Left ventricular unloading before reperfusion reduces endothelin-1 release and calcium overload in porcine myocardial infarction Sophie Tamareille, PhD,

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Left ventricular unloading before reperfusion reduces endothelin-1 release and calcium overload in porcine myocardial infarction Sophie Tamareille, PhD, Hela Achour, MD, James Amirian, BA, Patricia Felli, BS, Roger J. Bick, PhD, Brian Poindexter, MS, Yong J. Geng, MD, PhD, William H. Barry, MD, Richard W. Smalling, MD, PhD, FACC The Journal of Thoracic and Cardiovascular Surgery Volume 136, Issue 2, Pages 343-351 (August 2008) DOI: 10.1016/j.jtcvs.2008.01.021 Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Bar graph showing infarct size (INF), expressed as a percent of zone at risk (ZR), and zone at risk and infarct zone as a percentage of the LV weight for the LVAD and control groups. Data are expressed as mean ± SEM of 6 independent experiments in each group. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Relationship between infarct size, expressed as a percentage of zone at risk, and collateral blood flow during coronary occlusion in the transmural ischemic zone. By analysis of covariance, a significant reduction in infarct size occurred with unloading, independent of collateral blood flow (P = .025). The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Myocardial ET-1 plasma levels (coronary sinus minus aorta [Cs − Ao]) expressed in picograms per 100 μL in the control and unloaded animals (n = 6 pigs in each group). The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Correlation between myocardial release of ET-1 at 15 minutes of reperfusion and final infarct size. There was a significantly positive correlation between myocardial release of ET-1 and infarct size with an r = 0.79, and a P = .008. CS − AO, Coronary sinus minus aorta. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Effect of LV unloading on ischemia/reperfusion–induced apoptosis in the heart. Apoptotic cardiomyocyte nuclei appear brown-stained, whereas TUNEL-negative nuclei appear blue with hematoxylin and eosin. Heavy staining of numerous TUNEL-positive cardiomyocytes was observed in the central ischemic region of the LV of the sham-operated pig after 1 hour of LAD ischemia and 4 hours of reperfusion. In contrast, few TUNEL-positive cells were detected in the LV ischemic region of the unloaded animal (arrow) (n = 3 to 4 counts for 6 hearts in each group. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Effect of LV unloading on myocardial Ca2+ content. Top, Fluorescence deconvolution images of LV sections (ischemic region) probed with fluo-3 fluorescence. Bottom, Ischemic/nonischemic ratios of fluo-3 fluorescence during occlusion and reperfusion period in control and unloaded animals. Data are expressed as mean ± SEM of 12 to 15 slices of 4 hearts in each group. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 343-351DOI: (10.1016/j.jtcvs.2008.01.021) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions