A modified rat model of hindlimb ischemia for augmentation and functional measurement of arteriogenesis

Authors

  • Ryan M. McEnaney University of Pittsburgh School of Medicine VA Pittsburgh Healthcare Center
  • Dylan McCreary University of Pittsburgh
  • Edith Tzeng University of Pittsburgh School of Medicine VA Pittsburgh Healthcare Center

DOI:

https://doi.org/10.14440/jbm.2018.234

Keywords:

arteriogenesis, collateral, hindlimb ischemia, imaging

Abstract

Arteriogenesis (collateral artery development) is an adaptive pathway critical for salvage of tissue in the setting of arterial occlusion. Rodent models of arteriogenesis typically involve an experimental occlusion (ligation) of a hindlimb artery and then rely on indirect measures such as laser Doppler perfusion imaging to assess blood flow recovery. Unfortunately, the more commonly utilized measures of distal tissue perfusion at rest are unable to account for hemodynamic and vasoactive variables and thus provide an incomplete assessment of collateral network capacity. We provide a detailed description of modifications to the commonly used model of femoral artery ligation. These serve to alter and then directly assess collateral network’s hemodynamic capacity. By incorporating an arteriovenous fistula distal to the arterial ligation, arterial growth is maximized. Hindlimb perfusion may be isolated to measure minimum resistance of flow around the arterial occlusion, which provides a direct measure of collateral network capacity. Our results reinforce that arteriogenesis is driven by hemodynamic variables, and it can be reliably augmented and measured in absolute terms. Using these modifications to a widely used model, functional arteriogenesis may be more directly studied.

Author Biography

Ryan M. McEnaney, University of Pittsburgh School of Medicine VA Pittsburgh Healthcare Center

Department of Surgery Division of Vascular Surgery Assistant Professor

References

References:

Scholz D, Ziegelhoeffer T, Helisch A, Wagner S, Friedrich C, Podzuweit T, et al. Contribution of arteriogenesis and angiogenesis to postocclusive hindlimb perfusion in mice. J Mol Cell Cardiol. 2002;34:775-87.

Schaper W, Flameng W, Winkler B, Wüsten B, Türschmann W, Neugebauer G, et al. Quantification of collateral resistance in acute and chronic experimental coronary occlusion in the dog. Circulation Research. 1976;39(3):371-7. doi: 10.1161/01.res.39.3.371.

Wang S, Zhang H, Dai X, Sealock R, Faber JE. Genetic architecture underlying variation in extent and remodeling of the collateral circulation. Circ Res. 2010;107(4):558-68. Epub 2010/06/26. doi: 10.1161/circresaha.110.224634. PubMed PMID: 20576932; PubMed Central PMCID: PMCPMC2924933.

Chalothorn D, Faber JE. Strain-dependent variation in collateral circulatory function in mouse hindlimb. Physiol Genomics. 2010;42:469-79.

Schaper W, Scholz D. Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol. 2003;23:1143-51.

Eitenmuller I, Volger O, Kluge A, Troidl K, Barancik M, Cai WJ, et al. The range of adaptation by collateral vessels after femoral artery occlusion. Circ Res. 2006;99(6):656-62. Epub 2006/08/26. doi: 10.1161/01.RES.0000242560.77512.dd. PubMed PMID: 16931799.

Chalothorn D, Clayton J, Zhang H, Pomp D, Faber J. Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains. Physiol Genomics. 2007;30:179-91.

Schwarz JC, van Lier MG, Bakker EN, de Vos J, Spaan JA, VanBavel E, et al. Optimization of Vascular Casting for Three-Dimensional Fluorescence Cryo-Imaging of Collateral Vessels in the Ischemic Rat Hindlimb. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada. 2017;23(1):77-87. Epub 2017/02/24. doi: 10.1017/s1431927617000095. PubMed PMID: 28228173.

Li Y, Choi WJ, Qin W, Baran U, Habenicht LM, Wang RK. Optical coherence tomography based microangiography provides an ability to longitudinally image arteriogenesis in vivo. Journal of neuroscience methods. 2016;274:164-71. Epub 2016/11/05. doi: 10.1016/j.jneumeth.2016.10.010. PubMed PMID: 27751893; PubMed Central PMCID: PMCPmc5116418.

