J a n u a r y 2 0 1 0 P a g e | 1 Anthony La Barck Master’s Thesis – Revised Problem Statement Advisor – Tom Merrill Co‐Advisor – Jenn Docimo Committee Members – Smitesh Bakrania, Maria Tahamont, and Krishan Bhatia A Model of Blood Flow during Post‐conditioning Introduction: Post‐conditioning is a therapeutic strategy that aims at preventing lethal reperfusion injury to vital organs, such as the heart and brain1‐3,4. It is performed by cyclically interrupting reperfusion by occluding the blood‐delivering vessel4 with an angioplasty balloon catheter. The balloon periodically inflates and deflates (Figures 1a, 1b, 1c) in the vessel, allowing a less rapid restoration of blood flow to vital organs. a b c Figure 1 – Pictures of angioplasty balloon catheter: 1a)‐fully deflated and approaching occlusion site, 1b)‐partially inflated, and 1c)‐fully inflated, blocking flow in the vessel. The balloon will continue to inflate and deflate based on a user‐specified algorithm. Post‐conditioning studies in animals have shown that its ability to reduce cerebral reperfusion injury depends on the algorithm used1, 5. This algorithm varies the number of occlusion‐reperfusion cycles and the duration of occlusion/reperfusion in each cycle. From these studies, it is likely that the protective mechanisms of post‐conditioning are linked to the fluid mechanics of blood flow. The Problem: The protective mechanisms of post‐conditioning are not well understood2, 4‐6. To our knowledge, the link between blood fluid mechanics and these mechanisms has not been extensively examined. Furthermore, a model that simulates post‐conditioning fluid mechanics currently does not exist. Significance: A blood flow model of post‐conditioning may help explain why different post‐conditioning algorithms vary in effectiveness. This type of model could also be used to help describe the interaction between blood flow and biochemical processes occurring within the body during post‐conditioning. Goal – Create a blood flow model of post‐conditioning in the middle cerebral artery that can describe the fluid behavior during cerebral reperfusion. J a n u a r y 2 0 1 0 P a g e | 2 Plan of Action: I.
Literature Review a. Ischemia/Reperfusion injury b. Postconditioning II.
1‐D Modeling a. Review of fluid dynamic fundamentals (steady pipe flow, Navier‐Stokes equations, etc.) i. Documentation/Reporting b. Study of pulsatile flow i. Basic components of flow (inertia, resistance, capacitance) ii. Lumped analysis 1. Electrical analogy – RLC system models and how each component affects flow 2. MATLAB models (Simulink) of pressure‐flow relations 3. Documentation/Reporting c. Postconditioning model i. Build previous 1‐D to include a specific post‐conditioning algorithm ii. Create pressure/flow plots, compare to available data iii. Documentation/Reporting III.
2‐D Modeling a. Study of middle cerebral artery geometry i. Dimensions, material properties, etc. ii. 2‐D/3‐D artery bifurcation model iii. Documentation/Reporting b. ‘Unlumped’ (differential) analysis i. MATLAB/COMSOL plot of flow/pressure fields ii. Documentation/Reporting c. Postconditioning model i. Develop 2‐D COMSOL model to simulate specific post‐conditioning algorithm in middle cerebral artery ii. Output pressure/flow fields based on postconditioning algorithm 1. Occlusion methods – do solutions differ when methods are varied? iii. Documentation/Reporting IV.
Documentation* a. Thesis compilation *
If time is available after the 2‐D modeling component, the model will be further developed to include thermal and biochemical effects. With these components the model will be used to study the thermal effects of cooled reperfused blood on postconditioning. The model will also demonstrate the biochemical effects by modeling oxygen transport between reperfused blood and ischemic tissue. See Mindmap and Gantt Chart for specific plan of action, containing detailed tasks and dates. J a n u a r y 2 0 1 0 P a g e | 3 References 1. Granfeldt A, Lefer DJ, Vinten‐Johansen J. Protective ischaemia in patients: Preconditioning and postconditioning. Cardiovasc Res 2009 Jul 15;83(2):234‐46. 2. Wang JY, Shen J, Gao Q, Ye ZG, Yang SY, Liang HW, Bruce IC, Luo BY, Xia Q. Ischemic postconditioning protects against global cerebral ischemia/reperfusion‐induced injury in rats. Stroke 2008 Mar;39(3):983‐90. 3. Balakumar P, Rohilla A, Singh M. Pre‐conditioning and postconditioning to limit ischemia‐reperfusion‐
induced myocardial injury: What could be the next footstep? Pharmacol Res 2008 Jun;57(6):403‐12. 4. Gao X, Ren C, Zhao H. Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning. J Neurosci Res 2008 Aug 15;86(11):2505‐11. 5. Xing B, Chen H, Zhang M, Zhao D, Jiang R, Liu X, Zhang S. Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke 2008 Aug;39(8):2362‐9. 6. Hausenloy DJ. Signalling pathways in ischaemic postconditioning. Thromb Haemost 2009 Apr;101(4):626‐34.