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PRECLINICAL STUDY

An Elastic, Biodegradable Cardiac Patch Induces Contractile Smooth Muscle and Improves Cardiac Remodeling and Function in Subacute Myocardial Infarction

Kazuro L. Fujimoto, MD^_*,, Kimimasa Tobita, MD^,,, W. David Merryman, PhD, Jianjun Guan, PhD^_*,, Nobuo Momoi, MD, PhD, Donna B. Stolz, PhD^||, Michael S. Sacks, PhD^,, Bradley B. Keller, MD^,,|| and William R. Wagner, PhD^_*,,,_*

^_* Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania
Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania
^|| Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Manuscript received October 23, 2006; revised manuscript received January 31, 2007, accepted February 18, 2007.

^_* Reprint requests and correspondence: Dr. William R. Wagner, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219. (Email: wagnerwr{at}upmc.edu).

Objectives: Our objective in this study was to apply an elastic, biodegradable polyester urethane urea (PEUU) cardiac patch onto subacute infarcts and to examine the resulting cardiac ventricular remodeling and performance.

Background: Myocardial infarction induces loss of contractile mass and scar formation resulting in adverse left ventricular (LV) remodeling and subsequent severe dysfunction.

Methods: Lewis rats underwent proximal left coronary ligation. Two weeks after coronary ligation, a 6-mm diameter microporous PEUU patch was implanted directly on the infarcted LV wall surface (PEUU patch group, n = 14). Sham surgery was performed as an infarction control (n = 12). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 8 weeks after patch implantation.

Results: The end-diastolic LV cavity area (EDA) did not change, and the fractional area change (FAC) increased in the PEUU patch group (p < 0.05 vs. week 0), while EDA increased and FAC decreased in the infarction control group (p < 0.05). The PEUU patch was largely resorbed 8 weeks after implantation and the LV wall was thicker than infarction control (p < 0.05 vs. control group). Abundant smooth muscle bundles with mature contractile phenotype were found in the infarcted myocardium of the PEUU group. The myocardial compliance of the PEUU group was distributed between normal myocardium and infarction control (p < 0.001).

Conclusions: Implantation of a novel biodegradable PEUU patch onto a subacute myocardial infarction promoted contractile phenotype smooth muscle tissue formation and improved cardiac remodeling and contractile function at the chronic stage. Our findings suggest a new therapeutic option against post-infarct cardiac failure.

Abbreviations and Acronyms   bFGF = basic fibroblast growth factor   CHF = congestive heart failure   EDA = end-diastolic left ventricular cavity area   ESA = end-systolic left ventricular cavity area   FAC = fractional area change   LV = left ventricular   PEUU = polyester urethane urea   P-E = pressure-strain   SMA = smooth muscle actin   SMMHC-2 = smooth muscle myosin heavy chain 2   VEGF = vascular endothelial growth factor