not implemented in clinics due to less awareness and expertise. We hope that the data gathered and sorted in current review may provide a clue to solve the issue of translation of this novel technique.

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Patil PB et al. / Journal of Science / Vol 4 / Issue 7 / 2014/ 437-445.
437
e ISSN 2277 - 3290
Print ISSN 2277 - 3282
Journal of Science Veterinary
www.journalofscience.net
ANIMAL FOR STENTS OR STENTS FOR ANIMALS – AN AREA
UNDER CONSTRUCTION (PART II)
Patil PB1, Talekar SH*2, Patil DB3, Parikh PV4, Patel AM5
1
Post-doctoral Research Associate, Laboratory for Transplantation Biology & Regenerative Medicine,
Department of Surgery, Gothenburg University, Sweden.
2Associate Professor and Hospital Superintendent, Teaching Veterinary Clinical Complex (T.V.C.C.) JAU, Junagadh,
Gujarat, India-362001.
3Professor & Head, Dept. of Surgery and Radiology, Veterinary College, Anand, Gujarat, India-388001.
4Professor, Dept. of Surgery and Radiology, Veterinary College, Anand, Gujarat, India-388001.
5Assistant Professor, Teaching Veterinary Clinical Complex (T.V.C.C.) JAU, Junagadh, Gujarat, India-362001.
ABSTRACT
The stent used in clinics is broadly classified on the basis of a number of different parameters, however organ based
classification is considered in the current part of review literature. A huge amount of literature related to the stenting using
animal models available in PubMed has been reviewed over the last 10 years to draw the trend in development and usage of
stent in various animal models. This shows that the rate of development in biomedical models is not implemented in clinics
due to less awareness and expertise. We hope that the data gathered and sorted in current review may provide a clue to solve
the issue of translation of this novel technique.
Keywords: Models for stenting, Veterinary stent, Organ stent and Vascular stent.
INTRODUCTION
Minimally invasive therapeutics in comparison
to the traditional open surgical approaches is precise and
helps to adhere ‘Tenets of Halsted’. It not only allows
maneuvers through small incisional wounds, but also
shortens anesthesia time. This prevents self-mutilation in
animals due to less pain compared to traditional
approaches. Similarly, it needs less handling of tissue,
avoiding the chance of infection and contamination both
in general and also iatrogenic by reducing the duration of
stay in hospital or clinics. In addition, it also renders
manipulation at the place, which is inaccessible with
traditional surgeries.
In brief if we look at organ-wise stent
classification and its use in clinics, it reveals interesting
data about which field is less explored or reached clinics.
Esophageal stent
Minimally invasive stents are used in obstructive
esophageal cancer of 5-8 diameters, which are difficult to
remove through endoscopy [1]. Esophageal stent helps as
palliative treatment, which improves patient’s life.
However, sometimes it ends with complication known as
bird nest deformity [2]. Esophageal strictures treated with
stenting allow easy passage for ingesta and less
discomfort for the patient and veterinarian, which does
not need repeated dilatation. Stenting for esophageal
stricture has shown decreased the necessity for repeated
interventions in comparison with balloon dilation.
Colonic stent
Usually metallic colonic stents are used to treat
benign or malignant Crohn’s stricture, colo-vesical fistula
etc. It improves quality of life for patients.
Tracheal stent
Most of small breeds (Apso,Chihuahua, Lhasa,
Maltese, Pomeranian, Poodle, Pug, Shih and Yorkshire
Terrier) [3] of the canine family suffering from tracheal
collapse (intra-thoracic or extra-thoracic) shows
symptoms of chronic cough, increasing respiratory efforts
Corresponding Author:- Shivaji Talekar Email:- Shivaji.talekar@gmail.com

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and events of dyspnea. Medical management is the
treatment of choice and surgical repair is chosen when
animal do not react well to the treatment. Minimally
invasive approach of endotrache al stenting is a
promising new therapy under trial with challenges of new
complications [4].
