Featured Subject: Aneurysms
Endovascular Coil Embolization of Microsurgically Produced Experimental Bifurcation Aneurysms in Rabbits Uwe Spetzger, M.D.,* Ju ¨ rgen Reul, M.D.,† Joachim Weis, M.D.,‡ Helmut Bertalanffy, M.D.,* and Joachim M. Gilsbach, M.D.* *Departments of Neurosurgery, †Neuroradiology, and ‡Neuropathology, Technical University RWTH Aachen, Germany
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– 4.
KEY WORDS
Experimental aneurysm, animal model, coil embolization, subarachnoid hemorrhage.
BACKGROUND
Endovascular treatment of cerebral aneurysms is a relatively new method, since only a few animal models and data are available. The present experimental study was performed in order to establish an appropriate aneurysm animal model, to determine the rate of permanent occlusion, and to correlate radiologic and morphologic findings. METHODS
End-to-side anastomoses of both common carotid arteries were performed microsurgically in 53 chinchilla rabbits. Venous pouches were adapted into the newly created bifurcation, resulting in berry-shaped aneurysms comparable to those in humans with regard to size and hemodynamics. Platinum and tungsten coils were used for endovascular embolization. The embolized aneurysms were investigated radiologically and morphologically. RESULTS
Twenty-three carotid bifurcation aneurysms remained for testing endovascular therapeutic approaches. The morphologic examinations of 13 embolized aneurysms revealed in no instance a complete obliteration, even in the three cases that were considered completely embolized according to angiographic criteria.
ndovascular instrumentation is likely to be established as a generally accepted method in the treatment of cerebral aneurysms. However, little is known about the permanent occlusion rate and long-term results [3,4]. The purpose of this experimental study was to tackle some of the unsettled problems of coil embolization of arterial aneurysms [1]. First, it was necessary to establish an appropriate experimental model of bifurcation aneurysms that resembles the clinical situation in humans as closely as possible [5,7]. The present animal model allows a standardized comparison of the various coil systems and the different coil surface materials, and evaluates the degree of permanent obliteration in aneurysms treated with endovascular coils, according to the radiologic and morphologic findings. These data may ultimately lead to an improvement of the endovascular techniques in the treatment of cerebral aneurysms.
E
CONCLUSIONS
The present animal model is an optimal tool for endovascular research. Analysis of the results of coil obliteration revealed a considerable discrepancy between radiologic and pathologic findings. The radiologic degree of aneurysm occlusion was overestimated. © 1998 by Elsevier Science Inc.
Presented at the 4th International Workshop on Cerebrovascular Surgery, June 11–14, 1995, Chicago, Illinois. Address reprint requests to: Uwe Spetzger, M.D., Department of Neurosurgery, Technical University (RWTH) Aachen, Pauwelsstraße 30, D-52057 Aachen, Germany. Received January 5, 1996; accepted June 7, 1996. © 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Materials and Methods The study was conducted according to current German regulations and guidelines for animal experiments, under approval of the local authorities. Chinchilla rabbits weighing 4 –5 kg were operated under sterile conditions using microsurgical techniques. A midline skin incision was performed, extending from the angle of the mandible to the manubrium sterni. A 1 cm segment of the external jugular vein was resected and kept in heparinized 0090-3019/98/$19.00 PII S0090-3019(96)00437-5
492 Surg Neurol 1998;49:491–4
Spetzger et al
to be complete (. 90% occlusion) or incomplete (, 90% occlusion). The degree of occlusion estimated on the initial DSA was then compared to the final angiographic results. Immediately after the final DSA, the rabbits were killed by perfusion fixation, and gross pathologic examination of the aneurysm was performed. The degree of morphologic obliteration was then evaluated and compared with the angiographic findings (Figure 2A and B).
Results Schematic drawing of a microsurgically performed end-to-side anastomosis of both common carotid arteries. A venous pouch was adapted into the created bifurcation, using interrupted monofilament 10-0 sutures. After removal of the atraumatic vascular clips the axial bloodstream inflated the venous pouch, resulting in a bifurcation aneurysm that closely mimicked human cerebral aneurysms in size and hemodynamics.
