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Abstract
Introduction To explore the patency and growth of surgical sidewall aneurysms in rabbits.
Materials and methods Forty sidewall aneurysms were created in the right common carotid artery (RCCA). Intravenous digital subtraction angiography (DSA) through the ear vein was performed immediately after creation. Three weeks later, intra-arterial DSA through the femoral artery was performed. Aneurysm sizes (neck, width, height and volume) were measured and calculated immediately after creation and 3 weeks later. Aneurysm patency after creation was evaluated. Differences in aneurysm sizes immediately after creation and 3 weeks later were compared using the Student's t test.
Results Aneurysms and the parent artery remained patent in 38 (95%) of the 40 rabbits 3 weeks after creation. Two other rabbits (5%) showed aneurysm occlusion. There was a significant difference in aneurysm neck size 3 weeks after creation (3.6±0.9 mm vs 2.4±0.4 mm, p<0.0001). The aneurysm became wider 3 weeks later (5.8±1.5 mm vs 4.3±1.2 mm, p<0.0001). Aneurysm length was also larger than immediately after creation (6.1±1.3 mm vs 4.3±1.4 mm, p<0.0001). The aneurysm volume was larger than that created immediately (127.5±89.4 mm3 vs 51.0±34.9 mm3, p<0.0001).
Conclusions The patency rate of sidewall aneurysms in rabbits is high. The aneurysm keeps growing for at least 3 weeks after creation.
- Aneurysm
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Introduction
The sidewall vein pouch aneurysm model was introduced more than 60 years ago1 and is still used in basic and preclinical research, especially for testing of neuroendovascular devices.2–6 The advantage of this model is that its size can be easily controlled by surgery. Reports of spontaneous occlusion of sidewall aneurysms have prevented some studies from using this model.4 However, our experiences indicate that it is possible to achieve high patency of sidewall aneurysms in animals. Furthermore, there is still a demand to use this model in several related research fields, especially for the evaluation of endovascular devices. We performed a study to obtain further insight into the patency rate and size of sidewall aneurysms in rabbits.
Materials and methods
Creation of sidewall aneurysm
Following approval from our Institutional Animal Care and Use Committee, sidewall aneurysms were created in the right common carotid artery (RCCA) in 40 New Zealand white rabbits. Anesthesia was induced by intravenous administration of xylazine (1 mg/kg) and ketamine (10 mg/kg) and was maintained with isoflurane (2–3%) in oxygen (2 l/min). Using sterile technique, an 8 cm paramedian incision was made in the neck. The RCCA and right external jugular vein (REJV) were exposed and dissected. After permanent ligation of the proximal and distal side of the REJV, a 1 cm vein pouch was harvested between the two sides (REJV proximal and distal). A 5 mm arteriotomy of the RCCA was made and temporary ligation was performed to temporarily occlude the proximal and distal sides of the arteriotomy. Heparin (150 units/kg) was injected through the ear vein before anastomosis. An end-to-side anastomosis between the vein pouch and RCCA using an 8-0 Prolene suture was processed. The sidewall aneurysm was created in the RCCA with 90° between the long axis of the aneurysm and parent artery7 by cutting the vein pouch perpendicular to the REJV.
Imaging follow-up
Intravenous digital subtraction angiography (DSA) through the ear vein was performed immediately after creation. Our previous study indicated that intravenous DSA could be used as an alternative imaging method for follow-up of rabbit aneurysms.8 Briefly, 9 ml iodinated contrast material (Omnipaque 300 mg/ml) was injected into the left ear vein catheter at a rate of approximately 2 ml/s during DSA and the x-ray exposure rate was 4 frames/s. Three weeks after creation, intra-arterial DSA through the femoral artery was performed.8
The patency of the aneurysm and the parent artery was evaluated immediately by intravenous DSA and 3 weeks after creation by intra-arterial DSA. The neck size, width and height of the aneurysm were measured and calculated in comparison with external sizing devices from both intravenous and intra-arterial DSA images. The aneurysm volume was calculated using a formula according to the shape of the aneurysm (V=4/3×3.14×(aneurysm width/2)3 for spherical aneurysms and V=4/3×3.14×(aneurysm width/2)2×aneurysm height/2 for ellipsoidal aneurysms). Differences in aneurysm size immediately and 3 weeks after creation were compared using the Student's t test.
Results
Patency of sidewall aneurysms
Aneurysm and the parent artery remained patent in 38 (95%) of the 40 rabbits 3 weeks after creation (figure 1). Two other rabbits (5%) showed aneurysm occlusion by intra-arterial DSA.
(A) Anterior/posterior intravenous digital subtraction angiography (DSA) image immediately after creation showing saccular sidewall aneurysm in right common carotid artery (RCCA) with 90° between the long axis of the aneurysm and parent artery (arrow); widespread spasm of RCCA during vessel separation is also shown (notched right arrow). (B) Intra-arterial DSA image 3 weeks after creation of the aneurysm showing that the aneurysm remains patent (arrow).
Aneurysm neck size
The mean aneurysm neck size was 2.4±0.4 mm immediately after creation and 3.6±0.9 mm 3 weeks after creation, which was significantly larger (p<0.0001).
Aneurysm width
The mean aneurysm width immediately after creation was 4.3±1.2 mm, increasing to 5.8±1.5 mm 3 weeks after creation. This difference was significant (p<0.0001). The aneurysm became wider 3 weeks later.
Aneurysm height
The mean aneurysm height was 4.3±1.4 mm immediately after creation and 6.1±1.3 mm 3 weeks after creation. This difference in aneurysm height was significant (p<0.0001).
Aneurysm volume
Among 38 patent aneurysms in this study, 34 were spherical and 4 were cylindrical in shape. Accordingly, the volumes of these aneurysms were calculated using a different formula to reflect their different shape. The mean aneurysm volume was 51.0±34.9 mm3 immediately after creation and 127.5±89.4 mm3 3 weeks after creation. The aneurysms grew larger with time (p<0.0001; figure 2).
(A) Anterior/posterior intravenous digital subtraction angiography (DSA) image immediately after creation showing a sidewall aneurysm with 90° between the long axis of the aneurysm and parent artery (arrow); vessel spasm is also shown in a long segment of the right common carotid artery (notched right arrow). (B) Intra-arterial DSA image 3 weeks after aneurysm creation showing a larger aneurysm (arrow).
Discussion
Sidewall aneurysms have been used for basic research and for testing endovascular devices for a long time.1–6 When the elastase-induced aneurysm model was introduced it was questioned because its aneurysm wall is a vein pouch instead of an artery wall. In elastase-induced aneurysms, the digested arterial wall mimics the weakened artery wall of human intracranial aneurysms.9 ,10 As a result, the elastase model was developed and has been widely used in recent decades.11 ,12 Another concern regarding sidewall aneurysms is spontaneous occlusion after creation, especially in pigs.4 Thus, the sidewall aneurysm in the pig has almost been abandoned because of the above concerns.13 However, our experiences in both pigs and rabbits indicate that high patency sidewall aneurysms can be made through a deliberate surgical procedure.
Analysis in dogs with large sample numbers indicates that the long-term patency of sidewall aneurysms is excellent.14 In the current study we achieved a 95% patency rate in rabbits. All of these results indicate that the patency of sidewall aneurysms should not be an issue for further research use. In addition, a very long parent artery (the whole CCA) can be used as the loading zone, which is very helpful for deployment of flow diverter devices. The aneurysm size can also be easily controlled by selecting vein pouches of different sizes and making arteriotomies of different shapes. Both sides of the CCA can be used to make sidewall aneurysms, which is especially useful to control for variability in biological responses to implants. This cannot be done in the elastase-induced aneurysm model because only one side of the CCA can be used for aneurysm creation. Other advantages of the rabbit aneurysm model include its low cost, ready availability, reduced ethical concerns and similar characteristics of the thrombotic process to those in humans.15–17 Some researchers have tried to create a bifurcation aneurysm model in rabbits.18 ,19 But, because of the special ‘Y’ shape of the parent artery in that model, it cannot be used to test endovascular devices which require only one parent artery. All these aspects indicate the great value of the sidewall model in rabbits for experimental study.
Researchers have tried to overcome spontaneous occlusion of sidewall aneurysms by designing an oblique angle between the aneurysm long axis and parent artery, which makes the aneurysm shape unparalleled with clinical aneurysms.7 ,20 They found that 100% of sidewall aneurysms occluded automatically when a vertical angle (90°) between the aneurysm long axis and parent artery was used. However, our results in rabbits indicate that 95% of sidewall aneurysms created with an angle of 90° between the aneurysm long axis and parent artery remained patent 3 weeks after creation.
As shown in this study, sidewall aneurysms keep growing up to 3 weeks after creation, which also resembles the intracranial aneurysm and provides evidence that this model is ideal for use in research. In the meantime, it is better for researchers to wait at least 3 weeks after creation when using this model to test endovascular devices which require a relatively stable aneurysm size.
This study is limited by the relatively poor quality of the image of intravenous DSA taken immediately after creation. Intravenous DSA was performed instead of intra-arterial DSA because two sides of the femoral artery were kept for sheath placement for use in further studies (one side for aneurysm treatment and another side for imaging follow-up before sacrifice).
A follow-up time of 3 weeks was selected in this study to observe the patency and growth of the sidewall aneurysm model. Some researchers may feel this time period is not long enough for follow-up, but it has been widely used to evaluate the patency and maturity of both surgical (sidewall and bifurcation) and elastase-induced experimental aneurysms, either for basic research or endovascular device testing.21–25 However, since there are no data in this study after 3 weeks of creation, further study is warranted with special regard to the long-term patency and changes in aneurysm size.
Conclusion
Sidewall aneurysms created in rabbits have a high patency rate and continue to grow up for at least 3 weeks after creation.
References
Footnotes
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Contributors DYH: study conception and design. DYH, TT: acquisition, analysis and interpretation of data. All authors contributed to manuscript drafting, revision for important intellectual content and final approval of the version to be published.
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Funding This work was funded by MicroVention Inc (grant number ANS 1726).
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.