Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension

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 sec...

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Autores principales:	Douglas Mesadri Gewehr, Allan Fernando Giovanini, Beatriz Alvarez Mattar, Anelyse Pulner Agulham, Andressa de Souza Bertoldi, Seigo Nagashima, Fernando Bermudez Kubrusly, Luiz Fernando Kubrusly
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	liver disease congestive hepatopathy hypertrophy right ventricular pulmonary arterial hypertension monocrotaline Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/93b96fa396814dabb356853deba43638
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spelling	oai:doaj.org-article:93b96fa396814dabb356853deba436382021-11-11T17:18:29ZCongestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension10.3390/ijms2221118911422-00671661-6596https://doaj.org/article/93b96fa396814dabb356853deba436382021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11891https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Heart 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 MCT<sub>30</sub> 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.Douglas Mesadri GewehrAllan Fernando GiovaniniBeatriz Alvarez MattarAnelyse Pulner AgulhamAndressa de Souza BertoldiSeigo NagashimaFernando Bermudez KubruslyLuiz Fernando KubruslyMDPI AGarticleliver diseasecongestive hepatopathyhypertrophyright ventricularpulmonary arterial hypertensionmonocrotalineBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11891, p 11891 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver disease congestive hepatopathy hypertrophy right ventricular pulmonary arterial hypertension monocrotaline Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	liver disease congestive hepatopathy hypertrophy right ventricular pulmonary arterial hypertension monocrotaline Biology (General) QH301-705.5 Chemistry QD1-999 Douglas Mesadri Gewehr Allan Fernando Giovanini Beatriz Alvarez Mattar Anelyse Pulner Agulham Andressa de Souza Bertoldi Seigo Nagashima Fernando Bermudez Kubrusly Luiz Fernando Kubrusly Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
description	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 MCT<sub>30</sub> 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.
format	article
author	Douglas Mesadri Gewehr Allan Fernando Giovanini Beatriz Alvarez Mattar Anelyse Pulner Agulham Andressa de Souza Bertoldi Seigo Nagashima Fernando Bermudez Kubrusly Luiz Fernando Kubrusly
author_facet	Douglas Mesadri Gewehr Allan Fernando Giovanini Beatriz Alvarez Mattar Anelyse Pulner Agulham Andressa de Souza Bertoldi Seigo Nagashima Fernando Bermudez Kubrusly Luiz Fernando Kubrusly
author_sort	Douglas Mesadri Gewehr
title	Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
title_short	Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
title_full	Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
title_fullStr	Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
title_full_unstemmed	Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension
title_sort	congestive hepatopathy secondary to right ventricular hypertrophy related to monocrotaline-induced pulmonary arterial hypertension
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/93b96fa396814dabb356853deba43638
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Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension

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