{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:15:20Z","timestamp":1783433720035,"version":"3.54.6"},"reference-count":116,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2008,2,1]],"date-time":"2008-02-01T00:00:00Z","timestamp":1201824000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:p>Recent voluntary withdrawal of the ergoline-derivative Alzheimers\u2019 drug Pergolide (Permax) resulting from demonstrated risk of cardiac valve injury illustrates the increased importance of valve injury in pharmaceutical toxicology. Following the 2001 landmark discovery of cardiac valve injury associated with the widely prescribed anti-obesity drug combination fenfluramine-phentermine, and subsequent withdrawal, the need to understand and assess cardiac valve biology and pathology both preclinically and clinically has been accentuated. Unique aspects of the developmental biology, anatomy, and physiology of cardiac valves compared to main cardiac tissue have been discovered, and key elements of the pathophysiology of various valvular injury mechanisms have been described. Although general clinical cardiac valvular disease in humans has been well characterized, animal modeling of valvular injury has proved to be difficult and undersubscribed. Additionally, both the preclinical, pharmaceutical, toxicologic assessment of valvular injury and the understanding of species-comparative valvular pathology have been limited. As discoveries and awareness grows, the purpose of this paper is to review the structure and function of cardiac valves, mechanisms, and outcomes of the common acquired human cardiac valve diseases, including those that are drug-related; to summarize comparative laboratory animal valvular pathology; and to review the literature of contemporary animal models of valvular injury.<\/jats:p>","DOI":"10.1177\/0192623307312707","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T20:22:19Z","timestamp":1210623739000},"page":"204-217","source":"Crossref","is-referenced-by-count":41,"title":["Cardiac Valvular Pathology: Comparative Pathology and Animal Models of Acquired Cardiac Valvular Diseases"],"prefix":"10.1177","volume":"36","author":[{"given":"Kevin B.","family":"Donnelly","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories, Eli Lilly and Co., Greenfield, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2008,2,1]]},"reference":[{"key":"b1-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.591768"},{"key":"b2-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000255691.76142.4a"},{"key":"b3-0360204","first-page":"797","volume":"13","author":"Aliev G","year":"1998","journal-title":"Histol Histopathol"},{"key":"b4-0360204","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.103.2.521"},{"key":"b5-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000141146.95728.da"},{"key":"b6-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2005.02.001"},{"key":"b7-0360204","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000129842.49926.07"},{"key":"b8-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199208063270602"},{"key":"b9-0360204","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2005.66.1408"},{"key":"b10-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.176857"},{"key":"b11-0360204","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.1.4.523"},{"key":"b12-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00100-4"},{"key":"b13-0360204","volume-title":"Harrison\u2019s Principles of Internal Medicine","author":"Braunwald E","year":"1998"},{"key":"b14-0360204","first-page":"747","volume":"21","author":"Butany J","year":"2005","journal-title":"Can J Cardiol"},{"key":"b15-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2005.09.004"},{"key":"b16-0360204","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600809737"},{"key":"b17-0360204","first-page":"365","volume":"14","author":"Cimini M","year":"2005","journal-title":"J Heart Valve Dis"},{"key":"b18-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708283370901"},{"key":"b19-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.12.070"},{"key":"b20-0360204","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2005.130102.x"},{"key":"b21-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00090-1"},{"key":"b22-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.09.049"},{"key":"b23-0360204","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm263"},{"key":"b24-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-8807(01)00109-0"},{"key":"b25-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.1.1"},{"key":"b26-0360204","doi-asserted-by":"publisher","DOI":"10.1080\/01926230290105703"},{"key":"b27-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2006.08.001"},{"key":"b28-0360204","unstructured":"FDA News2007FDA Announces Voluntary Withdrawal of Pergolide ProductsDrug Industry Daily664from FDA News website:http:\/\/www.fdanews.com\/newsletters"},{"key":"b29-0360204","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0026-895X(24)26444-0","volume":"57","author":"Fitzgerald LW","year":"2000","journal-title":"Mol Pharmacol"},{"key":"b30-0360204","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi248"},{"key":"b31-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907013410101"},{"key":"b32-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.5.1644"},{"key":"b33-0360204","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.13.1703"},{"key":"b34-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000159356.42064.48"},{"key":"b35-0360204","doi-asserted-by":"publisher","DOI":"10.1007\/BF00263958"},{"key":"b36-0360204","first-page":"62","volume":"114","author":"Hauck AJ","year":"1990","journal-title":"Arch Pathol Lab Med"},{"key":"b37-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2007.02.009"},{"key":"b38-0360204","first-page":"235","volume":"5","author":"Hendrikx M","year":"1996","journal-title":"J Heart Valve Dis"},{"key":"b39-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000224114.65109.4e"},{"key":"b40-0360204","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200603000-00005"},{"key":"b41-0360204","doi-asserted-by":"publisher","DOI":"10.1002\/clc.4960280303"},{"key":"b42-0360204","doi-asserted-by":"publisher","DOI":"10.1177\/019262338901700112"},{"key":"b43-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64489-6"},{"key":"b44-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391102"},{"key":"b45-0360204","doi-asserted-by":"publisher","DOI":"10.1038\/ng0303-331"},{"key":"b46-0360204","doi-asserted-by":"publisher","DOI":"10.1080\/01926230500369915"},{"key":"b47-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391101"},{"key":"b48-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.20.2345"},{"key":"b49-0360204","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-003-0751-0"},{"key":"b50-0360204","doi-asserted-by":"publisher","DOI":"10.1385\/CRIAI:23:3:341"},{"key":"b51-0360204","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1924.00110300044002"},{"key":"b52-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.3.368"},{"key":"b53-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)01435-7"},{"key":"b54-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-8807(01)00102-8"},{"key":"b55-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-8807(02)00110-2"},{"key":"b56-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.554667"},{"key":"b57-0360204","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1994.1102"},{"key":"b58-0360204","first-page":"1075","volume":"55","author":"MMWR","year":"2006","journal-title":"Morbidity