Research Papers

A Novel Approach to Assess the In Situ Versus Ex Vivo Mechanical Behaviors of the Coronary Artery

[+] Author and Article Information
Ruoya Wang

George W. Woodruff School of
Mechanical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332

Julia Raykin

Wallace H. Coulter Department
of Biomedical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332

Luke P. Brewster

Parker H. Petit Institute of Bioengineering
and Bioscience,
Georgia Institute of Technology,
Woodruff Memorial Research Building,
101 Woodruff Circle, Suite 5105,
Atlanta, GA 30332;
Department of Surgery,
Emory University School of Medicine,
Atlanta, GA 30307;
Surgical and Research Services,
Atlanta VA Medical Center,
Atlanta, GA 30033
e-mail: lbrewst@emory.edu

Rudolph L. Gleason, Jr.

George W. Woodruff School of
Mechanical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332;
Wallace H. Coulter Department of
Biomedical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332;
Parker H. Petit Institute of Bioengineering
and Bioscience,
Georgia Institute of Technology,
315 Ferst Drive, IBB 2305,
Atlanta, GA 30332
e-mail: rudy.gleason@me.gatech.edu

1Corresponding authors.

2L. P. Brewster and R. L. Gleason, Jr. contributed equally to this work and we would like to acknowledge co-senior authorship.

Manuscript received February 20, 2016; final manuscript received November 12, 2016; published online November 30, 2016. Assoc. Editor: Jonathan Vande Geest.

J Biomech Eng 139(1), 011010 (Nov 30, 2016) (7 pages) Paper No: BIO-16-1067; doi: 10.1115/1.4035262 History: Received February 20, 2016; Revised November 12, 2016

Ex vivo mechanical testing has provided tremendous insight toward prediction of the in vivo mechanical behavior and local mechanical environment of the arterial wall; however, the role of perivascular support on the local mechanical behavior of arteries is not well understood. Here, we present a novel approach for quantifying the impact of the perivascular support on arterial mechanics using intravascular ultrasound (IVUS) on cadaveric porcine hearts. We performed pressure-diameter tests (n = 5) on the left anterior descending coronary arteries (LADCAs) in situ while embedded in their native perivascular environment using IVUS imaging and after removal of the perivascular support of the artery. We then performed standard cylindrical biaxial testing on these vessels ex vivo and compared the results. Removal of the perivascular support resulted in an upward shift of the pressure-diameter curve. Ex vivo testing, however, showed significantly lower circumferential compliance compared to the in situ configuration. On a second set of arteries, local axial stretch ratios were quantified (n = 5) along the length of the arteries. The average in situ axial stretch ratio was 1.28 ± 0.16; however, local axial stretch ratios showed significant variability, ranging from 1.01 to 1.70. Taken together, the data suggest that both the perivascular loading and the axial tethering have an important role in arterial mechanics. Combining nondestructive testing using IVUS with traditional ex vivo cylindrical biaxial testing yields a more comprehensive assessment of the mechanical behavior of arteries.

