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Creation of a Tricuspid Valve Regurgitation Model from
Tricuspid Annular Dilatation using the Cardioport
Video-Assisted Imaging System
Eva Maria Delmo Walter1,2, Nikolay V. Vasilyev1, Bjoern Sill1, Muralidhar Padala3,
Jorge Jimenez3, Ajit P. Yoganathan3, Roland Hetzer2, Pedro J. del Nido1
1
2
Department of Cardiac Surgery, Children’s Hospital Boston/Harvard Medical School, Boston, Massachusetts, USA,
Deutsches Herzzentrum Berlin, Berlin, Germany, 3Georgia Institute of Technology, Atlanta, Georgia, USA
Background and aim of the study: Experimental models of tricuspid valve regurgitation (TR) are used to
study novel annuloplasty techniques (including
prosthetic rings), and they can also serve as physiologic models to investigate TR pathophysiology. The
study aim was to develop an appropriate simple and
reproducible experimental model of TR from annular dilatation.
Methods: Acute TR was successfully created through
multiple small 3- to 5-mm incisions in the annulus
using a custom-made optical port with an instrument
shaft (the Cardioport) that accepts a standard endoscopic imaging system. The Cardioport was inserted,
via a thoracotomy, through the right atrium of seven
Yorkshire pigs, and directed towards the tricuspid
valve annulus to create the annular incisions.
Tricuspid valve anatomy and function were evaluated using 2D and 3D echocardiography. The presence
and severity of TR, annulus diameter, and changes in
heart rate and atrial pressures after making the annu-
lar incisions were documented. To monitor tricuspid
annular dilatation and the progression of TR, follow
up echocardiography and color Doppler examinations were performed at two and eight weeks postoperatively.
Results: The acute onset of TR was well tolerated,
and there were no deaths or significant morbidity
associated with the procedure. The annular diameter
was increased from a preoperative mean of 23.1 ± 1.7
mm, to 32.2 ± 2.5 mm at two weeks postoperatively,
and to 37.3 ± 3.6 mm at eight weeks postoperatively.
Overall, the TR progressed from mild (grade I) to
severe (grade III) in all of the animals.
Conclusion: This novel porcine model represents a
relatively simple and a reproducible surgical technique for the creation of annular dilatation and TR,
and may also serve as a chronic model of the latter
condition.
In the past, relatively few methods have been
described for the creation of subacute valvular insufficiency in animal models. Those presented usually have
limitations, such as permanent destruction of the valve
leaflets or chordae, or a lack of control over the degree
of regurgitation produced. Previously, the creation of
acute tricuspid regurgitation (TR) has been achieved
mainly by using surgical techniques, with the objective
of studying the influence of TR on heart hemodynamics or the function of other organs (1-4).
Likewise, a percutaneous approach to the creation of
TR has been described in a canine model by avulsing
the papillary muscles using a biotome (5), and in a similar ovine model by using a catheter (6). However,
these were acute studies, as the sudden onset of severe
TR was not well tolerated and hence the use of such
models to evaluate chronic TR was not pursued. For an
evaluation of the effects of tricuspid annular ring
implantation to correct regurgitation, a progressive but
stable chronic animal model is required. hence, the
study aim was to develop a simple and reproducible
experimental model of progressive TR from annular
dilatation.
Presented at the 39th Annual Meeting of the German Society of
Cardiothoracic and Vascular Surgery. 18th February 2010, Stuttgart,
Germany
Address for correspondence:
Eva Maria B. Delmo Walter, Children’s Hospital Boston, Harvard
Medical School, 300 Longwood Avenue, Boston, Massachusetts
02115, USA
e-mail: [email protected]
The Journal of Heart Valve Disease 2011;20:184-188
Materials and methods
Animals
Seven Yorkshire pigs (average body weight 40 kg)
were sedated with intravenous ketamine hydrochloride
(0.9 mg/kg; Fort Dodge Animal Health, Fort Dodge,
© Copyright by ICR Publishers 2011
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A
B
C
Figure 1: A) The Cardioport with the imaging system. B)
Creation of the incision on the tricuspid valve annulus, as
viewed from the right atrium using the Cardioport imaging
system. C) Tricuspid valve, showing the areas where
multiple small incisions and additional incisions were
placed. In this way, important landmarks such as the
bundle of His and atrioventricular (AV) node are avoided.
