Abstract
Introduction
The purpose of this study was to monitor and to optimize heparinization during endovascular procedures in the New Zealand White Rabbit (NZWR) model.
Methods
Right common carotid artery aneurysms were surgically created in 43 NZWR, with an average weight of 4,330 g (range 3,500–5,430 g). The activated partial thromboplastin time (aPTT) was measured during different stages of the interventional procedures. Blood samples were taken before and 10 min after administration of heparin and at the end of each endovascular procedure. We compared three different experimental groups: 100 U heparin, 500 U heparin and 100 U heparin plus pretreatment with aspirin and clopidogrel. The individual aPTT values were measured using a ball coagulometer.
Results
The average baseline aPTT in the rabbit is 75.2 ± 18.9 s compared to a mean of 33 s (range 26–40 s) in humans. The dosages of heparin used achieved anticoagulation in all cases. Five hundred units of heparin increased the aPTT significantly more than 100 U. No difference was found between the aPTT obtained from the 100 U and the 100 U plus pretreatment group, as aspirin and clopidogrel do not affect the coagulation cascade.
Conclusion
One hundred units of heparin can achieve anticoagulation in a similar magnitude as needed in interventional procedures in humans. This fact enhances suitability of the rabbit animal model for the testing of intravascular devices.
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Abbreviations
- ACT:
-
Acute coagulation time
- ANOVA:
-
Analysis of variance
- aPTT:
-
Activated partial thromboplastin time
- CCA:
-
Common carotid artery
- im:
-
Intramuscular
- ISAT:
-
International Subarachnoid Aneurysm Trial
- NZWR:
-
New Zealand White Rabbit
References
Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, Sandercock P, International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group (2005) International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366(9488):809–817
Raymond J, Salazkin I, Gevry G, Nguyen TN (2007) Interventional neuroradiology: the role of experimental models in scientific progress. AJNR Am J Neuroradiol 28(3):401–405
Grunwald IQ, Papanagiotou P, Politi M, Struffert T, Roth C, Reith W (2006) Endovascular treatment of unruptured intracranial aneurysms: occurrence of thromboembolic events. Neurosurgery 58(4):612–618, discussion 612–8
Naggara O, Darsaut TE, Salazkin I, Soulez G, Guilbert F, Roy D, Weill A, Gevry G, Raymond J (2010) A new canine carotid artery bifurcation aneurysm model for the evaluation of neurovascular devices. AJNR Am J Neuroradiol 31(5):967–971
Dai D, Ding YH, Kadirvel R, Lewis DA, Kallmes DF (2010) Experience with microaneurysm formation at the basilar terminus in the rabbit elastase aneurysm model. AJNR Am J Neuroradiol 31(2):300–303
Killer M, Plenk H, Minnich B, Al-Schameri R, Lametschwantner A, Richling B (2009) Histological demonstration of healing in experimental aneurysms. Minim Invasive Neurosurg 52(4):170–175
Murayama Y, Viñuela F, Suzuki Y, Kaibara M, Kurotobi K, Iwaki M, Abe T (1999) Development of the biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms. Part II: an experimental study in a swine aneurysm model. AJNR Am J Neuroradiol 20(10):1992–1999
Massoud TF, Ji C, Guglielmi G, Viñuela F, Robert J (1994) Experimental models of bifurcation and terminal aneurysms: construction techniques in swine. AJNR Am J Neuroradiol 15:938–944
Guglielmi G, Ji C, Massoud TF, Kurata A, Lownie SP, Viñuela F, Robert J (1994) Experimental saccular aneurysms. II. A new model in swine. Neuroradiology 36:547–550
Turk AS, Aagaard-Kienitz B, Niemann D, Consigny D, Rappe A, Grinde J, Strother CM (2007) Natural history of the canine vein pouch aneurysm model. AJNR Am J Neuroradiol 28:531–532
Dai D, Ding YH, Danielson MA, Kadirvel R, Lewis DA, Cloft HJ, Kallmes DF (2005) Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils. AJNR Am J Neuroradiol 26(10):2560–2568
Raymond J, Berthelet F, Desfaits AC, Salazkin I, Roy D (2002) Cyanoacrylate embolization of experimental aneurysms. AJNR Am J Neuroradiol 23(1):129–138
