title: An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel.
abstract: OBJECTIVE
  While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development.
  
  
  METHODS
  The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature.
  
  
  RESULTS
  The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations.
  
  
  CONCLUSIONS
  We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel cross-section and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Antonia E
authors.initials: AE
authors.lastname: Curtin
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Health Information Management, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Leming
authors.initials: L
authors.lastname: Zhou
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D050197:Atherosclerosis / Q000601:surgery*; D003198:Computer Simulation; D003331:Coronary Vessels / Q000601:surgery*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D008670:Metals; D008955:Models, Cardiovascular; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D015203:Reproducibility of Results; D015607:Stents; D013997:Time Factors
chemical_list: D016207:Cytokines; D008670:Metals
references.citation: Chest. 2000 Aug;118(2):503-8
references.pmid: 10936147
references.citation: PLoS One. 2011;6(7):e22683
references.pmid: 21829478
references.citation: Circulation. 2012 Jan 3;125(1):e2-e220
references.pmid: 22179539
references.citation: Int J Clin Exp Pathol. 2010 Jul 25;3(7):643-53
references.pmid: 20830235
references.citation: Chest. 2000 Apr;117(4):1162-72
references.pmid: 10767254
references.citation: Circ Cardiovasc Interv. 2010 Apr;3(2):193-6
references.pmid: 20407116
references.citation: Circulation. 2000 Nov 21;102(21):2582-7
references.pmid: 11085960
references.citation: Biomaterials. 2004 Mar-Apr;25(7-8):1249-59
references.pmid: 14643599
references.citation: Neuroimaging Clin N Am. 2007 Aug;17(3):285-301, vii
references.pmid: 17826632
references.citation: Curr Opin Lipidol. 1999 Dec;10(6):499-506
references.pmid: 10680043
references.citation: Immunology. 2009 Sep;128(1 Suppl):e487-96
references.pmid: 19191907
references.citation: J Clin Invest. 1991 Sep;88(3):904-10
references.pmid: 1832175
references.citation: J Intern Med. 2008 May;263(5):506-16
references.pmid: 18410594
references.citation: Forensic Sci Int. 2010 Dec 15;203(1-3):93-8
references.pmid: 20739128
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):399-404
references.pmid: 14699019
references.citation: Seizure. 2012 Dec;21(10):748-59
references.pmid: 22995680
references.citation: Atherosclerosis. 1996 Feb;120(1-2):221-6
references.pmid: 8645363
references.citation: Nat Rev Drug Discov. 2011 May;10(5):365-76
references.pmid: 21532566
references.citation: Ann Biomed Eng. 2003 Jun;31(6):686-91
references.pmid: 12797618
references.citation: Int J Radiat Biol. 2009 Aug;85(8):690-9
references.pmid: 19637080
references.citation: J Am Coll Cardiol. 1993 Jun;21(7):1557-63
references.pmid: 8496519
references.citation: Int J Cardiol. 2012 Sep 6;159(3):e53-5
references.pmid: 22204849
references.citation: JACC Cardiovasc Interv. 2010 Feb;3(2):191-202
references.pmid: 20170877
references.citation: Semin Immunol. 2008 Apr;20(2):86-100
references.pmid: 18162407
references.citation: FASEB J. 2005 Dec;19(14):1998-2004
references.pmid: 16319143
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):101-5
references.pmid: 8552583
references.citation: Thromb Res. 2000 Sep 1;99(5):461-6
references.pmid: 10973674
references.citation: Eur J Vasc Endovasc Surg. 2007 Jul;34(1):35-43
references.pmid: 17475518
references.citation: Circ J. 2013;77(12):2973-81
references.pmid: 23986083
references.citation: Stroke. 2005 Feb;36(2):367-73
references.pmid: 15625299
references.citation: Circulation. 2000 Sep 5;102(10):1186-91