In human patients, it has been found with few
complications viz., granulation tissue, stent migration,
stent expectoration, halitosis, mucous retention and mucus
plugging [5]. Whereas in dogs, minor and brief bleeding
[6] that occurred duringairway bypass stent placement,
fractured tracheal stent [7].
Ureteral stent
Pyelonephritis due to urolithiasis in animals is
very common and mostly undiagnosed due to lack of a
routine checkup. However, this has tremendous potential
to develop progressive chronic kidney diseases, which
may lead to systemic bacteremia and death.
Cats are prone to severe complications after
surgical removal of uroliths (>30%). Post-operative
ureteral stents have been effective in relieving ureteral
obstruction in both dogs and cats with less post-operative
morbidity and mortality [8].
Ureteral stenting is a useful technique to relieve ureteral
stenosis caused due to severe urethral strictures in dog[9]
and cats[10], traumatic penile urethral stricture (in dog)
[11]. However, few complications are need to be
considered while using such techniques viz., risk of
iatrogenic tumor seeding (in dog) [12] intermittent
hematuria (in cat) [13]. Although stenting has a few
hurdles of limitations and compilations, in overall it
improves the quality of life in animals having poor
prognosis [14].
A combination of a biocompatible polymer on
metallic stents (tremendous strength), provokes a minimal
immune response when placed into the urinary tract to
maintain ureteral luminal patency [15].
Urethral stent
Urethral self-expanding metallic stent (SEMS)
has been an effective tool in obstructive carcinoma of the
feline [16] and canine urethra which significantly
increases the median survival time [17].
Vascular stent
Regardless of huge achievement in vascular stent
field compared to other organ stents, it is still limited to
biomedical research and human patients. The important
impediment lies in the early diagnosis of vascular
ailments in animals.
That’s why, although we see that stent field has
been widely explored in research (pig, dog, rabbit and rat
as biomedical models) but very few clinical cases are
performed and reported.
Minimally invasive surgeries (MIS) involve
laparoscopy; thoracoscopy, Endourology and
Interventional Radiology (IR) are a boon for veterinary
field as it relieves quickly, easily and safely. Among these
IR is least invasive methodology of treatment modality
where catheter guided stent delivery has a lion’s share.
Potential applications of catheter guided techniques for
the management of veterinary diseases is boundless. A
number of applications possible using catheter-guided
system is shown in a number of studies viz., pulmonary
valve implantation [18], percutaneous valve stent
insertion to correct the pulmonary regurgitation in sheep
[19]. On Google search, found VET-STENT® series,
which are optimized stents, especially for veterinary
applications. They are self-expanding Nitinol stents in
various sizes and designs. Three different models
available (trachea, inferior vena cava and urethra)are
compatible with magnetic resonance (MR) [20]. It shows
that stent field is yet to not reach to the clinic as common
as expected due less commercial involvement.
Experimental Studies
A number of animals are being used for
experimental and preclinical studies of vascular and organ
stents but most commonly used animals are dog, rabbit
and pig. Use of biomedical models in preclinical studies
has added an enormous amount of information about
different stents. We scanned articles on PubMed for last
10 year and found 1308 articles published online
regarding stent experiments using animal models. After
sorting them, plotted graphs per year as per species used,
material used, organ targeted or eluting drug for last 10
years in four graphs (Graph 1-3).
Interestingly, it seems that porcine model uses a
lot followed by rabbit in stent research. Again, bio-
absorbable material as base material for stent is increasing
compared with BMS (bare metal stent) mostly steel or
cobalt chromium. Eluting drugs area common trend and
accepted method, which has revolutionized the whole
field. Starting from simple antithrombotic drugs,
antimitotic drugs till nanoparticles, stem cells, and
antibodies have been tried as eluting material in stents.
However, sirolimus and paclitaxel are often used as
standards in many studies. Most of this stent research has
carried out in the vascular field as it’s more demanding
for humans (Graph 1-3).