Iowa, USA) and midazolam hydrochloride (0.05
mg/kg; Bedford Laboratories, Bedford, Ohio, USA).
Atropine sulfate (0.02 mg/kg; American Regent
Laboratories, Shirley, NY, USA) was also administered
intravenously. The animals were administered 5%
isoflurane (Isothesia; Burns Veterinary Supply,
Rockville Center, NY, USA) via a mask until they were
Experimental tricuspid regurgitation
L. Walter et al.
185
intubated. Following intubation, the anesthesia was
maintained with 2-2.5% isoflurane mixed with oxygen.
Arterial pressure lines and venous pressure lines for
monitoring were placed percutaneously in the femoral
artery and veins, respectively. Enrofloxacin (2.5 mg/kg;
Bayer Health Care LLC, Shawnee Mission, KS, USA)
was administered intravenously after induction of anesthesia, and a further dose was given postoperatively.
The study protocol was approved by the Children’s
Hospital Boston/Harvard Medical School Animal
Care and Use Committee.
Surgical technique to create tricuspid regurgitation
Under general anesthesia, the animal was placed in
the right anterolateral thoracotomy position, the chest
and back were shaved and prepared with povidoneiodine, and sterile drapes were placed in position. An
anterolateral thoracotomy incision was made at the
third intercostal space, after which the pericardium
was incised, sparing the phrenic nerve, to expose the
heart. The heart structures (superior and inferior vena
cava and right atrium and appendage) were identified,
and a purse-string suture (Prolene 4-0) was placed
around the atrial appendage.
The Cardioport (Fig. 1A), which was developed in
the experimental laboratory of the Children’s Hospital
Boston/Harvard Medical School, and used previously
for intracardiac beating-heart procedures (7), was fitted with a standard video-endoscopic equipment
imaging system (Smith and Nephew, Dyonics, Inc.,
Andover, MA, USA) and a 5-mm rigid 30° telescope
(Karl Storz GmbH & Co. KG, Tuttlingen, Germany).
The unit was introduced into the right atrium and
secured with a Rommel tourniquet. Intraoperative epicardial echocardiography using the X7-2 matrix transducer on an IE33 system (Philips Healthcare, Andover,
MA, USA) was carried out to determine the right atrial and right ventricular sizes, the function of the tricuspid valve, and the annular dimensions.
Under echocardiographic guidance and direct cardioscopic imaging, multiple (five to ten) small incisions (each of 3-5 mm) were placed circumferentially
along the tricuspid annulus, avoiding delicate structures such as the atrioventricular node, the tendon of
Todaro, and the Bundle of His (Fig. 1B and C).
Intraoperative echocardiography was performed to
determine if TR had been induced and, if not, then a
further three to five small incisions were added until
mild to moderate TR was observed when using color
Doppler interrogation. The presence and severity of
regurgitation, the diameter of the annulus, and
changes in the heart rate and right atrial pressures after
annular incisions, were each documented. After confirming that no damage had been caused to the valve
leaflets or subvalvular apparatus, the cardioscope was
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L. Walter et al.
fentanyl patch (Ortho-McNeil-Janssen Pharmaceutical,
NJ, USA) was applied to the back of each animal to
provide postoperative analgesia. When awake and
recovered, the pig was returned to the animal house in
a stable hemodynamic condition, with all pressure
lines and chest tubes having been removed.
Cefuroxime (500 mg twice daily) was administered
orally for three days to each pig as antibiotic cover.
Two-dimensional (2D) and three-dimensional (3D)
echocardiography with color flow Doppler were performed at two and eight weeks postoperatively to
monitor the progression of annular dilatation and the
severity of the TR.
A
Statistical analysis
All data were analyzed using SPSS 16.0 (SPSS Inc.,
Chicago IL, USA) software. The data were expressed
as absolute frequency values, and continuous data as
mean ± SD, as appropriate. Time-related events were
examined using the Friedman test at 95% confidence
intervals (CI).