and Mortality Weekly Report"},{"key":"b59-0360204","volume-title":"Pathobiology of the Aging Rat","author":"Mohr U","year":"1992"},{"key":"b60-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021451"},{"key":"b61-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(92)90233-S"},{"key":"b62-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2005.01.003"},{"key":"b63-0360204","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422715"},{"key":"b64-0360204","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2006.00441.x"},{"key":"b65-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907153410302"},{"key":"b66-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62520-5"},{"key":"b67-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00113-9"},{"key":"b68-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200511033531822"},{"key":"b69-0360204","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.6.4072-4078.2001"},{"key":"b70-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/hc4601.099489"},{"key":"b71-0360204","first-page":"215","volume":"56","author":"Rafel Ribera J","year":"2003","journal-title":"Rev Esp Cardiol"},{"key":"b72-0360204","first-page":"827","volume":"10","author":"Rajamannan NM","year":"2001","journal-title":"J Heart Valv Dis"},{"key":"b73-0360204","first-page":"371","volume":"10","author":"Rajamannan NM","year":"2001","journal-title":"J Heart Valve Dis"},{"key":"b74-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000070591.21548.69"},{"key":"b75-0360204","first-page":"99","volume":"27","author":"Raman S","year":"2003","journal-title":"Curr Prob Cardiol"},{"key":"b76-0360204","doi-asserted-by":"publisher","DOI":"10.1081\/DCT-100100126"},{"key":"b77-0360204","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-1-50"},{"key":"b78-0360204","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.44.6.621"},{"key":"b79-0360204","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000807"},{"key":"b80-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198311173092007"},{"key":"b81-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.23.2836"},{"key":"b82-0360204","volume-title":"Nonproliferative lesions in the heart and vasculature in rats","author":"Ruben Z","year":"2000"},{"key":"b83-0360204","volume-title":"Acquired Valvular Diseases","author":"Rubin G","year":"1992"},{"key":"b84-0360204","first-page":"1","volume-title":"Proceedings of the 26th Annual Waltham Diets\/OSU Symposium for the Treatment of Small Animal Cardiology","author":"Rush JE","year":"2002"},{"key":"b85-0360204","volume-title":"Comprehensive Toxicology","volume":"6","author":"Sandusky GE","year":"1997"},{"key":"b86-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062222"},{"key":"b87-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0232-1513(11)80340-3"},{"key":"b88-0360204","first-page":"1","volume":"6","author":"Schoen FJ","year":"1997","journal-title":"J Heart Valve Dis"},{"key":"b89-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2005.03.005"},{"key":"b90-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2006.05.001"},{"key":"b91-0360204","first-page":"402","volume-title":"Cardiovascular Pathology","author":"Schoen FJ","year":"2001"},{"key":"b92-0360204","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0456-5"},{"key":"b93-0360204","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200209000-00007"},{"key":"b94-0360204","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4543"},{"key":"b95-0360204","doi-asserted-by":"publisher","DOI":"10.1097\/00045415-200211000-00005"},{"key":"b96-0360204","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.6.1223"},{"key":"b97-0360204","first-page":"443","volume-title":"Cardiovascular Pathology","author":"Silver MD","year":"2001"},{"key":"b98-0360204","doi-asserted-by":"publisher","DOI":"10.1136\/heart.83.6.721"},{"key":"b99-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-8807(99)00019-8"},{"key":"b100-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(96)00563-3"},{"key":"b101-0360204","volume-title":"Harrison\u2019s Principles of Internal Medicine","author":"Stollerman GH","year":"1995","edition":"13"},{"key":"b102-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.03.058"},{"key":"b103-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00100-0"},{"key":"b104-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2006.04.007"},{"key":"b105-0360204","first-page":"1489","volume":"16","author":"Veinot JP","year":"2000","journal-title":"Can J Cardiol"},{"key":"b106-0360204","doi-asserted-by":"publisher","DOI":"10.5858\/2001-125-1555-AAMFPV"},{"key":"b107-0360204","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1998.tb00350.x"},{"key":"b108-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000136520.07995.aa"},{"key":"b109-0360204","doi-asserted-by":"publisher","DOI":"10.1385\/COMP:32:2:94"},{"key":"b110-0360204","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.634139"},{"key":"b111-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391103"},{"key":"b112-0360204","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23701"},{"key":"b113-0360204","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64497-5"},{"key":"b114-0360204","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100004650"},{"key":"b115-0360204","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054830"},{"key":"b116-0360204","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11226"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623307312707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623307312707","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623307312707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:29:50Z","timestamp":1777652990000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623307312707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2]]},"references-count":116,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,2]]}},"alternative-id":["10.1177\/0192623307312707"],"URL":"https:\/\/doi.org\/10.1177\/0192623307312707","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2]]}}}