Canine (dog) model has been used in many
cardiovascular stent evaluation studies more often in
China, Korea, USA, Japan and Spainare to name among
the few. Stenting has been performed in bile duct [21],
coronary artery[22], larynx [23], tracheal lumen [24],
bronchus [25], esophagus [26], AVF, jugular vein, carotid
artery [27], (Abdominal/infrarenal/ thoracic) aorta [28],
renal artery [29], deep femoral artery [30], iliac artery
[31], portal vein [32], urethra [33], pancreas [34].

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Swine (pig) model has been used for a very long
time, mostly in USA, Germany, China, Japan, Canada,
Brazil, Finland, Switzerland, Belgium and many others,
however now a days a trend of using mini-pigs are more
practical and economical for long-term experiments. The
number of researchers have used the pig as a biomedical
animal model for number of organ stents e.g. pancreatico-
biliary tree [35], coronary artery [36], esophagus [37],
AVF, jugular vein, carotid artery [38], (Abdominal/infra-
renal/ thoracic) aorta [39], renal artery [38], iliac artery
[40], ureter [41], bronchus [42], portal vein [43], deep
femoral artery[44], colon [45], lung [46], aortic valve
[47]. Rabbit and rat model require relatively
challenging skills, especially in vascular stenting
experiments due to its size and type of models used
possible procedural complication (Fig.1& Table 1).
However, they are preferred due to cost-effective and
easy in handling. Models used in different part of the
world (especially in Turkey, India, China, Korea, China,
Japan, Taiwan, Canada are to name among the few) for
different organs viz. Bile duct [48], external iliac arteries
[49], urethra [50], esophagus [51], jugular/carotid vessels
[52], knee joint [53], aorta [54] and ureter [55].
Similarly, in rat models, different stent have been
used (especially in Korea, Italy, USA and Australia to
name among the few) for different sites or organs e.g.
Intestine [56], aorta [57], ureter [58], esophagus [59],
trachea [60], urethra [61], carotid [62], subcutaneous [63],
portal vein [64] and pancreas [65].
All these models are used to evaluate the
efficacy and compatibility of newly developed stents
either for humans or animals (mostly for human use).
Evaluation can be from day 7 till years; however, mostly
few months have been considered enough to predict long
term effects in human. This is due to small life span and
rapid vascular response in animals compared to human.
Swine model is mostly used due to its resemblance with
human lesions in terms of vascular response. Cats have
not proven to be a broadly suitable model due to
atheromatous lesion is different distribution and
characteristics. Since, cat is a good model for biliary
ailments (represent biliary problems similar to human), so
can be considered as an ideal model for biliary stenting as
well. Neither have dogs been extensively used in
atherosclerosis research, although widely used in
cardiovascular and surgical studies. Hypothyroidism must
be induced to overcome the natural resistance of dogs to
hypercholesterolemia or lesion development. Rabbit are
used for lesion characterization, drug interactions and
mechanical arterial injury due to economy, size (enough
big to operate or evaluate comfortably), shorter duration
for disease-induction, availability and ease in handling
and rat are used due to their small size, possibility of easy
monitoring and using controlled parameters in
mechanistic study (knockout animals) however rodent
model in general, has disadvantage of different
lipoprotein profiles to man and smaller vessel size.
Smaller vessel sizes not only results in different arterial
wall morphology, but also difficult to perform certain
surgical interventions viz., balloon catheterization [66].
Evaluation of stent in model
Usually, animal study provides lesions much
faster depending on species, breed, nutrition and type of
model. Location of implanted stent matters in the in vivo
monitoring of stent. Implanting procedure and handling of
stented vessel samples during retrieval are vital to the
lesions observed in stenting experiments. A proper
guideline [67] need to be considered in evaluation results
of stenting in experimental models, which are vital for
future clinical implantation during this stent war (too
rapid progress to evaluate). A wide variety of parameters
can be considered for evaluating efficacy, however, most
common are neointimal hyperplasia (NH), luminal
narrowing (LN), (apparent) re-endothelisation (RE), peri-
strut inflammatory response (PIR), internal elastic lamina
disruption (ILD) and non-obstructive peri-strut fibrin
(NOPF) as used in our previous experiment(Graph 4) to
evaluate stent efficacy [68, 69].
