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Granulocyte colony stimulating factor in myocardial infarction with low ejection fraction
Institution:1. Division of Cardiology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, USA;2. CVpath Institute, 19 Firstfield Road, Gaithersburg, MD, USA;3. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, 513 Parnassus Avenue, San Francisco, CA, USA;1. Department of Surgery, Vanderbilt University Medical Center, 1310 24th Avenue South, Nashville, TN 37212, USA;2. Department of Surgery, Nashville Veterans Administration Hospital, 1310 24th Avenue South, Nashville, TN 37212, USA;1. School of International Development, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom;2. School of Environment and Sustainability, Indian Institute for Human Settlements, Bangalore, India;3. Ashoka Trust for Research in Ecology and Environment, Bangalore, India;4. Faculty of Earth and Environmental Science, University for Development Studies, Navrongo, Ghana;5. Department of Geography, History and Environmental Studies, University of Namibia, Windhoek, Namibia;6. Rural Polytechnical Institute for Training and Applied Research (IPR/IFRA), Koulikoro, Mali;7. Institute for Environment and Sanitation Studies (IESS), University of Ghana, Accra, Ghana;1. SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamilnadu, India;2. Department of Biotechnology, School of Bio-engineering, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamilnadu, India;3. Department of Podiatry, Hycare Super Speciality Hospital, MMDA Colony, Arumbakkam, Chennai, 600 106, Tamilnadu, India;1. Department of Chemical Engineering, Isfahan University of Technology, Isfahan, 84156-83111, Iran;2. Danish Hydrocarbon Research and Technology Centre (Centre for Oil and Gas - DTU), Elektrovej 375, DK-2800, Lyngby, Denmark;3. Center for Energy Resources Engineering (CERE), Department of Chemical and Biochemical Engineering, Technical University of Denmark, Denmark;1. Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea;2. Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea;3. Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea;4. R&D Center, Genewel Co., Ltd., Sungnam 13211, South Korea;5. School of Systems Biomedical Science, Soongsil University, Seoul 156-743, South Korea
Abstract:Background: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia–reperfusion with left ventricle ejection fraction of <45% using a clinically relevant dosing and timing regimen. Methods: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 μg/kg at time of reperfusion, followed by SC injections of 5 μg/kg days 5–9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure–volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. Results: GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38 ± 2% vs. 33 ± 2%, p < 0.02) and improved wall motion score index (p < 0.05). Histopathology revealed increased vascular density (p < 0.05) and a trend toward increased areas of viable myocardium compared to control (p = 0.058). Conclusion: GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF (<45%). These results support future clinical trials with GCSF in selected patients with larger MI.
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