Pharmacological treatment of abdominal aortic aneurysm
DOI:
https://doi.org/10.14739/2310-1210.2013.6.20723Keywords:
abdominal aortic aneurysm, stabilizing therapy, the pathogenesis of the aneurysm, cyclophilin AAbstract
Abdominal aortic aneurysm (AAA) is a common disease with high mortality. Surgical treatment of AAA is performed routinely at a rate of more than 5 cm. Nowadays there isn’t any drug treatment protocol of small aneurysms. Oxidative stress, chronic inflammation in the wall of the abdominal aorta are the fundamental in the pathogenesis of AAA according to the modern literature. Analysis of the literature and our own experience gives opportunity to develop a comprehensive drug therapy of abdominal aortic aneurysms.
Purpose: according to the analysis of the literature and our own research to develop a comprehensive drug therapy of abdominal aortic aneurysms.
Methods.
This study included 48 patients, who were eamined in the Department of Vascular Surgery in Zaporizhzhya Regional Hospital in the period from 2011 to 2013. The middle age was 69.2 ( 54-87 ) years. In 25 cases there were no complaints on the aneurysm, 18 - defined the formation of a pulsating in abdomen. The rest of the complaints were related to the presence of comorbidity. Apart of standard surveys of blood levels of homocysteine Interleukin-6, TNF has been investigated. The basic instrumental methods include: CT imaging of the aorta, coronary angiography.
In this article we analyzed the data of morphological studies of AAA wall, taken at the time of elective making a prosthetic appliance of an AAA. The material was fixed in 10% formalin, embedded in paraffin, sectioned of 4 microns thick. They were stained with hematoxylin - eosin and immunohistochemistry to determine the Cyclophilin A. According to the CT results maximum expansion of the abdominal aorta was 52.27 mm. Coronary angiography was performed in 10 patients, 8 of them had indications for endovascular intervention. Blood tests revealed increasing levels of TNF to 9.83 (7,8-13,9) pg/ml, Interleukin 6 to 5.4 (2-7,46) pg/ml, Homocysteine - 18.39 (11.6 - 29.6) pmol/l.
Elective making a prosthetic appliance of an AAA was performed in 6 patients, in 2 cases we performed endovascular aneurysm repair, other patients (n= 40) were appointed medical (conservative, stabilizing) therapy.
RESULTS
Taking into consideration our morphological study of abdominal aortic aneurysm wall, inflammation and thinning were determined. Intima in many areas was necrotic with attached fragments. Media was thinned, inflammatory changes in the media were in the form of infiltration. Cell infiltrates intensively expressed Cyclophilin A. The main morphological changes in the adventitia were inflammation and fibrosis.
Bruemmer D, Collins AR and others have shown in an experimental model following mechanism for the formation of an aneurysm of the abdominal aorta. Angiotensin II through the induction of oxidative stress stimulates smooth muscle cells Cyclophilin A, which triggers the inflammatory cascade, leading to the destruction of the aortic wall.
On the basis of our observations (the results of examination of patients), analysis of the literature, we have developed a medical (conservative and stabilizing) therapy, designed to stabilize the growth of small aneurysms, the stabilization of large aneurysms (surgery that cannot be due to certain reasons), the prevention of aneurysmal sac rupture after endovascular surgery. A comprehensive treatment including drugs have a direct effect on the pathogenesis of the aneurysm.
References
Suggested standards for reporting on arterial aneurysms. Subcommittee on reporting standards for arterial aneurysms /K.W. Johnston, R.B. Rutherford, M.D. Tilson, D.M. Shah, L. Hollier et al.// Ad Hoc Committee on reporting standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. – J. Vasc.Surg. – 1991. – № 13. –Р. 5452–5819.
McFarlane M.J. The epidemiologic necropsy for abdominal aortic aneurysm / M.J. McFarlane // JAMA. – 1991. – Vol. 265.
– P. 2085–2088.
Cherry aneurysm in the high-risk patient: a plea for abandonment of nonresective treatment /L.H. Hollier, M.M. Reigel, F.J. Kazmier, P.C. Pairolero et al.//JVascSurg. –1991. – Vol. 5. – P. 491–499.
Recommended indications for operative treatment of abdominal aortic aneurysms: report of a subcommittee of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery /L.H. Hollier, L.M. Taylor, J. Oschner// JVascSurg. –1992. – Vol. 15. – P. 1046–1056.
Early elective open surgical repair of small abdominal aortic aneurysms is not recommended: results of the UK Small Aneurysm Trial /R.M. Greenhalgh, J.F. Forbes, F.G. Fowkes, J.T. Powel, C.V. Ruckley, A.R. Brady, L.C. Brown, S.G. Thompson // Eur.J.Vasc.Endovasc.Surg. – 1998. – Vol. 16. – P. 462–464.
Pharmacological treatment of abdominal aortic aneurysm /Takashi Miyake, RyuichiMorishita // Cardiovascular Research. – 2009. – № 83. – Р. 436–443.
Halle JW Jr. Management of abdominal aortic aneurysms /
JW.Jr. Halle // Mayo Clin Proc. – 2000. – № 75. – Р. 395–399.
Is surgery necessary for abdominal aortic aneurysm less than 6 cm in diameter? / R.A. Scott, N.M. Wilson, H.A. Ashton et al. //Lancet. – 1993. – Vol. 342. – P. 1395–1396.