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Kamenskiy, A. V. , Pipinos, I. I. , Dzenis, Y. A. , Phillips, N. Y. , Desyatova, A. S. , Kitson, J. , Bowen, R. , and MacTaggart, J. N. , 2015, “ Effects of Age on the Physiological and Mechanical Characteristics of Human Femoropopliteal Arteries,” Acta Biomater., 11, pp. 304–313. [CrossRef] [PubMed]
Liu, Y. , Dang, C. , Garcia, M. , Gregersen, H. , and Kassab, G. S. , 2007, “ Surrounding Tissues Affect the Passive Mechanics of the Vessel Wall: Theory and Experiment,” Am. J. Physiol. Heart Circ. Physiol., 293(6), pp. H3290–H3300. [CrossRef] [PubMed]
Liu, Y. , Zhang, W. , and Kassab, G. S. , 2008, “ Effects of Myocardial Constraint on the Passive Mechanical Behaviors of the Coronary Vessel Wall,” Am. J. Physiol. Heart Circ. Physiol., 294(1), pp. H514–H523. [CrossRef] [PubMed]
Steelman, S. M. , Wu, Q. , Wagner, H. P. , Yeh, A. T. , and Humphrey, J. D. , 2010, “ Perivascular Tethering Modulates the Geometry and Biomechanics of Cerebral Arterioles,” J. Biomech., 43(14), pp. 2717–2721. [CrossRef] [PubMed]
Holzapfel, G. , Gasser, T. , and Ogden, R. , 2000, “ A New Constitutive Framework for Arterial Wall Mechanics and a Comparative Study of Material Models,” J. Elasticity Phys. Sci. Solids, 61(1–3), pp. 1–48. [CrossRef]
Humphrey, J. D. , Kang, T. , Sakarda, P. , and Anjanappa, M. , 1993, “ Computer-Aided Vascular Experimentation: A New Electromechanical Test System,” Ann. Biomed. Eng., 21(1), pp. 33–43. [CrossRef] [PubMed]
Wang, R. , Brewster, L. P. , and Gleason, R. L. , 2013, “ In Situ Characterization of the Uncrimping Process of Arterial Collagen Fibers Using Two-Photon Confocal Microscopy and Digital Image Correlation,” J. Biomech., 46(15), pp. 2726–2729. [CrossRef] [PubMed]
Wang, R. , Raykin, J. , Li, H. , Gleason, R. L. , and Brewster, L. P. , 2014, “ Differential Mechanical Response and Microstructural Organization Between Non-Human Primate Femoral and Carotid Arteries,” Biomech. Model. Mechanobiol., 13(5), pp. 1041–1051. [CrossRef] [PubMed]
Talman, A. H. , Psaltis, P. J. , Cameron, J. D. , Meredith, I. T. , Seneviratne, S. K. , and Wong, D. T. L. , 2014, “ Epicardial Adipose Tissue: Far More Than a Fat Depot,” Cardiovasc. Diagn. Ther., 4(6), pp. 416–429. [PubMed]
Wasilewski, J. , Roleder, M. , Niedziela, J. , Nowakowski, A. , Osadnik, T. , Głowacki, J. , Mirota, K. , and Poloński, L. , 2015, “ The Role of Septal Perforators and “Myocardial Bridging Effect” in Atherosclerotic Plaque Distribution in the Coronary Artery Disease,” Pol. J. Radiol., 80, pp. 195–201. [CrossRef] [PubMed]
Bot, I. , de Jager, S. C. A. , Zernecke, A. , Lindstedt, K. A. , van Berkel, T. J. C. , Weber, C. , and Biessen, E. A. L. , 2007, “ Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E-Deficient Mice,” Circulation, 115(19), pp. 2516–2525. [CrossRef] [PubMed]
Robicsek, F. , and Thubrikar, M. J. , 1994, “ The Freedom From Atherosclerosis of Intramyocardial Coronary Arteries: Reduction of Mural Stress: A Key Factor,” Eur. J. Cardiothorac. Surg., 8(5), pp. 228–235. [CrossRef] [PubMed]
Scher, A. M. , 2000, “ Absence of Atherosclerosis in Human Intramyocardial Coronary Arteries: A Neglected Phenomenon,” Atherosclerosis, 149(1), pp. 1–3. [CrossRef] [PubMed]
Verhagen, S. N. , and Visseren, F. L. J. , 2011, “ Perivascular Adipose Tissue as a Cause of Atherosclerosis,” Atherosclerosis, 214(1), pp. 3–10. [CrossRef] [PubMed]