1
saline. Both common carotid arteries (CCA) were exposed and isolated. The left CCA was proximally ligated and an atraumatic vascular clip was placed at the distal end to achieve temporary occlusion. The artery was cut obliquely and a V-shaped wedge was resected out of the distal end. Then, the right CCA was proximally and distally closed with atraumatic clips and an elliptical arteriotomy was performed. The bifurcation resulted from an end-toside anastomosis of the left CCA to the proximal part of the arteriotomy of the right CCA, using interrupted monofilament 10-0 sutures (Figure 1). The venous segment was adapted within the remaining aperture of the produced bifurcation. Finally, all clips were removed, then the axial bloodstream abruptly inflated the venous pouch, and a berryshaped bifurcation aneurysm arose. The rabbits were observed daily for general status, respiratory functions, and motor functions. Magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), digital subtraction angiography (DSA), and coil embolization were performed under general anesthesia 3– 4 weeks after surgery. If the bifurcation aneurysm was verified, endovascular occlusion was performed using mechanically detachable tungsten coils (MDC) and electrically detachable platinum coils (GDC). Final DSA was performed either 3 months or 6 months after coil embolization. Three untreated rabbits with documented aneurysms were kept as controls. Angiographic aneurysm obliteration was estimated
Fifty-three animals were operated on and the mean size of the microsurgically produced aneurysms was 5.8 3 4.3 mm (range: 2 3 1 mm–12 3 6.5 mm). Thirteen rabbits (24%) died during the study and were excluded. We had five intraoperative or immediately postoperative deaths due to severe blood loss or anesthetic problems. Another eight animals died or had to be killed in the further course because of infectious complications (three pneumonias; two wound infections) or neurologic deficits (two tetraplegias, one immediately postoperative, one after coil embolization; one trophic disorder and mutilation of the right leg following occlusion of the femoral artery). Ten animals (19%) were excluded from further evaluation, because DSA demonstrated unilateral CCA occlusion, which does not represent the situation of a bifurcation aneurysm as requested. In four aneurysms, coil embolization was not practicable because the aneurysm was less than 2 3 2 mm in size. Three rabbits with demonstrated aneurysms were kept as controls, and follow-up DSA 3 months later showed the aneurysms still patent and completely unchanged in size. The remaining 23 rabbits with bifurcation aneurysms were successfully treated by coil embolization (13 with GDC and 10 with MDC). Immediately after coil embolization, DSA demonstrated five completely occluded aneurysms in the GDC-group and three complete obliterations in the MDC-group. However, final DSA demonstrated three complete occlusions in the group of rabbits embolized with platinum coils and no completely occluded aneurysm treated with tungsten coils. Gross pathologic investigation revealed an incomplete occlusion of all 23 coil embolized bifurcation aneurysms. Recanalization of the aneurysms with open spaces between the coil loops was a consistent finding, and no thrombi were found within the coil basket (Figure 2B).
Endovascular Coil Embolization
Surg Neurol 493 1998;49:491–4
After coil embolization, the radiologic and morphologic findings were compared to determine the degree of permanent aneurysm occlusion. (A) Final DSA 6 months after coil embolization (GDC) demonstrating a microsurgically produced and complete (. 90% occlusion) obliterated bifurcation aneurysm. According to angiographic criteria, this aneurysm was estimated as completely obliterated, because the lumen of the aneurysm appeared totally occluded; however, the aneurysmal neck demonstrated partial recanalization. (B) Gross pathologic examination of this coil embolized bifurcation aneurysm showing an incomplete (, 90% occlusion) obliteration of the aneurysm and a recanalization of the whole aneurysm, without a thrombotic occlusion in between the loops of the coil basket. The microsurgically produced bifurcation was cut longitudinally and the aneurysm is viewed from the neck to the dome.
2
Discussion The aim of surgical and endovascular therapy is to completely exclude the aneurysm from the circulation to prevent regrowth and rebleeding. However, recent evaluations showed that endovascular coil embolization frequently attained only an incomplete obliteration of the orifice of the aneurysm without an endothelialization of the aneurysmal base [6]. Data evaluating the risk of rebleeding in partially occluded aneurysms are not yet available. The present experimental study was designed as a bifurcation aneurysm model to mimic the human condition as closely as possible. Angiographic and color Doppler flow measurements have demonstrated that side-wall aneurysms have a completely different flow pattern within the aneurysmal sac as compared to bifurcation aneurysms. Side-wall aneurysms showed a relatively low flow and often a stasis with consecutive thrombosis [2,8,9]. A major disadvantage of our method was the inevitable long-term care of the animals with a high risk of losing several rabbits due to secondary complications. A general problem of coil embolization is its known instability of coil packing with secondary compaction resulting in recanalization of the ini-
tially occluded lumen. Open spaces and no organized thrombi between the loops of the coil basket were found in all morphologically evaluated aneurysms of our series. We found a general radiologic overestimation of the degree of aneurysmal obliteration. The occlusion was always estimated higher on DSA than actually proven by the gross pathologic investigation. This phenomenon was probably caused by a local X ray extinction of the metal coils. Moreover, the metallic artifacts of the coils could mask the contrast media in recanalized sections of the aneurysmal sac. All these factors make a sufficient estimation of the degree of real aneurysm occlusion in radiologic follow-up more difficult.
