American Journal of Neuroradiology 26:1764-1767, August 2005
© 2005 American Society of Neuroradiology
Technical Note
INTERVENTIONAL
Creation of Four Experimental Aneurysms with Different Hemodynamics in One Dog
Yong Sam Shina,
Yasunari Niimia,
Yoshikazu Yoshinoa,
Joon K. Songa,
Michael Silanea and
Alejandro Berensteina
a From the Center for Endovascular Surgery, Beth Israel Hyman-Newman Institute for Neurology and Neurosurgery, Roosevelt Hospital, Continuum Health Care Partners, New York, NY
Address reprint requests to Alejandro Berenstein, MD, Center for Endovascular Surgery, Beth Israel Hyman-Newman Institute for Neurology and Neurosurgery, Roosevelt Hospital, Continuum Health Care Partners, 1000 10th Avenue, New York, NY, 10019
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Abstract
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Summary: We developed an experimental canine model in which
four types of aneurysm—bifurcation, side-wall, small branch-artery,
and arterial-stump—were surgically created in the same
animal. These experimental aneurysms are exposed to simultaneous
but different hemodynamic stresses correlating to human intracranial
aneurysms in different locations. Because this model allowed
for the creation of four aneurysms, each with different hemodynamic
features, it seems to offer advantages from ones previously
described. This model may foster investigation of new and current
endovascular devices.
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Introduction
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Improved experimental animal models are needed to evaluate the
safety and efficacy of current and new endovascular devices
to treat intracranial aneurysms. Experimental aneurysms have
been created to simulate various aspects of human intracranial
aneurysms (
1–
5). The use of rabbit experimental aneurysms
is gaining popularity because of its relatively low cost and
the similarity in the sizes of the common carotid artery (CCA)
of the rabbit and the human proximal middle cerebral artery
(
6–
8). However, the rabbit model has limitations, such
as the ability to create only one aneurysm per animal, the high
procedure-related mortality rate, and inadvertent occlusion
of the parent artery (
4,
8). Compared with rabbit models, canine
aneurysms are physiologically more similar to human aneurysms,
more suitable for long-term experiments, and more appropriate
for evaluating human-sized devices (
2,
4,
5,
9,
10). However,
conducting aneurysm experiments in dogs is expensive.
We developed an experimental model in which four aneurysms—bifurcation, side-wall, small branch-artery, and arterial-stump—were created in a single dog in one operation. This canine model can be used as a less-expensive alternative to other models for various animal research and teaching purposes.
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Technique
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Mongrel dogs weighing 16–20 kg were fed standard laboratory
diets before a 12-hour fast before surgery. Anesthesia was induced
with thiopentol 15–20 mg/kg and followed by endotracheal
intubation. Anesthesia was maintained with isoflurane 1%–3%
given through the endotracheal tube. The animals’ necks
and groins were prepared and draped in the usual sterile fashion.
During surgery, the animals’ heart rate, blood pressure,
O
2 saturation, ECG, and depth of anesthesia were monitored.
We describe the surgical procedure in the order in which the
aneurysms were created. All animal experiments were conducted
in accordance with policies set by the Institutional Animal
Care and Use Committee of St. Luke’s/Roosevelt Hospital
Center Animal Care Facility. Institutional approval for the
animal study was required and obtained.
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Arterial-Stump Aneurysm
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A 10-cm midline incision was made in the neck skin. The right
external jugular vein and/or one of its tributaries (anterior
or posterior facial vein) were isolated, and all side branches
were ligated. A 5-cm venous segment was excised by using double-ligation
technique and placed in saline solution containing heparin.
Intraluminal blood in the harvested vein was thoroughly irrigated
with heparinized saline. The venous segment was divided to construct
two or three venous pouches. Both CCAs were then exposed. The
left CCA was twice ligated as proximally as possible, and a
temporary vascular clamp was placed just distal to the ligation.
The artery was then divided between the vascular clamp and ligation
site. The stump of the left CCA was sewn to create an aneurysmal
pouch (
Figs 1 and
2). A short segment of the left CCA could
have been harvested at this time, if an arterial pouch were
needed for later aneurysm creation with an arterial wall.
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FIG 1. Schematic of the four aneurysms surgically created in one dog. A indicates arterial-stump aneurysm; B, bifurcation aneurysm; C, side-wall aneurysm; and D, small branch-artery aneurysm. CTA indicates cranial thyroid artery; SCA, subclavian artery; and VA, vertebral artery.
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FIG 2. Digital subtraction angiogram shows the innominate artery. Left CCA is ligated proximally and divided just above the proximal ligature. Stump of the left CCA is shown as an aneurysmal pouch (asterisk).
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Bifurcation Aneurysm
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The distal segment of the divided left CCA was swung to the
right through a tunnel made behind the trachea. The right CCA
was temporarily closed with temporary clips, and an elliptical
arteriotomy was performed. A partial end-to-side anastomosis
of the left CCA to the proximal arteriotomy of the right CCA
was created by using interrupted monofilament 6–0 Prolene
sutures. One corner of the proximal end of the left CCA was
incised at a variable angle to create the desired size of the
aneurysmal neck. The venous segment from the external jugular
vein or a small arterial pouch taken from the left CCA (
V-shaped
end) was then sutured to the notch formed by the anastomosis
of both CCAs. After the anastomosis was completed, any captured
thrombi were removed through the open-end of the grafted pouch.