Wang, R. , and Gleason, R. L. , 2010, “ A Mechanical Analysis of Conduit Arteries Accounting for Longitudinal Residual Strains,” Ann. Biomed. Eng., 38(4), pp. 1377–1387. [CrossRef] [PubMed]
Huo, Y. , Cheng, Y. , Zhao, X. , Lu, X. , and Kassab, G. S. , 2012, “ Biaxial Vasoactivity of Porcine Coronary Artery,” Am. J. Physiol. Heart Circ. Physiol., 302(10), pp. H2058–H2063. [CrossRef] [PubMed]
Pandit, A. , Lu, X. , Wang, C. , and Kassab, G. S. , 2005, “ Biaxial Elastic Material Properties of Porcine Coronary Media and Adventitia,” Am. J. Physiol. Heart Circ. Physiol., 288(6), pp. H2581–H2587. [CrossRef] [PubMed]
Zaucha, M. T. , Raykin, J. , Wan, W. , Gauvin, R. , Auger, F. A. , Germain, L. , Michaels, T. E. , and Gleason, R. L. , 2009, “ A Novel Cylindrical Biaxial Computer-Controlled Bioreactor and Biomechanical Testing Device for Vascular Tissue Engineering,” Tissue Eng. Part A, 15(11), pp. 3331–3340. [CrossRef] [PubMed]
Humphrey, J. D. , 2002, Cardiovascular Solid Mechanics: Cells, Tissues, and Organs, Springer, New York.
Weizsacker, H. W. , and Pinto, J. G. , 1988, “ Isotropy and Anisotropy of the Arterial Wall,” J. Biomech., 21(6), pp. 477–487. [CrossRef] [PubMed]
Wang, R. , Raykin, J. , Gleason, R. L. , and Ethier, C. R. , 2015, “ Residual Deformations in Ocular Tissues,” J. R. Soc. Interface, 12(105), p. 20141101. [CrossRef] [PubMed]
Bellamy, R. F. , 1978, “ Diastolic Coronary Artery Pressure-Flow Relations in the Dog,” Circ. Res., 43(1), pp. 92–101. [CrossRef] [PubMed]
Chatterjee, T. K. , Aronow, B. J. , Tong, W. S. , Manka, D. , Tang, Y. , Bogdanov, V. Y. , Unruh, D. , Blomkalns, A. L. , Piegore, M. G. , Weintraub, D. S. , Rudich, S. M. , Kuhel, D. G. , Hui, D. Y. , and Weintraub, N. L. , 2013, “ Human Coronary Artery Perivascular Adipocytes Overexpress Genes Responsible for Regulating Vascular Morphology, Inflammation, and Hemostasis,” Physiol. Genomics 45(16), pp. 697–709. [CrossRef] [PubMed]
Mauro, C. R. , Ilonzo, G. , Nguyen, B. T. , Yu, P. , Tao, M. , Gao, I. , Seidman, M. A. , Nguyen, L. L. , and Ozaki, C. K. , 2013, “ Attenuated Adiposopathy in Perivascular Adipose Tissue Compared With Subcutaneous Human Adipose Tissue,” Am. J. Surg., 206(2), pp. 241–244. [CrossRef] [PubMed]
Rajsheker, S. , Manka, D. , Blomkalns, A. L. , Chatterjee, T. K. , Stoll, L. L. , and Weintraub, N. L. , 2010, “ Crosstalk Between Perivascular Adipose Tissue and Blood Vessels,” Curr. Opin. Pharmacol., 10(2), pp. 191–196. [CrossRef] [PubMed]
Bund, S. J. , Oldham, A. A. , and Heagerty, A. M. , 1996, “ Mechanical Properties of Porcine Small Coronary Arteries in One-Kidney, One-Clip Hypertension,” J. Vasc. Res., 33(2), pp. 175–180. [CrossRef] [PubMed]
Carmines, D. V. , McElhaney, J. H. , and Stack, R. , 1991, “ A Piece-Wise Non-Linear Elastic Stress Expression of Human and Pig Coronary Arteries Tested In Vitro,” J. Biomech., 24(10), pp. 899–906. [CrossRef] [PubMed]
Holzapfel, G. A. , Sommer, G. , Gasser, C. T. , and Regitnig, P. , 2005, “ Determination of Layer-Specific Mechanical Properties of Human Coronary Arteries With Nonatherosclerotic Intimal Thickening and Related Constitutive Modeling,” Am. J. Physiol. Heart Circ. Physiol., 289(5), pp. H2048–H2058. [CrossRef] [PubMed]
Rogowska, J. , Patel, N. A. , Fujimoto, J. G. , and Brezinski, M. E. , 2004, “ Optical Coherence Tomographic Elastography Technique for Measuring Deformation and Strain of Atherosclerotic Tissues,” Heart, 90(5), pp. 556–562. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

(a) A representative cross section of a porcine coronary artery showing the extensive perivascular support surrounding the artery. The artery is subjected to nonuniform perivascular support loading due to different materials primarily adipose tissue and cardiac muscles. This is evident from this image in which the V-shaped stiff cardiac muscle (at the adipose–cardiac muscle interface) appears to be compressing the bottom portion of the artery. (b) and (c) show the method of measuring the local axial stretches that use fiducial markers. (b) The markers are adhered to the artery prior to being dissected out of the heart through a thin incision in the perivascular support. The distances between the ith pair of markers in this configuration are measured as ℓi. (c) The artery is then completely dissected free, and the distances are measured again as Li. The local axial stretch ratios can then be calculated from the ratios of these two measurements.

Grahic Jump Location
Fig. 2

Representative portion of the experimental setup for measuring the pressure-diameter response of the coronary artery in the in situ and partially dissected configurations. Two pressure transducers, P1 and P2, are cannulated and secured between the coronary artery segment of interest. Pressure is provided by a syringe pump (not shown). The IVUS transducer is delivered into the arterial lumen through a one-way port (not shown) and rests in the middle of the dissected segment. A series of ligatures and vascular clips are used to stop outflow from peripheral branches. During testing, the heart is fully submerged in a DPBS bath maintained at physiological temperature (not shown).

Grahic Jump Location
Fig. 3

Measurements of the local axial stretch ratios along the length of the coronary arteries (n = 5). Distance is measured from the bifurcation of the LAD–circumflex coronary artery. Each marker type represents a single coronary artery. Linear regression of the data (black line) yields poor correlation between local stretch ratio and location along the artery (R2 = 0.05).

Grahic Jump Location
Fig. 4

Mean axial stretch ratios calculated using the local stretch measurements for each artery (error bars are mean ± SD). Stretch ratios exhibit significant artery-to-artery variability (*P < 0.05 for artery 2 compared to arteries 1 and 4; #P < 0.01 for artery 5 compared to arteries 1, 3, and 4).

Grahic Jump Location
Fig. 5

Comparison of the pressure-diameter response between the in situ (n = 5; solid line circle markers) and partially dissected (n = 5; dashed line square markers) configurations. A significant increase in diameter was observed in the dissected arteries for pressures between 20 and 60 mm Hg (*P < 0.05; error bars are mean ± SD). Note that diameter data are not available for less than 20 mm Hg due to the arterial wall collapsing around the IVUS transducer.

Grahic Jump Location
Fig. 6

Comparison of compliance-pressure response of ex vivo configuration (dashed line triangle markers) to the in situ (solid line) and partially dissected (dashed line) configurations (error bars are mean ± SD). The partially dissected configuration exhibits higher overall compliance compared to in situ. The ex vivo configuration exhibits the least compliance, demonstrating a critical role of the perivascular support on the mechanical behavior.

Grahic Jump Location
Fig. 7

Representative histological images of the (a) in situ and (b) the ex vivo configurations. Note that the perivascular support in the in situ configuration largely consists of adipocytes. The ex vivo configuration image demonstrates proper removal of the perivascular support, while leaving the arterial wall intact. The lumen is denoted by the letter L, and the black scale bar represents 400 μm.

Grahic Jump Location
Fig. 8

Comparison of the pressure-diameter response of ex vivo configuration (dashed line triangle markers) to the in situ (solid line) and partially dissected (dashed line) configurations (error bars are mean ± SD). The ex vivo pressure-diameter response exhibits appreciable differences, namely, lower compliance between 20 and 80 mm Hg. The ex vivo response exhibits the typical strain-stiffening response at higher pressure.



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