Byrne JV, Hope JK, Hubbard N, Morris JH (1997) The nature of thrombosis induced by platinum and tungsten coils in saccular aneurysms. AJNR Am J Neuroradiol 18(1):29–33
Carter LP, Guthkelch AN, Orozco J, Temeltas O (1992) Influence of tissue plasminogen activator and heparin on cerebral ischemia in a rabbit model. Stroke 23(6):883–888
Grunwald IQ, Romeike BF, Roth C, Struffert T, Eymann R, Reith W (2005) Anticoagulation regimes and their influence on the occlusion rate of aneurysms: an experimental study in rabbits. Neurosurgery 57(5):1048–1055
Grunwald IQ, Romeike B, Eymann R, Roth C, Struffert T, Reith W (2006) An experimental aneurysm model: a training model for neurointerventionalists. Interv Neuroradiol 12(1):17–24, Epub 2006
Killer M, Kallmes DF, McCoy MR, Ding YH, Shum JC, Cruise GM (2009) Angiographic and histologic comparison of experimental aneurysms embolized with hydrogel filaments. AJNR Am J Neuroradiol 30(8):1488–1495
Ding YH, Dai D, Lewis DA, Danielson MA, Kadirvel R, Cloft HJ, Kallmes DF (2006) Long-term patency of elastase-induced aneurysm model in rabbits. AJNR Am J Neuroradiol 27(1):139–141
Lehman CM, Frank EL (2009) Laboratory monitoring of heparin therapy: partial thromboplastin time or anti-Xa assay. Lab Med 40(1):47–51
Reed SV, Haddon ME, Denson KW (1994) An attempt to standardize the APTT for heparin monitoring, using the P.T. ISI/INR system of calibration. Results of a 13 centre study. Thromb Res 74(5):515–522
Van der Velde EA, Poller L (1995) The APTT monitoring of heparin—the ISTH/ICSH collaborative study. Thromb Haemost 73(1):73–81
Forrest MD, O’Reilly GV (1989) Production of experimental aneurysms at a surgically created arterial bifurcation. AJNR Am J Neuroradiol 10:400–402
Sherif C, Marbacher S, Erhardt S, Fandino J (2011) Improved microsurgical creation of venous pouch arterial bifurcation aneurysms in rabbits. AJNR Am J Neuroradiol 32(1):165–169, Epub 2010
Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G (2004) Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126(3):234–264
Langdell RD, Wagner RH, Brinkhous KM (1953) Effect of anti-hemophilic factor on one-stage clotting test: a presumptive test for hemophilia and a simple one-stage anti-hemophilic factor assay procedure. J Lab Clin Med 41:637–647
Proctor RR, Rapaport SI (1961) The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol 36:212–219
Hoh BL, Rabinov JD, Pryor JC, Ogilvy CS (2004) A modified technique for using elastase to create saccular aneurysms in animals that histologically and hemodynamically resemble aneurysms in human. Acta Neurochir (Wien) 146(7):705–711, Epub 2004
Hussein HM, Georgiadis AL, Qureshi AI (2011) Point-of-care testing for anticoagulation monitoring in neuroendovascular procedures. AJNR Am J Neuroradiol 33(7):1211–1220
Castellan L, Causin F, Danieli D, Perini S (2003) Carotid stenting with filter protection: correlation of ACT values with angiographic and histopathologic findings. J Neuroradiol 30:103–108
Yokote H, Terada T, Ryujin K, Konoshita Y, Tsuura M, Nakai E, Kamei I, Moriwaki H, Hayashi S, Itakura T (1998) Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions. Neuroradiology 40:590–596
Qureshi AI, Suri MF, Siddiqui AM, Kim SH, Boulos AS, Ringer AJ, Lopes DK, Guterman LR, Hopkins LN (2005) Clinical and angiographic results of dilatation procedures for symptomatic intracranial atherosclerotic disease. J Neuroimaging 15:240–249
Gress DR, Smith WS, Dowd CF, Van Halbach V, Finley RJ, Higashida RT (2002) Angioplasty for intracranial symptomatic vertebrobasilar ischemia. Neurosurgery 51:23–27, discussion 27–29
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Schmitt, A.J., Wallner, A.K., Afazel, S. et al. Monitoring of the heparinization in the rabbit animal model during endovascular interventions. Neuroradiology 55, 883–888 (2013). https://doi.org/10.1007/s00234-013-1189-y
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DOI: https://doi.org/10.1007/s00234-013-1189-y