B
Results
Figure 2: A) Preoperative echocardiography showing a
normal right atrial and right ventricular anatomy, with
normal valve leaflet morphology, mobility and without
prolapse, and normal annular diameter. B) Post-incision
onset of acute tricuspid regurgitation
withdrawn from the right atrium, and the purse-string
suture with additional sutures if necessary. Chest tubes
were placed along the pleural space, and the posterior
pericardium and pericardium were closed. The ribs
were approximated and chest was closed in layers. A
Preoperative echocardiographic studies showed normal right atrial and right ventricular anatomies, with
normal valve leaflet morphology, mobility and without prolapse in all animals (Fig. 2A). There was no tricuspid regurgitation, and the mean annular size was
23.1 ± 1.7 mm (range: 21 to 25 mm). The successful creation of acute TR was documented and quantified with
continuous-wave and color Doppler echocardiography (8) (see Table I and Fig. 2B). The TR was well tolerated by all animals, and no morbidity or mortality
was recorded.
Echocardiographic studies conducted at two and
eight weeks postoperatively demonstrated a progressive increase in the annular dimensions (Figs. 3A and
4A). Postoperatively, the mean annular dimension was
32.2 ± 2.5 mm (range: 27 to 36 mm) after two weeks, and
37.3 ± 3.6 mm (range: 36 to 43 mm) after eight weeks.
The TR also increased progressively in severity (Figs. 3B
and 4B), from a mean grade of 1.6 ± 0.5 to grade 3 in all
animals, at two and eight weeks, respectively.
Table I: Severity of tricuspid regurgitation (TR): Echocardiographic data and Doppler parameters.
Parameters/location
Jet area-central jet
(cm2)
Jet density and jet
continuous wave
Severity of TR
Mild
Moderate
Severe
<5
5-10
>10
Soft and
parabolic
Dense, variable
Transparent,
triangular (with
early peak)
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J Heart Valve Dis
Vol. 20. No. 2
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A
187
A
B
B
Figure 3: Postoperative increases in (A) the annular
dimensions and (B) the severity of tricuspid regurgitation.
Figure 4: A) Development of annular dilatation over time.
B) Development of TR severity over time.
Discussion
The animal model developed to create TR by inducing
annular dilatation with multiple small annular incisions
is relatively simple, does not require cardiopulmonary
bypass, avoids injury to the valve leaflets or subvalvular apparatus and, in the present authors’ experience,
was not associated with complications. The model was
easily reproducible, and resulted in a predictable progression of TR. Notably, the technique does not involve
technical complexities such as laceration of the valve
leaflets, transection or avulsion of the papillary muscles
or chordae tendineae, nor suture ligation of the valve
leaflets (3,4,6). Such previously described techniques all
have the limitation of causing permanent damage to the
critical valve structures, and they also lack control over
the degree of TR produced. The concept of annular incisions has been described previously, though only in an
ex vivo model with the mongrel dog heart to develop
modifications of the DeVega annuloplasty technique (1).
The present model was created in the beating heart, and
the results obtained describe the progression of TR with
this technique in a porcine model.
The multiple surgical incisions, as made in the present study, can be placed with accuracy around the
annulus, and controlled precisely by employing a combination of ultrasound imaging and the Cardioport
optical imaging system. The multiple annular incisions
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eventually induced progressive annular dilatation
over time, which led consequently to an increasing
severity of the TR. Moreover, the process was easily
monitored by using serial transthoracic echocardiography. Importantly, echocardiographic imaging at follow
up showed that no injuries had occurred to either the
valve leaflets or the subvalvular apparatus.
The present animal model could be used for hemodynamic studies of acute TR as well as for the evaluation of chronic TR, and the effect of surgical or
catheter-based interventions. This novel in vivo
porcine model may be used to facilitate research on the
development of annuloplasty rings to treat annular
dilatation, or potentially to create novel procedures for
the treatment of tricuspid valve dysfunction.
In conclusion, this novel in vivo porcine model is safe,
relatively simple, easily reproducible, and provides
predictable results, allowing the creation of TR from
annular dilatation, without significant associated morbidity or mortality.
Acknowledgments
Funding for the development of the Cardioport was
provided by grants from the Center for Integration of
Medicine and Innovative Technology (CIMIT) and
from the Massachusetts Technology Transfer Center
(MTTC). The studies were supported financially by the
Coultier Foundation Translational Research Award.
The authors are grateful to the ARCH staff (Arthur
Nedder, Mark Kelly, Kathryn Mullen, Kimberlie
Hauser) of the Children’s Hospital Boston/Harvard
Medical School for their overwhelming support and
assistance in the project. They also thank Herr Helge
Haselbach, of the Department of Graphics and
Photography of the Deutsches Herzzentrum, Berlin,
Germany.
J Heart Valve Dis
Vol. 20. No. 2
March 2011
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