{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:43:54Z","timestamp":1789494234789,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa Institucional de Bolsas de Inicia\u00e7\u00e3o Cient\u00edfica do Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (PIBIC\/CNPq)","award":["2577\/2020"],"award-info":[{"award-number":["2577\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart dysfunction and liver disease often coexist. Among the types of cardiohepatic syndrome, Type 2 is characterized by the chronic impairment of cardiac function, leading to chronic liver injury, referred to as congestive hepatopathy (CH). In this study, we aimed to establish a rat model of CH secondary to right ventricular hypertrophy (RVH) related to monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Fifty male Wistar rats were divided into four groups and randomly assigned to control and experimental groups. Three experimental groups were submitted to intraperitoneal MCT inoculation (60 mg\/kg) and were under its effect for 15, 30 and 37 days. The animals were then sacrificed, obtaining cardiac and hepatic tissues for anatomopathological and morphometric analysis. At macroscopic examination, the livers in the MCT groups presented a nutmeg-like appearance. PAH produced marked RVH and dilatation in the MCT groups, characterized by a significant increase in right ventricular free wall thickness (RVFWT) and chamber area. At histological evaluation, centrilobular congestion was the earliest manifestation, with preservation of the hepatocytes. Centrilobular hemorrhagic necrosis was observed in the groups exposed to prolonged MCT. Sinusoidal dilatation was markedly increased in the MCT groups, quantified by the Sinusoidal Lumen Ratio (SLR). The Congestive Hepatic Fibrosis Score and the Centrilobular Fibrosis Ratio (CFR) were also significantly increased in the MCT30 group. Hepatic atrophy, steatosis, apoptotic bodies and, rarely, hydropic swelling were also observed. SLR correlated strongly with CFR and RVFWT, and CFR correlated moderately with RVFWT. Our rat model was able to cause CH, related to monocrotaline-induced PAH and RVH; it was feasible, reproducible, and safe.<\/jats:p>","DOI":"10.3390\/ijms222111891","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:39:42Z","timestamp":1635856782000},"page":"11891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9393-2445","authenticated-orcid":false,"given":"Douglas Mesadri","family":"Gewehr","sequence":"first","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"},{"name":"Curitiba Heart Institute, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Fernando","family":"Giovanini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-6060","authenticated-orcid":false,"given":"Beatriz Alvarez","family":"Mattar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelyse Pulner","family":"Agulham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa de Souza","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0069-3823","authenticated-orcid":false,"given":"Seigo","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology of Health and Biological Sciences, Pontifical Catholic University of Paran\u00e1, Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5045-9237","authenticated-orcid":false,"given":"Fernando Bermudez","family":"Kubrusly","sequence":"additional","affiliation":[{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"},{"name":"Curitiba Heart Institute, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6546-9841","authenticated-orcid":false,"given":"Luiz Fernando","family":"Kubrusly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackenzie Evangelical School of Paran\u00e1, Curitiba 80730-000, Brazil"},{"name":"Denton Cooley Institute of Research, Science and Technology, Curitiba 80730-201, Brazil"},{"name":"Curitiba Heart Institute, Curitiba 80730-201, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e578","DOI":"10.1161\/CIR.0000000000000560","article-title":"Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association","volume":"137","author":"Konstam","year":"2018","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s11897-014-0238-0","article-title":"Cardiohepatic Syndrome","volume":"12","author":"Poelzl","year":"2015","journal-title":"Curr. 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