Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion
<b>Background/Objectives:</b> Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although me...
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2024-11-01
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| author | Hezio Jadir Fernandes Junior Erisvaldo Amarante de Araújo José Antônio Machado Junior Fabio Marinho Lutz Motta Gabriela Ferrazzano Guarize Lucas Chen Cheng Junaid Tantray Jand Venes Rolim Medeiros Lucas Antonio Duarte Nicolau Adriano Henrique Pereira Barbosa Adriano Caixeta Isadora S. Rocco Solange Guizilini Marcelo Pires-Oliveira Murched Omar Taha Afonso Caricati-Neto Walter José Gomes Fernando Sabia Tallo Francisco Sandro Menezes-Rodrigues |
| author_facet | Hezio Jadir Fernandes Junior Erisvaldo Amarante de Araújo José Antônio Machado Junior Fabio Marinho Lutz Motta Gabriela Ferrazzano Guarize Lucas Chen Cheng Junaid Tantray Jand Venes Rolim Medeiros Lucas Antonio Duarte Nicolau Adriano Henrique Pereira Barbosa Adriano Caixeta Isadora S. Rocco Solange Guizilini Marcelo Pires-Oliveira Murched Omar Taha Afonso Caricati-Neto Walter José Gomes Fernando Sabia Tallo Francisco Sandro Menezes-Rodrigues |
| author_sort | Hezio Jadir Fernandes Junior |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB’s effects on the heart are unclear. Therefore, we investigated the potential cardioprotective or arrhythmogenic effects of MB in an animal model of CIR. To this end, 12–16-week-old male Wistar rats were divided into four experimental groups: (a) rats subjected to SHAM surgery with no ischemia; (b) rats subjected to CIR and treated with a vehicle (SS + CIR); and (c) rats subjected to CIR and treated with 2 mg/kg i.v. MB before ischemia (MB + ISQ) or (d) after ischemia but before reperfusion (ISQ + MB). An ECG analysis was used to evaluate the incidence of ventricular arrhythmias (VAs), atrioventricular blocks (AVBs), and lethality (LET) resulting from CIR. After CIR, rat hearts were removed for histopathological analysis and lipid hydroperoxide (LH) measurements. <b>Results:</b> The incidence of VA, AVB, and LET was significantly increased in the MB + ISQ group (VA = 100%; AVB = 100%; LET = 100%) but significantly reduced in the ISQ + MB group (VA = 42.8%; AVB = 28.5%; LET = 21.4%) compared with the SS + CIR group (VA = 85.7%; AVB = 71.4%; LET = 64.2%). LH concentration was significantly reduced in both MB-treated groups, but myocardial injuries were increased only in the MB + ISQ group when compared with the SS + CIR group. <b>Conclusions:</b> These results indicate that MB produces a biphasic effect on CIR, with cardiotoxic effects when administered before cardiac ischemia and cardioprotective effects when administered after ischemia but before cardiac reperfusion. |
| format | Article |
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| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-a2e2488ac847482eb10b4af8d4d7a8c22025-08-20T01:53:44ZengMDPI AGBiomedicines2227-90592024-11-011211257510.3390/biomedicines12112575Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and ReperfusionHezio Jadir Fernandes Junior0Erisvaldo Amarante de Araújo1José Antônio Machado Junior2Fabio Marinho Lutz Motta3Gabriela Ferrazzano Guarize4Lucas Chen Cheng5Junaid Tantray6Jand Venes Rolim Medeiros7Lucas Antonio Duarte Nicolau8Adriano Henrique Pereira Barbosa9Adriano Caixeta10Isadora S. Rocco11Solange Guizilini12Marcelo Pires-Oliveira13Murched Omar Taha14Afonso Caricati-Neto15Walter José Gomes16Fernando Sabia Tallo17Francisco Sandro Menezes-Rodrigues18Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilSchool of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilSchool of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilSchool of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, IndiaDepartment of Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, BrazilDepartment of Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilSchool of Medicine, Centro Universitário UNIME, Lauro de Freitas 42702-420, BA, BrazilPostgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilDepartment of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, Brazil<b>Background/Objectives:</b> Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB’s effects on the heart are unclear. Therefore, we investigated the potential cardioprotective or arrhythmogenic effects of MB in an animal model of CIR. To this end, 12–16-week-old male Wistar rats were divided into four experimental groups: (a) rats subjected to SHAM surgery with no ischemia; (b) rats subjected to CIR and treated with a vehicle (SS + CIR); and (c) rats subjected to CIR and treated with 2 mg/kg i.v. MB before ischemia (MB + ISQ) or (d) after ischemia but before reperfusion (ISQ + MB). An ECG analysis was used to evaluate the incidence of ventricular arrhythmias (VAs), atrioventricular blocks (AVBs), and lethality (LET) resulting from CIR. After CIR, rat hearts were removed for histopathological analysis and lipid hydroperoxide (LH) measurements. <b>Results:</b> The incidence of VA, AVB, and LET was significantly increased in the MB + ISQ group (VA = 100%; AVB = 100%; LET = 100%) but significantly reduced in the ISQ + MB group (VA = 42.8%; AVB = 28.5%; LET = 21.4%) compared with the SS + CIR group (VA = 85.7%; AVB = 71.4%; LET = 64.2%). LH concentration was significantly reduced in both MB-treated groups, but myocardial injuries were increased only in the MB + ISQ group when compared with the SS + CIR group. <b>Conclusions:</b> These results indicate that MB produces a biphasic effect on CIR, with cardiotoxic effects when administered before cardiac ischemia and cardioprotective effects when administered after ischemia but before cardiac reperfusion.https://www.mdpi.com/2227-9059/12/11/2575cardiac ischemia and reperfusionmyocardial injuriescardiotoxicitycardioprotectionarrhythmiasmethylene blue |
| spellingShingle | Hezio Jadir Fernandes Junior Erisvaldo Amarante de Araújo José Antônio Machado Junior Fabio Marinho Lutz Motta Gabriela Ferrazzano Guarize Lucas Chen Cheng Junaid Tantray Jand Venes Rolim Medeiros Lucas Antonio Duarte Nicolau Adriano Henrique Pereira Barbosa Adriano Caixeta Isadora S. Rocco Solange Guizilini Marcelo Pires-Oliveira Murched Omar Taha Afonso Caricati-Neto Walter José Gomes Fernando Sabia Tallo Francisco Sandro Menezes-Rodrigues Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion Biomedicines cardiac ischemia and reperfusion myocardial injuries cardiotoxicity cardioprotection arrhythmias methylene blue |
| title | Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion |
| title_full | Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion |
| title_fullStr | Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion |
| title_full_unstemmed | Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion |
| title_short | Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion |
| title_sort | cardiotoxic and cardioprotective effects of methylene blue in the animal model of cardiac ischemia and reperfusion |
| topic | cardiac ischemia and reperfusion myocardial injuries cardiotoxicity cardioprotection arrhythmias methylene blue |
| url | https://www.mdpi.com/2227-9059/12/11/2575 |
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