From bench to bedside
Few of the published works (30 publications)
found on PubMed, is cited in this article, however, there
is much more data and cases done all over the world
which are not reported or documented. Especially in
India, where we need to deal with urological cases much
more than the rest of the world. In such cases, we required
to focus on better quality of treatment and better quality in
the life-style of the animal. We believe that the huge
number of challenging cases involving tracheal,
urological and udder injuries in caprine and bovine
species will get help from stenting field, quite soon.
Most of the reported cases are either performed
in canine or feline, largely in USA (Table 2). Few
techniques have been used in pisces and birds e.g. A case
of subcutaneous emphysema resolved in a Griffon
Vulture chick (Gyps fulvus) using stent[70].Previously,
stent was used as scaffolding device to support stenosed
hollow tissue, which has later added with the treating of
weak, tear, defective, damaged cancerous tissues. Stent
has also been used for ablation of benign lesions or
malignant tumors of hollow viscera using radiofrequency
ablation from gastrointestinal, biliary, and urinary tract
[71]. Earlier, it was used only as anaphylaxis, but
nowadays, it is used as prophylaxis e.g., prophylactic after
gastro-duodenostomy [72].
In a nutshell, use of stent either organ or vascular
can become a clinical routine only if the knowledge
gained in preclinical research and clinical cases of major
universities is put together with commercial investors.

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Figure 1. Fluoroscopic images of antegrade iliac
(vascular) stenting in rabbit model
Stenting/Percutaneous approach has been shown
advantages in a number of cases, including: - (i)
Oncological cases (Trans-arterial chemoembolization or
palliative radiotherapy or chemotherapy of neoplastic
diseases of vital tissue or organs, Stenting of malignant
urethral or ureteral obstruction. Stenting for stenosed
lumens due to malignancy in vessels, airway,
gastrointestinal tract, where open surgery is
contraindicated).(ii) Nutritional cases (Placing naso-
jejunal feeding tube, percutaneous gastrostomy tube,
percutaneous gastrojejunostomy tube, esophago
jejunostomy tube) (iii) Urinary cases (Tube / stent
placement for as percutaneous nephrostomy tube, ureteral
or urethral stent for urolithiasis traumatic disruption or
iatrogenic or malignant obstruction.) (iv) Mixed cases
(Foreign body removal in vessels, trachea or bronchi;
Glue embolization of hepatic arterio-venous
malformations, thoracic duct, biliary drainages, nasal
epistaxis. Stenting in esophageal stricture, repair of
complex vascular malformations, balloon peri-cardiotomy
for recurrent pericardial effusion. In-dwelling drainage
catheters with subcutaneous access port) [73]. Also, if the
value issue and training aspects are taken care, no sooner
it will be enforced in companion than in farm animals.
Stent war
The rate at which the stent market is expanding
in general, it has become a challenge to track and
implement it in the veterinary field or the medical field. It
is very important to evaluate a product well before being
used so demands active research in veterinary, which is
lacking. The irony of the field is, animal models are
extensively used to evaluate every product of stent used in
medical (human) field, but hardly very few products are
available for use in the veterinary field.
The risks related to DES placement are marginal
compared to the untreated stents or conventional methods
of treating the diseases with conventional therapy
involves dual systemic therapy carrying several
disadvantages e.g. Irregular dose and dosage to the
targeted site, side effects, contraindications, high grade
responsibility, exasperating follow-up treatment,
uncertainty and unreliability. Recent literature concerned
with coated stents shown a diminished rate of occlusion
(stenosis), thrombosis and even reduced the requirement
of systemic medication and follow-up.
Many stenting procedures need advanced
imaging modalities, however; fluoroscopy could be a vital
tool for most of the stenting procedures. In stenting, an
array of guide wires with numerous properties. Stenting
catheters are specifically tailored for specific procedures,
stents composed of various materials and designs, which
replaces the quality of surgical pack. It is ought to be
noted that several of the already developed veterinary
stenting procedures might end in vital hurt or maybe
death, without prior experience.
