Biodegradable elastic patch plasty ameliorates left ventricular adverse remodeling after ischemia–reperfusion injury: A preclinical study of a porous.

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Presentation transcript:

Biodegradable elastic patch plasty ameliorates left ventricular adverse remodeling after ischemia–reperfusion injury: A preclinical study of a porous polyurethane material in a porcine model Ryotaro Hashizume, MD, PhD, Kazuro L. Fujimoto, MD, PhD, Yi Hong, PhD, Jianjun Guan, PhD, Catalin Toma, MD, Kimimasa Tobita, MD, William R. Wagner, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 146, Issue 2, Pages 391-399.e1 (August 2013) DOI: 10.1016/j.jtcvs.2012.11.013 Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Ischemia–reperfusion (I-R) injury and patch implantation protocol. Female swine underwent left circumflex artery (LCx) occlusion for 60 minutes followed by reperfusion (A to D). Black, white, and yellow arrows indicate LCx, occlusion balloon, and completely occluded LCx, respectively. *Left anterior descending (LAD) coronary artery and diagonal branches. The electrocardiogram during the LCx occlusion procedure showed elevated S-T segment and inverted T wave in lead II (D). The study protocol applied is shown in pare E. Circular poly(ester urethane)urea (PEUU) patches were implanted 2 weeks after I-R injury (F). p, Implanted PEUU patch; laa, left atrial appendage; ap, apex of heart. Macroscopic appearance for the PEUU patch implanted heart at the 8-week end point (G). The black dashed line indicates estimated edge of the remnant implanted material. The Journal of Thoracic and Cardiovascular Surgery 2013 146, 391-399.e1DOI: (10.1016/j.jtcvs.2012.11.013) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Macroscopic view of the porous PEUU patch (A) fabricated by thermally induced phase separation. Scanning electron micrograph (B) demonstrates the pore structure of the scaffold. Typical cyclic tensile response curves (C), with a maximum 30% strain, show a lack of obvious unrecoverable scaffold distention after 10 cycles. The Journal of Thoracic and Cardiovascular Surgery 2013 146, 391-399.e1DOI: (10.1016/j.jtcvs.2012.11.013) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Left ventricular wall thickness in the risk zone. Representative photographic images of ventricular transection for the poly(ester urethane)urea (PEUU) patched wall (A) and sham surgery wall (B) at the 8-week time point. The white and yellow arrows represent implanted PEUU patch and suture line for patch implantation, respectively. Epi, Epicardial site; end, endocardial site. Scale bars: 1 cm. The PEUU patched wall (n = 7) was significantly thicker than the sham surgery wall (n = 8) (C). *P < .01. The Journal of Thoracic and Cardiovascular Surgery 2013 146, 391-399.e1DOI: (10.1016/j.jtcvs.2012.11.013) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Hematoxylin and eosin staining and immunostaining for α-smooth muscle actin (αSMA) and CD31. The poly(ester urethane)urea (PEUU) patched wall exhibited an αSMA rich layer (s) beneath the implanted PEUU patch (p). Below the αSMA rich layer was a vascular rich layer (v) and then a myocardial remnant (r) region at the endocardial side (A). epi, Epicardial site; end, endocardial site. *Connective tissue formed above the implanted PEUU. The dashed lines approximate each boundary. Looking at a higher magnification of the boundary area between the PEUU patch and αSMA rich layer showed that the PEUU had partially degraded and cellular infiltration had occurred with αSMA-positive cells (B and C). The junction between αSMA and vascular rich layers is highlighted in (D and E) and the center of the vascular rich layer is showed in parts F and G. The hematoxylin and eosin staining in the MI+sham group is shown in part I. The αSMA-positive structure and vessels in the MI+sham group are shown in part H. Capillary density was greater in the MI-PEUU group than in the MI+sham group (*P < .01) (J). Scale bars: 200 μm. The Journal of Thoracic and Cardiovascular Surgery 2013 146, 391-399.e1DOI: (10.1016/j.jtcvs.2012.11.013) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Temporal echocardiographic assessment for end-diastolic area (EDA) and fractional area change (%FAC) after the patch implantation or sham surgery. Representative M-mode (A and B) and short-axis view of the left ventricle (C and D) at the 8-week time point. Scale bars: 5 cm. The broken lines in parts C and D indicate the inner surface of the left ventricle. The inset in part D shows trivial mitral regurgitation (yellow arrow), a case observed in the MI+sham group. The EDA was significantly greater in the MI+sham than in the MI+PEUU group (E) and %FAC was significantly preserved in the PEUU versus the MI+sham group (n = 7 or 8 for each group) (F). *P < .05 between groups at 8-week time point; †P < .05 versus just before implantation (Pre) within group. The volumetric analysis using estimates derived from left ventricular diameters showed greater increases in left ventricular volume in the MI+sham group at the 8-week point (G and H) and preserved ejection fraction in the MI+PEUU group at 4- and 8-week points (I). LVESV, Left ventricular end-systolic volume; LVEDV, left ventricular end-diastolic volume; ns, not significant. The Journal of Thoracic and Cardiovascular Surgery 2013 146, 391-399.e1DOI: (10.1016/j.jtcvs.2012.11.013) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions