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The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves (<jats:italic>n<\/jats:italic>\u2009=\u200917, 94\u2009\u00b1\u20097\u2009kg), 90\u2009\u03bcm microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end\u2010organ blood flows were quantified with 15\u2010\u03bcm fluorescent\u2010labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte\u2010specific apoptosis were observed. End\u2010organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test <jats:styled-content style=\"fixed-case\">VAD<\/jats:styled-content> and adjunctive biological therapies.<\/jats:p>","DOI":"10.1111\/aor.12129","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T03:11:30Z","timestamp":1374549090000},"source":"Crossref","is-referenced-by-count":17,"title":["Bovine Model of Chronic Ischemic Cardiomyopathy: Implications for Ventricular Assist Device Research"],"prefix":"10.1111","volume":"37","author":[{"given":"Carlo R.","family":"Bartoli","sequence":"first","affiliation":[{"name":"MD\/PhD Program School of Medicine University of Louisville  Louisville KY USA"},{"name":"Cardiovascular Innovation Institute University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie C.","family":"Sherwood","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute University of Louisville  Louisville KY USA"},{"name":"Research Resources Facilities University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guruprasad A.","family":"Giridharan","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute University of Louisville  Louisville KY USA"},{"name":"Department of Bioengineering University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Slaughter","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute University of Louisville  Louisville KY USA"},{"name":"Division of Thoracic and Cardiovascular Surgery University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B.","family":"Wead","sequence":"additional","affiliation":[{"name":"MD\/PhD Program School of Medicine University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumanth D.","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease University of Alabama  Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven C.","family":"Koenig","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute University of Louisville  Louisville KY USA"},{"name":"Department of Bioengineering University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,7,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909938"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.46.3.251"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2004.07.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002480-198907000-00092"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MAT.0000150510.03339.AD"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAT.0b013e3181e7bf3c"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccl.2011.08.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2005.10.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053063"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.933960"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezs320"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2007.12.047"},{"issue":"11","key":"e_1_2_8_14_1","first-page":"I8","article-title":"Hemodynamic and exercise performance with pulsatile and continuous\u2010flow left ventricular assist devices","volume":"116","author":"Haft J","year":"2007","journal-title":"Circulation"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2008.07.032"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2008.06.449"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/758736"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.6.4.521"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9164(00)90016-2"},{"key":"e_1_2_8_20_1","volume-title":"Bulletin AI 8478 (Rev 9\/96)","author":"Health EA","year":"1996"},{"key":"e_1_2_8_21_1","unstructured":"HampshireV.Guidance for Industry and Food and Drug Administration Staff: General Considerations for Animal Studies for Cardiovascular Devices. 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