Microsurgically Induced Aneurysm Models in Rats, Part I: Techniques and Histological Examination

Abstract

Introduction: The percentage of aneurysms treated surgically has steadily decreased since the results of the ISAT study were published in 2002. The aim of this study was to develop different reliable and reproducible aneurysm models for microsurgical training and further research to guarantee effective instruction in microsurgery for young neurosurgeons with comparable aneurysms like in humans.

Methods: Arterial and venous pouch aneurysm models were created microsurgically using 22 Wistar rats. The femoral and the proximal iliac vessels and the bifurcation of the common carotid artery were exposed for induction. For histological examination every aneurysm was dissected out and analysed.

Results: A total of 39 microaneurysms was created in three different regions. During the creation four complications occurred: 4 bleedings and 1 defect were observed and immediately treated. Linear regression curves of the microsurgical evaluation showed a significant advancement in the course of the study. The volumes of the different models were: 2.58±1.01 mm³ for the carotid, 6.49±3.36 mm³ for the iliac and 10.41±4.13 mm³ for the femoral aneurysms. The aspect ratios were 1.86±0.45 at the iliac, 1.62±0.3 at the femoral and 1.21±0.29 for the carotid aneurysms. In 89.7% of the cases the aneurysm sac was thrombosed accentuated at the aneurysm tip while the central zone of blood inflow revealed no thrombus formation. The proportion of endothelial cells displayed a reduction in relation to the total number per cross-section in all aneurysm types.

Conclusions: The presented aneurysm models in rats are reliably and immediately available for further training or scientific histological investigations. Despite the fact that these are not bifurcation aneurysms, basic techniques such as suturing and microtechniques used for the dissection and repair of vessels can be taught.