references.pmid: 10973850
references.citation: Curr Pharm Des. 2011 Dec;17(37):4190-209
references.pmid: 22204378
references.citation: Int J Cardiol. 2013 May 10;165(2):380-2
references.pmid: 22974725
references.citation: Circulation. 2005 May 3;111(17):2257-73
references.pmid: 15867193
references.citation: J Tehran Heart Cent. 2012 Spring;7(2):47-52
references.pmid: 23074637
references.citation: N Engl J Med. 1994 Aug 25;331(8):489-95
references.pmid: 8041413
references.citation: J Am Coll Cardiol. 1992 Feb;19(2):418-32
references.pmid: 1732371
references.citation: Circ Res. 2007 May 11;100(9):1261-75
references.pmid: 17495233
references.citation: PLoS One. 2008 Jul 30;3(7):e2789
references.pmid: 18665229
references.citation: J Clin Invest. 2005 Dec;115(12):3378-84
references.pmid: 16322783
references.citation: Eur J Cardiovasc Med. 2010 Jun;1(2):20-24
references.pmid: 21766004
references.citation: Biotechnol Bioeng. 2007 Aug 1;97(5):1216-29
references.pmid: 17171720
references.citation: PLoS One. 2010 Jan 13;5(1):e8668
references.pmid: 20084270
references.citation: Am J Cardiovasc Drugs. 2013 Aug;13(4):273-83
references.pmid: 23728829
references.citation: Mcgill J Med. 2007 Jul;10(2):105-11
references.pmid: 18523610
references.citation: PLoS One. 2009 Sep 11;4(9):e6990
references.pmid: 19750223
references.citation: Cardiovasc J Afr. 2012 Apr 12;23(3):e9-11
references.pmid: 22555757
references.citation: Am J Cardiol. 2013 Feb 15;111(4):486-92
references.pmid: 23211356
references.citation: Purinergic Signal. 2007 Mar;3(1-2):153-62
references.pmid: 18404429
references.citation: Circulation. 2014 Jan 21;129(3):e28-e292
references.pmid: 24352519
references.citation: J Cell Biol. 1993 Aug;122(3):729-37
references.pmid: 8335696
references.citation: N Engl J Med. 1994 Aug 25;331(8):496-501
references.pmid: 8041414
references.citation: Hypertension. 2005 Oct;46(4):725-31
references.pmid: 16172421
references.citation: J Surg Res. 2011 May 15;167(2):287-97
references.pmid: 21324395
references.citation: Ann Intern Med. 2010 Sep 21;153(6):387-95
references.pmid: 20713770
references.citation: Thrombosis. 2012;2012:608593
references.pmid: 23227328
references.citation: Microbes Infect. 1999 Dec;1(15):1275-82
references.pmid: 10611755
references.citation: J Leukoc Biol. 1999 Jun;65(6):737-43
references.pmid: 10380893
references.citation: Handb Exp Pharmacol. 2005;(170):745-76
references.pmid: 16596822
references.citation: Toxicol Pathol. 2006;34(1):11-8
references.pmid: 16507539
references.citation: Minim Invasive Ther Allied Technol. 2002 Jul;11(4):137-47
references.pmid: 16754063
references.citation: Int J Angiol. 2010 Summer;19(2):e66-72
references.pmid: 22477592
references.citation: Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):309-14
references.pmid: 18079408
references.citation: Am Heart J. 2006 Jun;151(6):1260-4
references.pmid: 16781233
references.citation: Circulation. 1996 Sep 15;94(6):1247-54
references.pmid: 8822976
references.citation: J Am Coll Cardiol. 1992 Aug;20(2):467-74
references.pmid: 1634687
references.citation: Nat Rev Immunol. 2005 Dec;5(12):953-64
references.pmid: 16322748
references.citation: Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1769-76
references.pmid: 12426203
references.citation: Annu Rev Med. 1969;20:47-62
references.pmid: 4894508
references.citation: Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H540-9
references.pmid: 19525370
references.citation: Thromb Res. 2012 Mar;129(3):263-6
references.pmid: 22075180
references.citation: Blood. 2010 Jul 29;116(4):625-7
references.pmid: 20410504
references.citation: Vasc Health Risk Manag. 2005;1(1):73-8
references.pmid: 17319099
references.citation: Math Biosci. 2011 Jun;231(2):186-96
references.pmid: 21385589