Phillips MR, Moore SM, Shah M, Lee C, Lee YZ, Faber JE, et al. A method for evaluating the murine pulmonary vasculature using micro-computed tomography. The Journal of surgical research. 2017;207:115-22. Epub 2016/12/17. doi: 10.1016/j.jss.2016.08.074. PubMed PMID: 27979466.

Boring YC FU, Jacoby C, Heil M, Schaper W, Schrader J. Lack of ecto-5'-nucleotidase (CD73) promotes arteriogenesis. Cardiovascular Research. 2013;97:88-96.

Jaspers K, Slenter JM, Leiner T, Wagenaar A, Post MJ, Backes WH. Automated multiscale vessel analysis for the quantification of MR angiography of peripheral arteriogenesis. Journal of magnetic resonance imaging : JMRI. 2012;35(2):379-86. Epub 2011/11/03. doi: 10.1002/jmri.22819. PubMed PMID: 22045502.

de Lussanet QG, van Golde JC, Beets-Tan RG, de Haan MW, Zaar DV, Post MJ, et al. Magnetic resonance angiography of collateral vessel growth in a rabbit femoral artery ligation model. NMR in biomedicine. 2006;19(1):77-83. Epub 2006/01/18. doi: 10.1002/nbm.1003. PubMed PMID: 16411251.

Jaspers K, Versluis B, Leiner T, Dijkstra P, Oostendorp M, van Golde JM, et al. MR angiography of collateral arteries in a hind limb ischemia model: comparison between blood pool agent Gadomer and small contrast agent Gd-DTPA. PLoS One. 2011;6(1):e16159. Epub 2011/02/08. doi: 10.1371/journal.pone.0016159. PubMed PMID: 21298092; PubMed Central PMCID: PMCPMC3027628.

Pijls NH, Bech GJ, el Gamal MI, Bonnier HJ, De Bruyne B, Van Gelder B, et al. Quantification of recruitable coronary collateral blood flow in conscious humans and its potential to predict future ischemic events. Journal of the American College of Cardiology. 1995;25(7):1522-8. Epub 1995/06/01. PubMed PMID: 7759702.

Vongsavan N, Matthews B. Some aspects of the use of laser Doppler flow meters for recording tissue blood flow. Experimental physiology. 1993;78(1):1-14. Epub 1993/01/01. PubMed PMID: 8448007.

Schwarz J, van Lier M, Bakker E, de Vos J, Spaan J, VanBavel E, et al. Optimization of vascular casting for three-dimensional fluorescence cryo-imaging of collateral vessels in the ischemic rat hindlimb. Microscopy and Microanalysis. 2017;23:77-87.

van Liebergen RA, Piek JJ, Koch KT, de Winter RJ, Schotborgh CE, Lie KI. Quantification of collateral flow in humans: a comparison of angiographic, electrocardiographic and hemodynamic variables. Journal of the American College of Cardiology. 1999;33(3):670-7. Epub 1999/03/18. PubMed PMID: 10080467.

Bergmann CE, Hoefer IE, Meder B, Roth H, van Royen N, Breit SM. Arteriogenesis depends on circulating monocytes and macrophage accumulation and is severely depressed in op/op mice. J Leukoc Biol. 2006;80:59-65.

Buschmannn I, Heil M, Jost M, Schaper W. Influence of inflammatory cytokines on arteriogenesis. Microcirculation. 2003;10:371-9.

Fung E, Helisch A. Macrophages in collateral arteriogenesis. F Phys. 2012;3:1-11.

Downloads

Published

2018-04-10

How to Cite

1.
McEnaney RM, McCreary D, Tzeng E. A modified rat model of hindlimb ischemia for augmentation and functional measurement of arteriogenesis. J Biol Methods [Internet]. 2018Apr.10 [cited 2022Aug.11];5(2):e89. Available from: https://jbmethods.org/jbm/article/view/234

Issue

Section

Articles

Similar Articles

You may also start an advanced similarity search for this article.