Key words

aneurysm - models - rats - microvascular training

References

• 1 Molyneux A, Kerr R, Stratton I. et al . International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.  Lancet. 2002;  360 1267-1274
• 2 Niemela M, Koivisto T, Kivipelto L. et al . Microsurgical clipping of cerebral aneurysms after the ISAT Study.  Acta Neurochir Suppl. 2005;  94 3-6
• 3 Barker  2nd  FG, Amin-Hanjani S, Butler WE. et al . Age-dependent differences in short-term outcome after surgical or endovascular treatment of unruptured intracranial aneurysms in the United States, 1996-2000.  Neurosurgery. 2004;  54 18-28 , ; discussion 28-30
• 4 Gnanalingham KK, Apostolopoulos V, Barazi S, O’Neill K. The impact of the international subarachnoid aneurysm trial (ISAT) on the management of aneurysmal subarachnoid haemorrhage in a neurosurgical unit in the UK.  Clin Neurol Neurosurg. 2006;  108 117-123
• 5 Johnston SC, Zhao S, Dudley RA, Berman MF, Gress DR. Treatment of unruptured cerebral aneurysms in California.  Stroke. 2001;  32 597-605
• 6 Brouwers PJ, Dippel DW, Vermeulen M. et al . Amount of blood on computed tomography as an independent predictor after aneurysm rupture.  Stroke. 1993;  24 809-814
• 7 Johansson M, Norback O, Gal G. et al . Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage.  Neuroradiology. 2004;  46 385-391
• 8 Vindlacheruvu RR, Dervin JE, Kane PJ. The impact of interventional neuroradiology on neurosurgical training.  Ann R Coll Surg Engl. 2003;  85 3-9
• 9 Britz GW, Newell DW, West GA, Lam A. The ISAT trial.  Lancet. 2003;  361 431-432 , ; author reply 432
• 10 Leung CH, Poon WS, Yu LM. The ISAT trial.  Lancet. 2003;  361 430-431 , ; author reply 432
• 11 Sade B, Mohr G. Critical appraisal of the International Subarachnoid Aneurysm Trial (ISAT).  Neurol India. 2004;  52 32-35
• 12 Aboud E, Al-Mefty O, Yaşargil MG. New laboratory model for neurosurgical training that simulates live surgery.  J Neurosurg. 2002;  97 1367-1372
• 13 Taylor CL, Yuan Z, Selman WR, Ratcheson RA, Rimm AA. Mortality rates, hospital length of stay, and the cost of treating subarachnoid hemorrhage in older patients: institutional and geographical differences.  J Neurosurg. 1997;  86 583-588
• 14 Ujiie H, Tachibana H, Hiramatsu O. et al . Effects of size and shape (aspect ratio) on the hemodynamics of saccular aneurysms: a possible index for surgical treatment of intracranial aneurysms.  Neurosurgery. 1999;  45 119-129 , ; discussion 129-130
• 15 Ujiie H, Tamano Y, Sasaki K, Hori T. Is the aspect ratio a reliable index for predicting the rupture of a saccular aneurysm?.  Neurosurgery. 2001;  48 495-502 , ; discussion 502-503
• 16 Weir B, Amidei C, Kongable G. et al . The aspect ratio (dome/neck) of ruptured and unruptured aneurysms.  J Neurosurg. 2003;  99 447-451
• 17 Maurice-Williams RS, Lafuente J. Intracranial aneurysm surgery and its future.  J R Soc Med. 2003;  96 540-543
• 18 Kirkpatrick PJ, Kirollos RW, Higgins N, Matta B. Lessons to be learnt from the International Subarachnoid Haemorrhage Trial (ISAT).  Br J Neurosurg. 2003;  17 5-7
• 19 Yaşargil MG. Microneurosurgery. New York: Georg Thieme Verlag 1984 1: 5-168
• 20 Yaşargil MG. Microneurosurgery. New York: Georg Thieme Verlag 1984 2: 165-231
• 21 Berman MF, Solomon RA, Mayer SA, Johnston SC, Yung PP. Impact of hospital-related factors on outcome after treatment of cerebral aneurysms.  Stroke. 2003;  34 2200-2207
• 22 Cowan  Jr  JA, Dimick JB, Wainess RM, Upchurch Jr GR, Thompson BG. Outcomes after cerebral aneurysm clip occlusion in the United States: the need for evidence-based hospital referral.  J Neurosurg. 2003;  99 947-952
• 23 Steinberg GK, Ogilvy CS, Shuer LM. et al . Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair.  Neurosurgery. 2004;  55 307-314 , ; discussion 314-305
• 24 Hernesniemi J, Niemela M, Dashti R. et al . Principles of microneurosurgery for safe and fast surgery.  Surg Technol Int. 2006;  15 305-310
• 25 Hernesniemi J, Niemela M, Karatas A. et al . Some collected principles of microneurosurgery: simple and fast, while preserving normal anatomy: a review.  Surg Neurol. 2005;  64 195-200
• 26 Boulos AS, Deshaies EM, Fessler RD. et al . A triple bifurcation aneurysm model for evaluating complex endovascular therapies in dogs.  J Neurosurg. 2005;  103 739-744
• 27 Guglielmi G, Ji C, Massoud TF. et al . Experimental saccular aneurysms. II. A new model in swine.  Neuroradiology. 1994;  36 547-550
• 28 Hoh BL, Rabinov JD, Pryor JC, Ogilvy CS. A modified technique for using elastase to create saccular aneurysms in animals that histologically and hemodynamically resemble aneurysms in human.  Acta Neurochir (Wien). 2004;  146 705-711
• 29 Krings T, Busch C, Sellhaus B. et al . Long-term histological and scanning electron microscopy results of endovascular and operative treatments of experimentally induced aneurysms in the rabbit.  Neurosurgery. 2006;  59 911-923 , ; discussion 923-914
• 30 Krings T, Moller-Hartmann W, Hans FJ. et al . A refined method for creating saccular aneurysms in the rabbit.  Neuroradiology. 2003;  45 423-429
• 31 Miskolczi L, Guterman LR, Flaherty JD, Hopkins LN. Saccular aneurysm induction by elastase digestion of the arterial wall: a new animal model.  Neurosurgery. 1998;  43 595-600 , ; discussion 600-591
• 32 Spetzger U, Reul J, Weis J, Bertalanffy H, Gilsbach JM. Endovascular coil embolization of microsurgically produced experimental bifurcation aneurysms in rabbits.  Surg Neurol. 1998;  49 491-494
• 33 Spetzger U, Reul J, Weis J. et al . Microsurgically produced bifurcation aneurysms in a rabbit model for endovascular coil embolization.  J Neurosurg. 1996;  85 488-495
• 34 Yoshino Y, Niimi Y, Song JK, Silane M, Berenstein A. Endovascular treatment of intracranial aneurysms: comparative evaluation in a terminal bifurcation aneurysm model in dogs.  J Neurosurg. 2004;  101 996-1003
• 35 Kallmes DF, Helm GA, Hudson SB. et al . Histologic evaluation of platinum coil embolization in an aneurysm model in rabbits.  Radiology. 1999;  213 217-222
• 36 Frosen J, Marjamaa J, Myllarniemi M. et al . Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model.  Neurosurgery. 2006;  58 936-944 , ; discussion 936-944
• 37 Vickle-Chavez SJ Van, Tung WS, Absi TS. et al . Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms.  J Vasc Surg. 2006;  43 1010-1020
• 38 Lee D, Yuki I, Murayama Y. et al . Thrombus organization and healing in the swine experimental aneurysm model. Part I. A histological and molecular analysis.  J Neurosurg. 2007;  107 94-108
• 39 Gao YZ, Alphen HA van, Kamphorst W. Observations on experimental saccular aneurysms in the rat after 2 and 3 months.  Neurol Res. 1990;  12 260-263
• 40 Guerreiro NE, Colli BO, Carlotti  Jr  CG, Chimelli L. Experimental microaneurysms in rats: I. Model for induction.  Surg Neurol. 2004;  62 406-412
• 41 Handa H, Hashimoto N, Nagata I, Hazama F. Saccular cerebral aneurysms in rats: a newly developed animal model of the disease.  Stroke. 1983;  14 857-866
• 42 Kirse DJ, Flock S, Teo C, Rahman S, Mrak R. Construction of a vein-pouch aneurysm at a surgically created carotid bifurcation in the rat.  Microsurgery. 1996;  17 681-689
• 43 Thiex R, Moller-Hartmann W, Hans FJ, Scherer K, Krings T. Are the configuration and neck morphology of experimental aneurysms predictable? A technical approach.  Neuroradiology. 2004;  46 571-576
• 44 Szikora I, Seifert P, Hanzely Z. et al . Histopathologic evaluation of aneurysms treated with Guglielmi detachable coils or matrix detachable microcoils.  AJNR Am J Neuroradiol. 2006;  27 283-288
• 45 Weibel ER, Palade GE. New cytoplasmic components in arterial endothelia.  J Cell Biol. 1964;  23 101-112
• 46 Menovsky T. A human skull cast model for training of intracranial microneurosurgical skills.  Microsurgery. 2000;  20 311-313

Correspondence