Conclusions The proven discrepancy of aneurysmal occlusion as demonstrated in radiologic and morphologic investigations—with an overestimation of the radiologic degree of obliteration—suggest that significant improvements are necessary in the monitoring and therapy of coil embolization of cerebral aneurysms.
494 Surg Neurol 1998;49:491–4
Spetzger et al
The authors thank Prof. Dr. W. Ku¨pper, Dr. K. Scherer, Mr. T. Stopinski, Mrs. C. Fricke, Mr. T. Konert, and Mr. A. Akat for their assistance and valuable support in the care for the animals, and Mrs. Lydia Ahn for the artistic drawing.
9. Strother CM, Graves VB, Rappe A. Aneurysm hemodynamics: an experimental study. AJNR 1993;13:1089 –95.
COMMENTARY
REFERENCES 1. Dawson RC, Krisht AF, Barrow DL, Joseph GJ, Shengelaia GG, Bonner G. Treatment of experimental aneurysms using collagen-coated microcoils. Neurosurgery 1995;36:133– 40. 2. Graves VB, Strother CM, Pratington CR, Rappe AH. Flow dynamics of lateral carotid artery aneurysms and their effects on coils and balloons: an experimental study in dogs. AJNR 1992;13:189 –96. 3. Guglielmi G, Vinuela F, Sepetka I, Macellari V. Electrothrombosis of saccular aneurysms via endovascular approach. Part I. Electrochemical basis, technique, and experimental results. J Neurosurg 1991;75:1–7. 4. Higashida RT, Halbach VV, Dowd CF, Barnwell SL, Hieshima GB. Interventional neurovascular treatment of a giant intracranial aneurysm using platinum microcoils. Surg Neurol 1991;35:64 – 68. 5. Kwan ESK, Heilman CB, Roth PA. Endovascular packing of carotid bifurcation aneurysm with polyester fiber-coated platinum coils in a rabbit model. AJNR 1993;14:323–33. 6. Molyneux AJ, Ellison DW, Morris J, Byrne JV. Histological findings in giant aneurysms treated with Guglielmi detachable coils: report of two cases with autopsy correlation. J Neurosurg 1995;83:129 –32. 7. O’Reilly GV, Utsunomiya R, Rumbaugh CL, Colucci VM. Experimental arterial aneurysms: modification of the production technique. J Microsurg 1981;1:219 –23. 8. Scremin OU, Sonnenschein RR, Rubinstein EH. Cerebrovascular anatomy and blood flow measurements in the rabbit. J Cereb Blood Flow Metab 1982;2:55– 66.
The authors must be congratulated for having developed a nice model of bifurcation aneurysms in rabbits. The animal has coagulation factors close to those of human beings. However, the interpretation of their results is difficult. They have found incomplete occlusion of all of their aneurysms treated with coils, even in the three cases where the angiogram showed complete exclusion of the aneurysm. I find it difficult to extrapolate these results with the treatment of cerebral aneurysms in humans with coils. Also, their results contradict the experimental work done by Michel Mawad that clearly demonstrates that there is a new epithelium that covers the coils at the level of the neck. I wonder whether the explanation of their results depends on the technique they use, without dense packing of the aneurysm. The authors should be encouraged to repeat their experiment after improving the packing of their aneurysms. Gerard Debrun, M.D. Departments of Neurosurgery and Radiology University of Illinois at Chicago Chicago, Illinois
nd so, my fellow Americans: ask not what your country can do for you—ask what you can do for your country.
A
—John F. Kennedy (1961) 35th U.S. President
sk not what your country can do for you, but rather what you can do for your country.
A
—Marcus Tullius Cicero (36 b.c.) Roman orator and statesman