Ahmet Kilic, MD, Tieluo Li, MD, Timothy D. C. Nolan, MS, Jennifer R

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Strain-related regional alterations of calcium-handling proteins in myocardial remodeling Ahmet Kilic, MD, Tieluo Li, MD, Timothy D.C. Nolan, MS, Jennifer R. Nash, MS, Shuying Li, MD, Deyanira J. Prastein, MD, Gary Schwartzbauer, PhD, Sina L. Moainie, MD, G. Kwame Yankey, MD, Christopher DeFilippi, MD, Zhongjun Wu, PhD, Bartley P. Griffith, MD The Journal of Thoracic and Cardiovascular Surgery Volume 132, Issue 4, Pages 900-908 (October 2006) DOI: 10.1016/j.jtcvs.2006.07.016 Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Regional end-systolic strain over time. The infarct region shows loss of function immediately post-MI and shows paradoxical dilatation by 2 weeks post-MI. The adjacent region shows a statistically significant systolic dysfunction by 2 weeks post-MI with rapid progression after 6 weeks post-MI. The remote region shows preserved systolic function and a nonstatistically significant trend toward hypercontractility by the time of terminal study. All values are given as mean ± standard error of the mean. *P ≤ .05 as compared with remote region at that time point. †P ≤ .05 as compared with adjacent region at that time point. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 900-908DOI: (10.1016/j.jtcvs.2006.07.016) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Regional end-remodeling strain over time. The infarction region consistently shows the greatest remodeling strain while the adjacent region undergoes a similar remodeling strain, although to a lesser degree than the infarct region. Of note, the greatest increase in end-diastolic strain is observed between 6 weeks post-MI and the time of terminal study. All values are given as mean ± standard error of the mean. *P ≤ .05 as compared with remote region at that time point. †P ≤ .05 as compared with adjacent region at that time point. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 900-908DOI: (10.1016/j.jtcvs.2006.07.016) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Histologic sections of myocardium from the infarct (A, D), adjacent (B, E) and remote (C, F) zones examined with Masson’s trichrome (top) and hematoxylin and eosin (bottom) staining (magnification, ×20). The infarct zone shows marked fibrosis and collagen deposition. The adjacent zone shows lesser degree of fibrosis with myocyte vacuolization visible on hematoxylin-eosin stain. The remote zone has normal, well-preserved myocyte morphology. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 900-908DOI: (10.1016/j.jtcvs.2006.07.016) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 A, Representative Western blots. SERCA2a, Sarcoplasmic reticulum calcium adenosine triphosphatase type 2a; PLB, phospholamban; NCX-1, sodium/calcium exchanger type 1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; N, normal, reference animal; I, infarct zone in MI animal; A, adjacent zone in MI animal; R, remote zone in MI animal. B, Arbitrary density ratio to GAPDH. All values are given as mean ± standard error of the mean. ¥P ≤ .05 as compared with normal, adjacent, and remote tissue. *P ≤ .05 as compared with normal ovine tissue. †P ≤ .05 as compared with remote tissue. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 900-908DOI: (10.1016/j.jtcvs.2006.07.016) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Normalized sarcoplasmic reticulum calcium adenosine triphosphatase type 2a (SERCA2a), phospholamban (PLB), and sodium/calcium exchanger type 1 (NCX-1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plotted as a function of end-systolic strain. A strong negative relationship between SERCA2a (top) and PLB (middle) expression versus end-systolic strain can be observed. A modest positive relationship between NCX-1 (bottom) and end-systolic strain is also observed. At end-systole, the positive strain values indicate lengthening (dilatation) and are seen in the infarct region. Negative strain values correspond with shortening (contraction) and are seen in the adjacent and remote zones. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 900-908DOI: (10.1016/j.jtcvs.2006.07.016) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions