Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome
Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treat...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/582 |
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| author | Erisvaldo Amarante de Araújo Fernando Sabia Tallo Alex Sandro Felisberto Oliveira Gustavo Saad Silva El Toghlobi Rafael Augusto Arantes Rafael Balsimelli Bruno Kehrwald-Balsimelli Bianca Lorayne de Almeida Viana Fernanda Sakata Matuda Lucas Antonio Duarte Nicolau Jand Venes Rolim Medeiros Adriano Caixeta Murched Omar Taha Walter José Gomes Afonso Caricati-Neto Francisco Sandro Menezes-Rodrigues |
| author_facet | Erisvaldo Amarante de Araújo Fernando Sabia Tallo Alex Sandro Felisberto Oliveira Gustavo Saad Silva El Toghlobi Rafael Augusto Arantes Rafael Balsimelli Bruno Kehrwald-Balsimelli Bianca Lorayne de Almeida Viana Fernanda Sakata Matuda Lucas Antonio Duarte Nicolau Jand Venes Rolim Medeiros Adriano Caixeta Murched Omar Taha Walter José Gomes Afonso Caricati-Neto Francisco Sandro Menezes-Rodrigues |
| author_sort | Erisvaldo Amarante de Araújo |
| collection | DOAJ |
| description | Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia–reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase–MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS. |
| first_indexed | 2024-04-24T18:31:21Z |
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| id | doaj.art-826e0c4a6b4b4cada6dda7768dff4128 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:21Z |
| publishDate | 2024-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-826e0c4a6b4b4cada6dda7768dff41282024-03-27T13:22:52ZengMDPI AGBiomedicines2227-90592024-03-0112358210.3390/biomedicines12030582Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic SyndromeErisvaldo Amarante de Araújo0Fernando Sabia Tallo1Alex Sandro Felisberto Oliveira2Gustavo Saad Silva El Toghlobi3Rafael Augusto Arantes4Rafael Balsimelli5Bruno Kehrwald-Balsimelli6Bianca Lorayne de Almeida Viana7Fernanda Sakata Matuda8Lucas Antonio Duarte Nicolau9Jand Venes Rolim Medeiros10Adriano Caixeta11Murched Omar Taha12Walter José Gomes13Afonso Caricati-Neto14Francisco Sandro Menezes-Rodrigues15Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, BrazilDiscipline of Urgency and Emergency Care, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, BrazilPostgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilDepartment of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, BrazilDepartment of Medicine, Universidade Nove de Julho (UNINOVE), São Paulo 01504-001, SP, BrazilResearch Center on Biodiversity and Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, BrazilResearch Center on Biodiversity and Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, BrazilPostgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilDiscipline of Cardiovascular Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, BrazilDepartment of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, BrazilPostgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, BrazilDefined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia–reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase–MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.https://www.mdpi.com/2227-9059/12/3/582vasoplegic syndromecardiac ischemia–reperfusionmethylene blueomeprazolecardiac arrhythmias |
| spellingShingle | Erisvaldo Amarante de Araújo Fernando Sabia Tallo Alex Sandro Felisberto Oliveira Gustavo Saad Silva El Toghlobi Rafael Augusto Arantes Rafael Balsimelli Bruno Kehrwald-Balsimelli Bianca Lorayne de Almeida Viana Fernanda Sakata Matuda Lucas Antonio Duarte Nicolau Jand Venes Rolim Medeiros Adriano Caixeta Murched Omar Taha Walter José Gomes Afonso Caricati-Neto Francisco Sandro Menezes-Rodrigues Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome Biomedicines vasoplegic syndrome cardiac ischemia–reperfusion methylene blue omeprazole cardiac arrhythmias |
| title | Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome |
| title_full | Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome |
| title_fullStr | Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome |
| title_full_unstemmed | Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome |
| title_short | Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome |
| title_sort | cardiotoxic effects produced by omeprazole and methylene blue in an animal model of cardiac ischemia and reperfusion and potential implications for the pharmacological strategy for vasoplegic syndrome |
| topic | vasoplegic syndrome cardiac ischemia–reperfusion methylene blue omeprazole cardiac arrhythmias |
| url | https://www.mdpi.com/2227-9059/12/3/582 |
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