The open-end of the grafted vein segment/ arterial pouch was
ligated with 4–0 Prolene sutures to create the bifurcation
aneurysm (
Figs 1 and
3).
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FIG 3. Bifurcation aneurysm is created by using a venous pouch of external jugular vein after a partial end-to-side anastomosis of the left CCA to the proximal part of the arteriotomy of the right CCA. Side-wall aneurysm is created by using a venous pouch of the external jugular vein with slight oblique orientation, and a small branch-artery aneurysm is created by using a venous pouch of the anterior facial vein at the junction of the CCA and cranial thyroid artery (asterisk).
A, Intraoperative view.
B, Digital subtraction image.
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Side-Wall Aneurysm
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After the bifurcation aneurysm was completed, the distal portion
of the right CCA was again temporarily closed with temporary
clips, and an elliptical arteriotomy was created on the lateral
end of the right CCA. The size of the aperture was varied according
to the desired aneurysm size. The venous segment from the external
jugular vein or a small arterial pouch taken from the left CCA
was then sutured to the arteriotomy site. The end of the grafted
aneurysm sac was cut obliquely to decrease risk of possible
spontaneous thrombosis of the aneurysm (
Figs 1 and
3).
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Small Branch-Artery Aneurysm
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The cranial thyroidal artery is a small branch at the distal
portion of CCA (
11). After the right CCA and cranial thyroid
artery were temporarily clipped, a 3–4-mm elliptical incision
was made from the CCA in conjunction with the origin of the
cranial thyroid artery. A small venous pouch (anterior or posterior
facial vein) or arterial pouch was then fitted into the arteriotomy
site (
Figs 1 and
3).
Table 1 summarizes the characteristics
of the four experimental aneurysms.
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Discussion
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An improved in vivo animal model of human intracranial aneurysms
is needed, particularly for academic and industrial evaluations
of the feasibility, safety, and efficacy of current and new
endovascular devices. A robust experimental model should include
the following features: 1) good-quality aneurysms that offer
stability and longevity without spontaneous thrombosis; 2) aneurysmal
homogeneity with hemodynamics, coagulation profiles, and tissue
responses similar to those of human intracranial aneurysms;
3) ease in animal handling and surgical technique; 4) cost-effectiveness;
5) aneurysms that can be treated as human intracranial aneurysms
are; and 6) reproducibility to permit the comparison of devices.
As a laboratory animal, the dog has many of these features, including ease of handling, large vessels for simple surgical technique, and excellent long-term survival (2, 4, 5, 9, 10). However, these animals are expensive, especially when used in large experiments. Therefore, attempts have been made to create multiple aneurysms in a single animal. For example, bilateral side-wall aneurysms and a combination of a bifurcation aneurysm with a side-wall aneurysm have been created in a dog (4, 10). Our multiple-aneurysm model is less expensive than others (Table 2), as four aneurysms—each with different hemodynamic characteristics—were created in one animal.
Modifications for the creation of individual aneurysms are also described. The bifurcation aneurysm from a venous pouch is commonly created in rabbits and dogs (1, 2, 7, 8, 12). Aneurysms of various sizes can be created with this model. We used this model to compare the stability of different coils in aneurysms under hemodynamic stress (13) and to train physicians in endovascular coiling. The replacement of an arterial pouch for a venous pouch in the creation of side-wall and small branch-artery aneurysms was technically feasible. The small branch-artery aneurysm can simulate a small aneurysm, which can be difficult to treat endovascularly because of the incorporation of the parent artery into the neck of the aneurysm. The degree of incorporation of the branch into the neck of the small aneurysm can be surgically controlled. Experimental side-wall aneurysms are prone to spontaneous thrombosis. The incidence of spontaneous thrombosis is determined by the ratio of the volume of the aneurysm to the area of its neck (ostium) (14, 15). To minimize the risk of spontaneous thrombosis in our side-wall aneurysms, an oblique cut was made to maximize ostial area of the aneurysm and to minimize the ratio of aneurysmal volume to ostial area.
We have used this quadruple-aneurysm model in three dogs, with excellent technical results. Although the results are preliminary, spontaneous thrombosis has not occurred in 12 surgically created aneurysms. Giant aneurysms with or without partial thrombosis are difficult to model because a large donor specimen is required and therefore are not covered by this animal model.
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Conclusion
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We created a four-aneurysm canine model that can simulate the
behavior of multiple intracranial aneurysms with different dome,
neck, and hemodynamic characteristics. This model can be used
as an alternative to current canine models in basic research,
device evaluation, and physician training. More experience is
needed to determine its utility.
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Footnotes
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Y.S.S. supported by the postdoctoral fellowship program of the
Korea Science and Engineering Foundation, Seoul, Korea.
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References
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Received September 21, 2004;
accepted after revision October 26, 2004.
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TOP
Abstract
Introduction