The UK Small Aneurysm Trial Particip ants. Mortality results
for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms // Lancet. – 1998. – № 352. –Р. 1649–1655.
Immediate repair compared with surveillance of small abdominal aortic aneurysms / F.A. Lederle, S.E. Wilson, G.R. Johnson, D.B. Reinke, F.N. Littooy, Acher C.W. et al. // N. Engl. J Med. – 2002. – № 346. – Р. 1437–1444.
Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by measuring the concentration of the aminoterminalpropeptide of type III procollagen in peripheral and aortal blood samples / J. Satta, T. Juvonen, K. Haukipuro, M. Juvonen, M. Kairaluoma // J VascSurg. – 1995. – № 22. –Р. 155–160.
Increased amount of type III pN-collagen in human abdominal aortic aneurysms: evidence for impaired type III collagen fibrillogenesis / M.K. Bode, Y. Soini, J. Melkko, J. Satta, L. Risteli, J. Risteli // JVascSurg. – 2000. – № 32. –Р. 1201–1207.
Elastogenesis in human arterial disease: а role for macrophages in disordered elastin synthesis /A. Krettek, G.K. Sukhova, P. Libby // ArteriosclerThrombVascBiol. – 2003. – № 23. – Р. 582–587.
Oxidative stress in human abdominal aortic aneurysms: a potential mediator of aneurysmal remodeling /F.J. Miller, W.J. Sharp, X. Fang, L.W. Oberley, T.D. Oberley, N.L. Weintraub// ArteriosclerThrombVascBiol.–2002. – № 22. – Р. 560–565.
Reactive oxygen species produced by macrophage derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro / S. Rajagopalan, X.P. Meng, S. Ramasamy, D.G. Harrison, Z.S. Galis // JClinInvest. – 1996. – № 98. – Р. 2572–2579.
Reactive oxygen species induce apoptosis of vascular smooth muscle cell / Li P.F., Dietz R., von Harsdorf R// FEBS Lett. – 1997. – № 404. – Р. 249–252.
Inducible nitric oxide synthase is present in human abdominal aortic aneurysm and promotes oxidative vascular injury /J. Zhang, J. Schmidt, E. Ryschich, M. Mueller-Schilling, H. Schumacher, J.R. Allenberg // JVascSurg. – 2003. – № 38. – Р. 360–367.
Steinmetz EF. Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hyper cholesterolemicmice / EF. Steinmetz, C. Buckley, ML. Shames, TL Ennis, SJ,Mao D.Vanvickle-Cha vezet al // Ann Surg. – 2005. – Vol. 241. – P. 92–101.
Simvastatin suppresses experimental aortic aneurysm expansion / A. Kalyanasundaram, J.R. Elmore, J.R. Manazer, A. Golden, D.P. Franklin, S.W. Galt et al. // JVascSurg. – 2006. – № 43. – Р. 117–124.
Innocent by standard Intraluminal thrombus in abdominal aortic aneurism / K. Yoshimura, Y. Ikeda, H. Aoki // Atherosclerosis. –2011. – № 218. – Р. 285–286.
Is Hypovitaminosis D associated with abdominal aortic aneurysm, and is there adose response relationship / Y.Y.E. Wong, L. Fliker, B.B. Yeap, K.A. McCaul, G.L. Hankey, P.E. Norman // European Journal of Vascular end Endovascular Surgery. – 2013. – V. 45. – № 6. – Р. 656–663.
Decreased Tissue Levels of Ciclophilin A Target and Phospho ERK1/2 in Simvastotin Patients with Abdominal Aortic Aneurysm / A. Piechota-Polanczyk, S. Demyanets, O. Nykonenko, I. Huk,Mittlboek, C.M. Domenik, Neumayer, J. Wojta, J. Nanobachvili, M. Klinger // European Journal of Vascular and Endovascular Surgery. – 2013. – V. 45. – № 6. – Р. 682–688.
A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, cerivastatin, suppresses production of matrix metalloproteinase-9 in human abdominal aortic aneurysm wall / H. Nagashim, Y. Aoka, Y. Sakomura, A. Sakut, S. Aomi, N. Ishizuka et al. // JVascSurg. – 2002. – № 36. – Р. 158–163.
Mortality and size of abdominal aortic aneurysm at long-term follow-up of patients not treated surgically and treated with and without statins /R. Sukhija, W.S. Aronow, R. Sandhu, P. Kakar, S. Babu // AmJCardiol. – 2006. –№ 97. – Р. 279–280.
Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth / O. Schouten, JH. vanLaanen, E. Boersm, R. Vidakovic, HH. Feringa,M. Dunkelgrun et al. // EurJVascEndovascSurg. – 2006. – № 32. –Р. 21–26.
Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors / S. Liao, M. Miralles, B.J. Kelley, J.A. Curci, M. Borhani, R.W. Thompson // JVascSurg. – 2001. – № 33. – Р. 1057–1064.
Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms / L.J. Walton, I.J. Franklin, T. Bayston, L.C. Brown, R.M. Greenhalgh, G.W. Taylor et al // Circulation. – 1999. – № 100. – Р. 48–54.
Selective cyclooxygenase-2 inhibition with celecoxib decreases angiotensin II-induced abdominal aortic aneurysm formation in mice / V.L. King, D.B. Trivedi, J.M. Gitlin, C.D. Loftin // ArteriosclerThrombVascBiol. – 2006. – № 26. – Р. 1137–1143.
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
