Tomohiro Mizuno, MD, Richard D. Weisel, MD, Ren-Ke Li, MD, PhD

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Reloading the heart: A new animal model of left ventricular assist device removal Tomohiro Mizuno, MD, Richard D. Weisel, MD, Ren-Ke Li, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 130, Issue 1, Pages 99-106 (July 2005) DOI: 10.1016/j.jtcvs.2004.10.002 Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Heterotopic heart transplantation. A, Unloading the heart. The heart and lungs are transplanted into the abdomen of the recipient. The ascending aorta of the donor is anastomosed to the abdominal aorta of the recipient. B, Reloading the heart. The right PA is anastomosed to the distal abdominal aorta of the recipient. The gray arrows indicate coronary flow, the white arrows indicate the blood flow from the abdominal aorta, and the light gray dotted arrows indicate the mixed blood. Asc.Ao, Ascending aorta; Abd.Ao, abdominal aorta; PV, Pulmonary vein; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle; CS, coronary sinus; rt, right; lt, left. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 In this study 49 heart and lung transplantations were performed in total. The second operation was performed on 17 transplanted hearts (RL). Eighteen transplanted hearts were removed 2 weeks after transplantation (UL2). Fourteen transplanted hearts were kept unloaded for a total of 4 weeks (UL4). Eighteen normal hearts (Nor) were also evaluated. Six hearts from each group were used for MMP analysis, and these hearts were not used for left ventricular pressure and volume analysis. W&P, Weight and pressure; LVV, left ventricular volume. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 The pressure traces of the donor LV and the recipient aorta. The left ventricular pressure in the unloaded heart (A) is lower than the recipients’ aortic pressure (A’) but higher in the reloaded heart (B and B’). When the aortic pressure is changed by the level of anesthesia, this tendency remains consistent. In the unloaded heart, the left ventricular pressure is always lower than the recipient’s aortic pressure (C and C’), and in the reloaded heart the left ventricular pressure is always higher than the aortic pressure (D and D’). When the right pulmonary artery is clamped, the LVEDP slowly decreases. When the PA is then unclamped, both LVEDP and the left ventricular systolic pressure slowly increase. AP, Aortic pressure; LV, left ventricle; black arrows, the aortic pressure; white arrows, the left ventricular pressure; rt, right. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 The pressure traces of the donor LV and the recipient aorta. The left ventricular pressure in the unloaded heart (A) is lower than the recipients’ aortic pressure (A’) but higher in the reloaded heart (B and B’). When the aortic pressure is changed by the level of anesthesia, this tendency remains consistent. In the unloaded heart, the left ventricular pressure is always lower than the recipient’s aortic pressure (C and C’), and in the reloaded heart the left ventricular pressure is always higher than the aortic pressure (D and D’). When the right pulmonary artery is clamped, the LVEDP slowly decreases. When the PA is then unclamped, both LVEDP and the left ventricular systolic pressure slowly increase. AP, Aortic pressure; LV, left ventricle; black arrows, the aortic pressure; white arrows, the left ventricular pressure; rt, right. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 LVEDP. After the second operation (RL), the LVEDP increased significantly compared with the LVEDP of the unloaded hearts 2 weeks (UL2) and 4 weeks (UL4) after heart-lung transplantation. *P < .05 compared with UL2. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 A, Photographs of the normal heart (Nor), the unloaded heart (UL2), and the reloaded heart (RL). After unloading, the heart becomes smaller than the normal heart. After reloading, the heart dilates. B, The weight of the LVs decreased significantly 2 weeks after the heart-lung transplantation (UL2) but increased 2 weeks after reloading (RL). C, The left ventricular volume significantly decreased compared with that of the normal heart after unloading (UL2), but 2 weeks after reloading (RL), the left ventricular volume increased again. *P < .05 compared with the left ventricular volume of the normal heart. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 The changes in MMP-9 levels are depicted during the study. Two weeks after the heart transplantation (2 weeks of unloading), MMP-9 levels significantly decreased compared with those of the normal hearts and stayed low, whereas the hearts were kept unloaded for the additional 2 weeks. After the hearts were reloaded, MMP-9 levels increased again. *P < .05 compared with the normal hearts. Nor, The group of normal hearts; UL2, the hearts after 2 weeks of unloading; RL, the hearts reloaded for 2 weeks after 2-week unloading; UL4, the hearts unloaded for 4 weeks. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 99-106DOI: (10.1016/j.jtcvs.2004.10.002) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions