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Technical Brief

Bioengineered Stromal Cell-Derived Factor-1α Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle

[+] Author and Article Information
Alen Trubelja, John W. MacArthur, George Hung, William Hiesinger, Pavan Atluri

Division of Cardiovascular Surgery,
Department of Surgery,
University of Pennsylvania School of Medicine,
Philadelphia, PA 19104

Joseph J. Sarver

School of Biomedical Engineering,
Science & Health Systems,
Drexel University,
Philadelphia, PA 19104

Jeffrey E. Cohen, Yasuhiro Shudo, Jay Patel, Bryan B. Edwards

Department of Cardiothoracic Surgery,
Stanford University School of Medicine,
Stanford, CA 94305

Alexander S. Fairman

Division of Cardiovascular Surgery,
Department of Surgery,
University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Scott M. Damrauer

Division of Vascular Surgery,
Department of Surgery,
University of Pennsylvania School of Medicine,
Philadelphia, PA 19104

Y. Joseph Woo

Department of Cardiothoracic Surgery,
Stanford University School of Medicine,
Stanford, CA 94305
e-mail: joswoo@stanford.edu

Manuscript received December 20, 2013; final manuscript received May 15, 2014; accepted manuscript posted May 23, 2014; published online June 2, 2014. Assoc. Editor: Hai-Chao Han.

J Biomech Eng 136(8), 084501 (Jun 02, 2014) (5 pages) Paper No: BIO-13-1583; doi: 10.1115/1.4027731 History: Received December 20, 2013; Revised May 15, 2014; Accepted May 23, 2014

Ischemic heart disease is a major health problem worldwide, and current therapies fail to address microrevascularization. Previously, our group demonstrated that the sustained release of novel engineered stromal cell-derived factor 1-α analogue (ESA) limits infarct spreading, collagen deposition, improves cardiac function by promoting angiogenesis in the region surrounding the infarct, and restores the tensile properties of infarcted myocardium. In this study, using a well-established rat model of ischemic cardiomyopathy, we describe a novel and innovative method for analyzing the viscoelastic properties of infarcted myocardium. Our results demonstrate that, compared with a saline control group, animals treated with ESA have significantly improved myocardial relaxation rates, while reducing the transition strain, leading to restoration of left ventricular mechanics.

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Figures

Grahic Jump Location
Fig. 1

(a) Representative image of a sham control heart. Specimens were excised from the LV in line from apex to base (white dashed lines). (b) Ventricular biopsies were mounted to an Instron 5543 material testing system. The purple squares indicate the ROIs used for strain analysis.

Grahic Jump Location
Fig. 2

(a) Samples were all preloaded to 0.05 N, at which point gauge length was set. The three incremental stress-relaxation ramps were analyzed to determine the viscoelastic properties of the muscle. (b) The peak and the equilibrium locations of the ramp. (c) The load data for each ramp were normalized using the peak and equilibrium loads in order to calculate the relaxation rate for the last 5% of each cycle. (d) The relaxation rates for each stress-relaxation ramp were analyzed independently for each experimental group. The trend of the ESA treatment group relaxing faster than the saline group is apparent at each increment (p = 0.2165 for the first increment and p = 0.2804 for the second increment). *p = 0.0284 and **p = 0.0065.

Grahic Jump Location
Fig. 3

(a) The bilinear region of the ramp to failure was identified for each specimen and analyzed separately from the linear elastic region. A bilinear curve was fit to the data and used to calculate the break point and transition strain. (b) The difference in the break point between the two best fit lines in the bilinear region was quantified. *p = 0.0110 and **p = 0.0042.

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