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
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
Affiliations
Erisvaldo Amarante de Araújo
Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, Brazil
Fernando Sabia Tallo
Discipline of Urgency and Emergency Care, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, Brazil
Alex Sandro Felisberto Oliveira
Postgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, Brazil
Gustavo Saad Silva El Toghlobi
Department of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, Brazil
Rafael Augusto Arantes
Department of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, Brazil
Rafael Balsimelli
Department of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, Brazil
Bruno Kehrwald-Balsimelli
Department of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, Brazil
Bianca Lorayne de Almeida Viana
Department of Medicine, Universidade Santo Amaro (UNISA), São Paulo 04829-300, SP, Brazil
Fernanda Sakata Matuda
Department of Medicine, Universidade Nove de Julho (UNINOVE), São Paulo 01504-001, SP, Brazil
Lucas Antonio Duarte Nicolau
Research Center on Biodiversity and Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, Brazil
Jand Venes Rolim Medeiros
Research Center on Biodiversity and Biotechnology, Universidade Federal do Delta do Parnaíba (UFDPar), Parnaíba 64202-020, PI, Brazil
Adriano Caixeta
Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, Brazil
Murched Omar Taha
Postgraduate Program in Interdisciplinary Surgical Science, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, Brazil
Walter José Gomes
Discipline of Cardiovascular Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, Brazil
Afonso Caricati-Neto
Department of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil
Francisco Sandro Menezes-Rodrigues
Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-000, SP, Brazil
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.