Table 1. Complications in vascular stenting in rabbit model of antegrate-iliac stenting
Rabbits (n)
Post Mortem Observations
1
Anaesthetic over dosage and stress leading to dyspnoea and death.
2
GW injury in heart.
1
Blood loss due to slippage of carotid artery ligature during post stenting.
1
GW injury in external iliac artery
1
GW injury resulted in internal bleeding and rupture of posterior aorta as a result of
loop formation of GW due to deployment of one of the stent at branching of
posterior aorta
1
Excessive haemorrhage during angiography
1
Blind stenting (Tripping of electric supply) resulted in intussusception and rupture of
iliac artery due to incomplete stent deployment at 6 atm pressure.

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Table 2. Few clinical cases of stenting in animals reported as publication (A-G)
Clinical cases of stenting
Country
Location
Material
Species
Reference
A. Esophageal stents
UK
Single cervical esophageal
stricture
Biodegradable self-expanding
Feline
[74]
USA
Esophageal squamous cell
carcinoma
Self-expanding metallic stent
Canine
[75]
Germany
Single cervical esophageal
stricture
Self-expanding metallic stent
Feline
[76]
USA
Benign esophageal stricture
Balloon dilatation only
Canine,
Feline
[77]
B. Colonic stents
USA
Colorectal neoplastic
obstruction
Nitinol stent
Canine
[78]
USA
Colonic adenocarcinoma
Self-expanding metallic stent
Feline
[79]
C. Tracheal stents
USA
End stage tracheal collapse
Nitinol
Canine
[80]
Spain
Tracheal collapse
--
Canine
[4]
USA
Tracheal collapse
Nitinol
Canine
[81]
USA
Tracheal collapse
Nitinol
Canine
[82]
Korea
Obstructive diseases of trachea
Silicone
Canine
[83]
Canada
Tracheal collapse
Nitinol
Canine
[84]
USA
Tracheal collapse
Nitinol
Equine
[85]
D. Nasopharyngeal stents
USA
Bilateral bony choanal atresia
Temporary stenting
Feline
[86]
USA
Nasopharyngeal stenosis
Metallic stent
Feline
[87]
USA
Recurrent nasopharyngeal
stenosis
(2-cm) braided-wire
endoprosthesis
Feline
[88]
E. Esophageal stents
Japan
Carcinoma of bladder neck and
prostate
Normograde fashion via
percutaneous puncture
Canine
[12]
Italy
Ureterotomy/Ureteroliths
removal surgery
3 French double-J catheters
Feline
[10]
USA
Proximal ureteral stenosis
2 double-pigtail ureteral stents
Canine
[89]
USA
Intra-corporeal lithotripsy /
Ureteral calculi
A 4.8-Fr, 26-cm double-pigtail
ureteral stent
Pisces
(dolphin)
[90]
F. Urethral stents
Korea
Post-surgical urethral stricture
SEMS with ePTFE*
Canine
[9]
USA
Traumatic urethra rupture
SEMS
Feline
[13]
USA
Traumatic stricture of penile
urethra
SEMS, Nitinol coating
Canine
[11]
USA
Urethral obstruction secondary
to transitional cell carcinoma
(TCC).
SEMS, Nitinol coating
Canine
[14]
USA
Obstructive carcinoma
SEMS
Canine
[17]
USA
Malignant urethral obstruction
Balloon expandable metallic
stent
Canine
[91]
Australia
Malignant urethral obstruction
SEMS
Feline
[16]
Korea
Refractory lower urinary tract
obstruction.
SEMS
Feline
[92]
USA
Malignant urethral obstruction
SEMS
Feline
[93]
G. Caval stents
USA
Venacava
Caudal vena caval obstruction
Feline
[94]

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442
Graph 1. Species-wise stent publications
Graph 2. Year-wise research in eluting stents
Graph 3. Organ-wise stent publications
Graph 4. Graded histological endpoints for evaluation
stent (DDES) patency and tissue related response in
rabbit model
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