{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:16:31Z","timestamp":1793643391477,"version":"4.5.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,3,5]]},"abstract":"\n Background<\/jats:title>\n \n Pulmonary arterial hypertension (\n PAH<\/jats:styled-content>\n ) is a serious disease without cure. Elevated pulmonary vascular resistance puts strain on the right ventricle (\n RV<\/jats:styled-content>\n ) and patients die of\n RV<\/jats:styled-content>\n failure. Subjecting Sprague\u2013Dawley rats to\n SU<\/jats:styled-content>\n 5416 injection and hypoxia promotes severe\n PAH<\/jats:styled-content>\n with pulmonary vascular lesions similar to human disease and has been well utilized to investigate pulmonary vascular pathology. However, despite exhibiting severe\n RV<\/jats:styled-content>\n fibrosis, these rats do not die. Recently, subjecting Fischer (\n CDF<\/jats:styled-content>\n ) rats to the same treatment to promote\n PAH<\/jats:styled-content>\n was found to result in mortality. Thus, the present study performed detailed morphological characterizations of Fischer rats with\n PAH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Rats were subjected to\n SU<\/jats:styled-content>\n 5416 injection and hypoxia for 3\u00a0weeks, followed by maintenance in normoxia. More than 90% of animals died within 6\u00a0weeks of the\n SU<\/jats:styled-content>\n 5416 injection. Necropsy revealed the accumulation of fluid in the chest cavity, right ventricular hypertrophy and dilatation, hepatomegaly, and other indications of congestive heart failure. Time course studies demonstrated the progressive thickening of pulmonary arteries with the formation of concentric lamellae and plexiform lesions as well as\n RV<\/jats:styled-content>\n fibrosis in\n PAH<\/jats:styled-content>\n rats. Transmission electron microscopy demonstrated the destruction of the myofilaments, T\u2010tubules, and sarcoplasmic reticulum.\n RV<\/jats:styled-content>\n mitochondrial damage and fission were found in Fischer rats, but not in Sprague\u2013Dawley rats, with\n PAH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results suggest that the destruction of\n RV<\/jats:styled-content>\n mitochondria plays a role in the mechanism of\n PAH<\/jats:styled-content>\n \u2010induced death. The\n SU<\/jats:styled-content>\n 5416\/hypoxia model in Fischer rats should be useful for further investigating the mechanism of\n RV<\/jats:styled-content>\n failure and finding effective therapeutic agents to increase the survival of\n PAH<\/jats:styled-content>\n patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.011227","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T19:37:46Z","timestamp":1551209866000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Ultrastructural Changes of the Right Ventricular Myocytes in Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"8","author":[{"given":"Nataliia V.","family":"Shults","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Georgetown University Medical Center Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey S.","family":"Kanovka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Georgetown University Medical Center Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Ten Eyck","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Georgetown University Medical Center Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladyslava","family":"Rybka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Georgetown University Medical Center Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro J.","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Georgetown University Medical Center Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.5539\/gjhs.v7n4p307"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-014-0765-4"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00004910"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.03.540"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-5-343"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13167-4"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181e49b83"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00057010"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00072709"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004526"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0343com"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000261658.12024.18"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000520"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00746.2012"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw047"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.883843"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201003-0335OC"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw014"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182551"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0488OC"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.239921"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01605291"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(86)80412-6"},{"key":"e_1_3_1_25_2","first-page":"184","article-title":"Density and composition of mammalian muscle","volume":"9","author":"Mendez J","year":"1961","unstructured":"Mendez J, Keys A. 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